Genotype Associated with Visual Prognosis in Patients with Congenital Ectopia Lentis following Lens Surgery: a Prospective Cohort Study.

PURPOSE: To investigate the relationship between visual prognosis and genotype in patients undergoing lens surgery for congenital ectopia lentis (EL). DESIGN: Prospective clinical cohort study. METHODS: Patients with congenital EL who underwent lens removal and intraocular lens implantation received panel-based next-generation sequencing. Patients were grouped into children and adolescents/adults based on the age at surgery. The visual prognosis, including best-corrected visual acuity (BCVA) and amblyopia, was stratified into short-term and medium to long-term. RESULTS: This study included 329 probands with congenital EL, with a median age at lens surgery of 7.00 years (interquartile range [IQR] = 5.00, 12.50 years). Children with the non-FBN1 mutation exhibited inferior medium to long-term postoperative BCVA [0.26 (IQR: 0.14, 0.33) vs. 0.15 (IQR: 0.10, 0.22), P = 0.034] and a higher prevalence of amblyopia (44.4% vs. 16.8%, P = 0.012) compared to those with FBN1 mutation. Multivariable analysis showed that genotype (FBN1 vs. non-FBN1 mutation) was significantly associated with medium to long-term postoperative BCVA (b = -0.128, 95% CI -0.214 to -0.042, P = 0.004) and amblyopia (OR = 0.20, 95% CI 0.05 to 0.78, P = 0.020) in children. Further classification of FBN1 genotype did not yield significant correlations with visual prognosis. However, no significant correlation was observed between genotype and short-term visual prognosis in the children. Children with less severe EL (OR = 0.13, 95% CI 0.02 to 0.85, P = 0.033) had lower risks of amblyopia in the short-term follow-up. For adolescent and adult patients with congenital EL, those with poor preoperative BCVA and long axial length should be informed of suboptimal visual prognosis. CONCLUSIONS: Genotype significantly influences the medium to long-term visual prognosis in children with congenital EL. Genotype, along with pre-operative BCVA, may assist in establishing reasonable expectations for patients regarding their visual outcomes after the lens surgery.

A class of geranylquinol-derived polycyclic meroterpenoids from Arnebia euchroma against heart failure by reducing excessive autophagy and apoptosis in cardiomyocytes.

Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis.

Asymmetric Microenvironment Tailoring Strategies of Atomically Dispersed Dual-Site Catalysts for Oxygen Reduction and CO2 Reduction Reactions.

Dual-atom catalysts (DACs) with atomically dispersed dual-sites, as an extension of single-atom catalysts (SACs), have recently become a new hot topic in heterogeneous catalysis due to their maximized atom efficiency and dual-site diverse synergy, because the synergistic diversity of dual-sites achieved by asymmetric microenvironment tailoring can efficiently boost the catalytic activity by optimizing the electronic structure of DACs. Here, this work first summarizes the frequently-used experimental synthesis and characterization methods of DACs. Then, four synergistic catalytic mechanisms (cascade mechanism, assistance mechanism, co-adsorption mechanism and bifunction mechanism) and four key modulating methods (active site asymmetric strategy, transverse/axial-modification engineering, distance engineering and strain engineering) are elaborated comprehensively. The emphasis is placed on the effects of asymmetric microenvironment of DACs on oxygen/carbon dioxide reduction reaction. Finally, some perspectives and outlooks are also addressed. In short, the review summarizes a useful asymmetric microenvironment tailoring strategy to speed up synthesis of high-performance electrocatalysts for different reactions.

The effects of ß-hydroxy-ß-methylbutyrate or HMB-rich nutritional supplements on sarcopenia patients: a systematic review and meta-analysis.

Background: Sarcopenia is a progressive, systemic skeletal muscle disorder. Resistance exercise and physical activity have been proven effective in its treatment, but consensus on pharmacological interventions has not yet been reached in clinical practice. ß-Hydroxy-ß-methylbutyrate (HMB) is a nutritional supplement that has demonstrated favorable effects on muscle protein turnover, potentially contributing to beneficial impacts on sarcopenia. Aim: To assess the potential positive effects of HMB or HMB-containing supplements on individuals with sarcopenia, a systematic review and meta-analysis was conducted. Methods: A systematic review and meta-analysis were conducted on randomized controlled trials (RCTs) examining the treatment of sarcopenia with HMB. Two assessors independently conducted screening, data extraction, and bias risk assessment. Outcome data were synthesized through a random-effects model in meta-analysis, using the mean difference (MD) as the effect measure. Results: A meta-analysis was conducted on six studies. HMB or HMB-rich nutritional supplements showed a statistically significant difference in Hand Grip Strength (HGS) for sarcopenia patients [MD = 1.26, 95%CI (0.41, 2.21), p = 0.004], while there was no statistically significant difference in Gait Speed (GS) [MD = 0.04, 95%CI (-0.01, 0.08), p = 0.09], Fat Mass (FM) [MD = -0.18, 95%CI (-0.38, 0.01), p = 0.07], Fat-Free Mass (FFM) [MD = 0.09, 95%CI (-0.23, 0.42), p = 0.58], and Skeletal Muscle Index (SMI) [MD = 0.01, 95%CI (-0.00, 0.01), p = 0.13]. Conclusion: HMB or HMB-rich nutritional supplements are beneficial for muscle strength in sarcopenia patients. However, there is limited evidence demonstrating significant effects on both muscle strength and physical performance in sarcopenia individuals. HMB may be considered as a treatment option for sarcopenia patients. Systematic review registration: CRD42024512119.

Antibacterial Janus cellulose/MXene paper with exceptional salt rejection for sustainable and durable solar-driven desalination.

The scarcity of freshwater resources and increasing demand for drinking water have driven the development of durable and sustainable desalination technologies. Although MXene composites have shown promise due to their excellent photothermal conversion and high thermal conductivity, their high hydrophilicity often leads to salt precipitation and low durability. In this study, we present a novel Cellulose (CF)/MXene paper with a Janus hydrophobic/hydrophilic configuration for long-term and efficient solar-driven desalination. The paper features a dual-layer structure, with the upper hydrophobic layer composed of CF/MXene paper exhibiting convexness to serve as a photothermal layer with exceptional salt rejection properties. Simultaneously, the bottom porous layer made of CF acts as an efficient thermal insulation. This unique design effectively minimizes heat loss and facilitates efficient water transportation. The Janus CF/MXene paper demonstrates a high evaporation rate of 1.11 kg m-2h-1 and solar thermal conversion efficiency of 82.52 % under 1 sun irradiation. Importantly, even after 2500 h of operation in a simulated seawater environment, the paper maintains a stable evaporation rate without significant salt deposition and biodegradation due to an antibacterial rate exceeding 90 %. These findings highlight the potential of the Janus CF/MXene paper for scalable manufacturing and practical applications in solar-driven desalination.

Transcriptomic Insights into Molecular Response of Butter Lettuce to Different Light Wavelengths.

Lettuce is a widely consumed leafy vegetable; it became popular due to its enhanced nutritional content. Recently, lettuce is also regarded as one of the model plants for vegetable production in plant factories. Light and nutrients are essential environmental factors that affect lettuce growth and morphology. To evaluate the impact of light spectra on lettuce, butter lettuce was grown under the light wavelengths of 460, 525, and 660 nm, along with white light as the control. Plant morphology, physiology, nutritional content, and transcriptomic analyses were performed to study the light response mechanisms. The results showed that the leaf fresh weight and length/width were higher when grown at 460 nm and lower when grown at 525 nm compared to the control treatment. When exposed to 460 nm light, the sugar, crude fiber, mineral, and vitamin concentrations were favorably altered; however, these levels decreased when exposed to light with a wavelength of 525 nm. The transcriptomic analysis showed that co-factor and vitamin metabolism- and secondary metabolism-related genes were specifically induced by 460 nm light exposure. Furthermore, the pathway enrichment analysis found that flavonoid biosynthesis- and vitamin B6 metabolism-related genes were significantly upregulated in response to 460 nm light exposure. Additional experiments demonstrated that the vitamin B6 and B2 content was significantly higher in leaves exposed to 460 nm light than those grown under the other conditions. Our findings suggested that the addition of 460 nm light could improve lettuce's biomass and nutritional value and help us to further understand how the light spectrum can be tuned as needed for lettuce production.

Widespread and active piezotolerant microorganisms mediate phenolic compound degradation under high hydrostatic pressure in hadal trenches.

Phenolic compounds, as well as other aromatic compounds, have been reported to be abundant in hadal trenches. Although high-throughput sequencing studies have hinted at the potential of hadal microbes to degrade these compounds, direct microbiological, genetic and biochemical evidence under in situ pressures remain absent. Here, a microbial consortium and a pure culture of Pseudomonas, newly isolated from Mariana Trench sediments, efficiently degraded phenol under pressures up to 70 and 60 MPa, respectively, with concomitant increase in biomass. By analyzing a high-pressure (70 MPa) culture metatranscriptome, not only was the entire range of metabolic processes under high pressure generated, but also genes encoding complete phenol degradation via ortho- and meta-cleavage pathways were revealed. The isolate of Pseudomonas also contained genes encoding the complete degradation pathway. Six transcribed genes (dmpKLMNOPsed) were functionally identified to encode a multicomponent hydroxylase catalyzing the hydroxylation of phenol and its methylated derivatives by heterogeneous expression. In addition, key catabolic genes identified in the metatranscriptome of the high-pressure cultures and genomes of bacterial isolates were found to be all widely distributed in 22 published hadal microbial metagenomes. At microbiological, genetic, bioinformatics, and biochemical levels, this study found that microorganisms widely found in hadal trenches were able to effectively drive phenolic compound degradation under high hydrostatic pressures. This information will bridge a knowledge gap concerning the microbial aromatics degradation within hadal trenches. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00224-2.

A neural-mast cell axis regulates skin microcirculation in diabetes.

Changes in microcirculation lead to the progression of organ pathology in diabetes. Although neuroimmune interactions contribute to a variety of conditions, it is still unclear whether abnormal neural activities affect microcirculation related to diabetes. Using laser speckle contrast imaging, we examined the skin of patients with type 2 diabetes and found that their microvascular perfusion was significantly compromised. This phenomenon was recapitulated in a high-fat-diet-driven murine model of type 2 diabetes-like disease. In this setting, although both macrophages and mast cells were enriched in the skin, only mast cells and associated degranulation were critically required for the microvascular impairment. Sensory neurons exhibited enhanced TRPV1 activities, which triggered mast cells to degranulate and compromise skin microcirculation. Chemical and genetic ablation of TRPV1+ nociceptors robustly improve skin microcirculation status. Substance P (SP) is a neuropeptide and was elevated in the skin and sensory neurons in the context of type 2 diabetes. Exogenous administration of SP resulted in impaired skin microcirculation, whereas neuronal knockdown of SP dramatically prevented mast cell degranulation and consequently improved skin microcirculation. Overall, our findings indicate a neural-mast cell axis underlying skin microcirculation disturbance in diabetes and shed light on neuroimmune therapeutics for diabetes-related complications.

Evaluation of Renal Microhemodynamics Heterogeneity in Different Strains and Sexes of Mice.

Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducted an investigation into the variations in renal function and related biological oscillators. Using the genetically diverse mouse models BALB/c, C57BL/6, and Kunming, which serve as established proxies for the study of renal pathophysiology, we implemented laser Doppler flowmetry conjoined with wavelet transform analyses to interrogate dynamic renal microcirculation. Creatinine, urea, uric acid, glucose, and cystatin C levels were quantified to investigate potential divergences attributable to sex and genetic lineage. Our findings reveal marked sexual dimorphism in metabolite concentrations, as well as strain-specific variances, particularly in creatinine and cystatin C levels. Through the combination of Mantel tests and Pearson correlation coefficients, we delineated the associations between renal functional metrics and microhemodynamics, uncovering interactions in female BALB/c mice for creatinine and uric acid, and in male C57BL/6 mice for cystatin C. Histopathologic examination confirmed an augmented microvascular density in female mice and elucidating variations in the expression of estrogen receptor ß among the strains. These data collectively highlight the influence of both sex and genetic constitution on renal microcirculation, providing an understanding that may inform the etiologic exploration of renal ailments.

Dataset on cardiac structural and functional parameters in TMAO-challenged mouse.

Trimethylamine-N-oxide (TMAO) is a gut-derived metabolite formed from dietary choline and l-carnitine, known to impede cholesterol metabolism and is implicated in the pathogenesis of thrombosis and atherosclerosis, contributing to the etiology of cardiovascular diseases. We present a dataset derived from an experimental study designed to elucidate the cardiotoxic effects of TMAO. This dataset encompasses echocardiographic assessments from two cohorts of mice: one subjected to a 6-week regimen of 20 mg/kg/day TMAO injections (n = 16) and a control group (n = 18). Each subject's echocardiographic dataset comprises six high-resolution TIFF images, capturing both B-type and M-mode views in standard echocardiographic planes, along with two additional M-mode images enriched with analysed cardiac functional data. Complementing these images, a CSV-formatted report details critical cardiac parameters, including heart rate, ejection fraction, and fractional shortening, among others. In a novel approach to enhance data integrity and permit tailored analyses, we provide the original output files from the echocardiography apparatus, which researchers can reprocess using dedicated analysis software. This dataset is anticipated to be instrumental in advancing our understanding of the mechanistic links between TMAO exposure and cardiac dysfunction.

High-Entropy Lithium Niobate Nanocubes for Photocatalytic Water Splitting under Visible Light.

The vast compositional space available in high-entropy oxide semiconductors offers unique opportunities for electronic band structure engineering in an unprecedented large room. In this work, with wide band gap semiconductor lithium niobate (LiNbO3) as a model system, we show that the substitutional addition of high-entropy metal cation mixtures within the Nb sublattice can lead to the formation of a single-phase solid solution featuring a substantially narrowed band gap and intense broadband visible light absorption. The resulting high-entropy LiNbO3 [denoted as Li(HE)O3] crystallizes as well-faceted nanocubes; atomic-resolution imaging and elemental mapping via transmission electron microscopy unveil a distinct local chemical complexity and lattice distortion, characteristics of high-entropy stabilized solid solution phases. Because of the presence of high-entropy stabilized Co2+ dopants that serve as active catalytic sites, Li(HE)O3 nanocubes can accomplish the visible light-driven photocatalytic water splitting in an aqueous solution containing methanol as a sacrificial electron donor without the need of any additional co-catalysts.

Functional Identification of HhUGT74AG11-A Key Glycosyltransferase Involved in Biosynthesis of Oleanane-Type Saponins in Hedera helix.

Hedera helix is a traditional medicinal plant. Its primary active ingredients are oleanane-type saponins, which have extensive pharmacological effects such as gastric mucosal protection, autophagy regulation actions, and antiviral properties. However, the glycosylation-modifying enzymes responsible for catalyzing oleanane-type saponin biosynthesis remain unidentified. Through transcriptome, cluster analysis, and PSPG structural domain, this study preliminarily screened four candidate UDP-glycosyltransferases (UGTs), including Unigene26859, Unigene31717, CL11391.Contig2, and CL144.Contig9. In in vitro enzymatic reactions, it has been observed that Unigene26859 (HhUGT74AG11) has the ability to facilitate the conversion of oleanolic acid, resulting in the production of oleanolic acid 28-O-glucopyranosyl ester. Moreover, HhUGT74AG11 exhibits extensive substrate hybridity and specific stereoselectivity and can transfer glycosyl donors to the C-28 site of various oleanane-type triterpenoids (hederagenin and calenduloside E) and the C-7 site of flavonoids (tectorigenin). Cluster analysis found that HhUGT74AG11 is clustered together with functionally identified genes AeUGT74AG6, CaUGT74AG2, and PgUGT74AE2, further verifying the possible reason for HhUGT74AG11 catalyzing substrate generalization. In this study, a novel glycosyltransferase, HhUGT74AG11, was characterized that plays a role in oleanane-type saponins biosynthesis in H. helix, providing a theoretical basis for the production of rare and valuable triterpenoid saponins.

Tiny clue reveals the general trend: a bibliometric and visualized analysis of renal microcirculation.

BACKGROUND: Renal microcirculation plays a pivotal role in kidney function by maintaining structural and functional integrity, facilitating oxygen and nutrient delivery, and waste removal. However, a thorough bibliometric analysis in this area remains lacking. Therefore, we aim to provide valuable insights through a bibliometric analysis of renal microcirculation literature using the Web of Science database. METHODS: We collected renal microcirculation-related publications from the Web of Science database from January 01, 1990, to December 31, 2022. The co-authorship of authors, organizations, and countries/regions was analyzed with VOSviewer1.6.18. The co-occurrence of keywords and co-cited references were analyzed using CiteSpace6.1.R6 software to generate visualization maps. Additionally, burst detection was applied to keywords and cited references to forecast research hotspots and future trends. RESULTS: Our search yielded 7462 publications, with the American Journal of Physiology-Renal Physiology contributing the most articles. The United States, Mayo Clinic, and Lerman Lilach O emerged with the highest publication count, indicating their active collaborations. 'Type 2 diabetes' was the most significant keyword cluster, and 'diabetic kidney disease' was the largest cluster of cited references. 'Cardiovascular outcome' and 'diabetic kidney diseases' were identified as keywords in their burst period over the past three years. CONCLUSION: Our bibliometric analysis illuminates the contours of nephrology and microcirculation research, revealing a landscape ripe for challenges and the seeds of future scientific innovation. While the trends discerned from the literature emerging opportunities in diagnostic innovation, renal microcirculation research, and precision medicine interventions, their translation to clinical practice is anticipated to be a deliberate process.

Photocatalytic Hydrogen Production from Pure Water Using a IEF-11/g-C3N4 S-Scheme Heterojunction.

Construction of S-scheme heterojunction offers a promising way to enhance the photocatalytic performance of photocatalysts for converting solar energy into chemical energy. However, the photocatalytic H2 production in pure water without sacrificial agents is still a challenge. Herein, the IEF-11 with the best photocatalytic H2 production performance in MOFs and suitable band structure was selected and firstly constructed with g-C3N4 to obtain a S-scheme heterojunction for photocatalytic H2 production from pure water. As a result, the novel IEF-11/g-C3N4 heterojunction photocatalysts exhibited significantly improved photocatalytic H2 production performance in pure water without any sacrificial agent, with a rate of 576 µmol/g/h, which is about 8 times than that of g-C3N4 and 23 times of IEF-11. The novel IEF-11/g-C3N4 photocatalysts also had a photocatalytic H2 production rate of up to 92 µmol/g/h under visible light and a good photocatalytic stability. The improved performance can be attributed to the efficient separation of photogenerated charge carriers, faster charge transfer efficiency and longer photogenerated carrier lifetimes, which comes from the forming of S-scheme heterojunction in the IEF-11/g-C3N4 photocatalyst. This work is a promising guideline for obtaining MOF-based or g-C3N4-based photocatalysts with great photocatalytic water splitting performance.

Ranolazine for improving coronary microvascular function in patients with nonobstructive coronary artery disease: a systematic review and meta-analysis with a trial sequential analysis of randomized controlled trials.

Background: Microvascular dysfunction in patients with nonobstructive coronary artery disease is increasingly being recognized as an important health issue. This systematic review and meta-analysis evaluated the effectiveness of ranolazine, an antianginal agent, in improving coronary microvascular function. Methods: We conducted a comprehensive literature search of the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, the Chinese BioMedical Literature Database, and gray literature databases until September 30, 2023. The included studies were randomized controlled trials (RCTs) published in the English or Chinese languages that screened for eligibility using two independent investigators. Risk of bias was evaluated with the Cochrane Collaboration tool. Subgroup and sensitivity analyses were used to identify sources of heterogeneity. Meta-analysis was performed using RevMan version 5.4 (Cochrane) and Stata version 16.0 (StataCorp). Results: From 1,470 citations, 8 RCTs involving 379 participants were included in this analysis. Our findings showed that ranolazine increased coronary flow reserve (CFR) over an 8 to 12-week follow-up period [standardized mean difference =1.16; 95% confidence interval (CI): 0.4-1.89; P=0.002]. Ranolazine increased the global myocardial perfusion reserve index (MPRI) [weighted mean difference (WMD) =0.18; 95% CI: 0.07-0.29; P=0.002] and the midsubendocardial MPRI (WMD =0.10; 95% CI: 0.02-0.19; P=0.02). Moreover, ranolazine improved 3 of the 5 Seattle Angina Questionnaire scores, namely, physical functioning (WMD =4.89; 95% CI: 0.14 to 9.64; P=0.04), angina stability (WMD =17.31; 95% CI: 7.13-27.49; P=0.0009), and quality of life (WMD =10.11; 95% CI: 3.57-16.65; P=0.0003). Trial sequential analysis showed that the meta-analysis of angina stability and quality of life scores had a sufficient sample size and statistical power. Conclusions: Our analysis suggests that ranolazine is associated with improvements in CFR, myocardial perfusion, and the Seattle Angina Questionnaire scores in patients with nonobstructive coronary artery disease. However, further large-scale RCTs with long-term follow-up are recommended to validate these findings and provide a more comprehensive understanding of the effects of ranolazine on coronary microvascular function.

Hemicellulose-based nanoaggregate-incorporated biocompatible hydrogels with enhanced mechanical properties and sustained controlled curcumin release behaviors.

Local drug delivery has generated considerable interest due to its controlled and sustained drug release at the target site on demand. Nanoaggregate-incorporated composite hydrogels are desirable as local drug delivery systems; however, it is difficult to achieve sustained and controlled hydrophobic drug release and superior mechanical properties in one system. Herein, a "smart" composite hydrogel was synthesized by incorporating hemicellulose-based nanoaggregates into a double network consisting of alginate/Ca2+ and polyacrylic acid-co-dimethylaminoethyl methacrylate [P(AA-co-DMAEMA)]. Hemicellulose-based nanoaggregates were assembled from xylan-rich hemicellulose laurate methacrylate (XH-LA-MA) polymers and entrapped into the hydrogel framework via chemical fixation. Another composite hydrogel with physically embedded hemicellulose laurate (XH-LA) nanoaggregates was prepared as a comparison. Accordingly, covalently cross-linked XH-LA-MA nanoaggregates in hydrogels resulted in a denser pore structure and reinforced mechanical properties. Nanoaggregate diffusion analysis revealed that covalent bonding between the nanoaggregates and the hydrogel framework contributed to prolonged diffusion behavior. Curcumin (Cur)-loaded XH-LA-MA composite hydrogels enabled sustained Cur release in simulated body fluid and showed stimulus responsiveness toward ethylenediaminetetraacetic acid (EDTA) and/or glutathione (GSH). All the composite hydrogels were biocompatible, as verified by Cell Counting Kit-8 (CCK-8) assay against NIH/3T3 cells. These composite hydrogels hold great potential as a promising dosage form for biomedical applications.

Dynamic immuno-nanomedicines in oncology.

Anti-cancer therapeutics have achieved significant advances due to the emergence of immunotherapies that rely on the identification of tumors by the patients' immune system and subsequent tumor eradication. However, tumor cells often escape immunity, leading to poor responsiveness and easy tolerance to immunotherapy. Thus, the potentiated anti-tumor immunity in patients resistant to immunotherapies remains a challenge. Reactive oxygen species-based dynamic nanotherapeutics are not new in the anti-tumor field, but their potential as immunomodulators has only been demonstrated in recent years. Dynamic nanotherapeutics can distinctly enhance anti-tumor immune response, which derives the concept of the dynamic immuno-nanomedicines (DINMs). This review describes the pivotal role of DINMs in cancer immunotherapy and provides an overview of the clinical realities of DINMs. The preclinical development of emerging DINMs is also outlined. Moreover, strategies to synergize the antitumor immunity by DINMs in combination with other immunologic agents are summarized. Last but not least, the challenges and opportunities related to DINMs-mediated immune responses are also discussed.

Overview of Sample Delivery Methods for Serial Crystallography / 生物化学与生物物理进展

The sample delivery method is one of the key steps in implementing serial femtosecond crystallography research using X-ray free-electron lasers. Serial femtosecond crystallography can effectively capture the ultrafast dynamic processes of biological molecules, such as protein conformational changes and intermediate states in chemical reactions. It is of great significance for scientists to better understand the structure and function of biological molecules, reveal the mechanisms of life activities, and provide important technical means for drug development and biotechnology. When conducting experiments at X-ray free-electron laser beamline station, it is crucial to transport the samples to the region where it interacts with the free-electron laser pulses. The choice of suitable sample delivery method plays a decisive role in the sample consumption and experimental efficiency, and it is also an important factor for the success or failure of the experiment. This article reviews the latest research progress and future development directions of sample delivery methods in serial crystallography. It also introduces commonly used sample delivery methods and their applicable ranges, aiming to provide reference and guidance for scientists engaged in serial crystallography research. The sample transport methods of free electron lasers mainly include liquid injection and fixed target sample transport. The liquid injection method is achieved through various liquid sample injectors. The aqueous solution is driven by a peristaltic pump on high performance liquid chromatography (HPLC) into a sample storage, and the aqueous solution pushes the piston in the sample storage to extrude the sample solution into the sample transport pipeline, and finally sprays it out through the nozzle to reach the XFEL interaction region. For micro-nano crystals,3 preparation methods are introduced, including free interface diffusion method, seeding method, and batch crystallization, and characterization methods are also introduced. For the requirements of high sample transmission efficiency and low sample consumption, a gas-based liquid flow transport method is introduced, which is based on the principle of focusing the sample jet by coaxial gas to form a jet with a small diameter and fast flow rate. At the same time, the extended double flow focusing nozzle and mixed injection nozzle are briefly described. For samples in viscous media, a high viscosity liquid injection device is introduced, and the advantages and disadvantages of different media are explained and exemplified. In addition, the principle and example of electrostatic spinning injector and piezoelectric driven droplet injection technology applied to low-velocity serial crystallography experiments are also introduced. For the above liquid injection methods, a characterization method using a coaxial microscope or side-view microscope to measure the diameter and stable length of the liquid flow is introduced. Compared with the liquid injection method, the fixed target method is to fix the crystal on a support chip with a periodic array structure, and collect data through scanning. The working principle, sample environment, support materials, etc. of the fixed target method are briefly introduced in the article. With the advancement and development of technologies such as free electron lasers and detectors, various sampling methods for serial crystallography are constantly being innovated and optimized. By selecting appropriate sample delivery methods, it will be possible to improve experimental efficiency, reduce sample consumption, and open up new possibilities for researchers in the field of structural biology of biomacromolecules.

Harnessing the benefits of glycine supplementation for improved pancreatic microcirculation in type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is predominantly managed using insulin replacement therapy, however, pancreatic microcirculatory disturbances play a critical role in T1DM pathogenesis, necessitating alternative therapies. This study aimed to investigate the protective effects of glycine supplementation on pancreatic microcirculation in T1DM. Streptozotocin-induced T1DM and glycine-supplemented mice (n = 6 per group) were used alongside control mice. Pancreatic microcirculatory profiles were determined using a laser Doppler blood perfusion monitoring system and wavelet transform spectral analysis. The T1DM group exhibited disorganized pancreatic microcirculatory oscillation. Glycine supplementation significantly restored regular biorhythmic contraction and relaxation, improving blood distribution patterns. Further-more, glycine reversed the lower amplitudes of endothelial oscillators in T1DM mice. Ultrastructural deterioration of islet microvascular endothelial cells (IMECs) and islet microvascular pericytes, including membrane and organelle damage, collagenous fiber proliferation, and reduced edema, was substantially reversed by glycine supplementation. Additionally, glycine supplementation inhibited the production of IL-6, TNF-α, IFN-γ, pro-MMP-9, and VEGF-A in T1DM, with no significant changes in energetic metabolism observed in glycine-supplemented IMECs. A statistically significant decrease in MDA levels accompanied by an increase in SOD levels was also observed with glycine supplementation. Notably, negative correlations emerged between inflammatory cytokines and microhemodynamic profiles. These findings suggest that glycine supplementation may offer a promising therapeutic approach for protecting against pancreatic microcirculatory dysfunction in T1DM.