Metabolomic profiles and differential metabolites of volatile components in Citrus aurantium Changshan-huyou pericarp during different growth and development stages.

Citrus fruits possess a distinctive aroma and flavor, with Citrus aurantium Changshan-huyou (CACH) standing out due to their considerable edible and medicinal value. However, the volatile components (VOCs) in the CACH pericarp (CP) remain underexplored. In this study, gas chromatography-mass spectrometry (GC-MS) was utilized to qualitatively analyze VOCs in 27 CP samples across different growth stages. A total of 544 VOCs were identified, including 91 terpenoids. The types, quantities and distributions of VOCs were conducted. Detailed discussions on the major terpenoids in CP were also presented. A metabolomics approach combining multivariate statistical analysis with univariate analysis was employed for screening the differential metabolites. The study provides comprehensive insights into the VOCs in CP and citrus plants. Moreover, it delivers the first in-depth analysis of differential metabolites in CP throughout the entire CACH growth and development process, laying a foundation for ongoing research and development of the VOCs in CP.

Iron Overload-induced Ferroptosis as a Target for Protection against Obliterative Bronchiolitis after Orthotopic Tracheal Transplantation in Mice.

INTRODUCTION: The major complication of Obliterative Bronchiolitis (OB) is characterized by epithelial cell loss, fibrosis, and luminal occlusion of the terminal small airways, which limits the long-term survival of the recipient after lung transplantation. However, the underlying mechanisms are still not fully clarified. This research aims to investigate whether iron overload-induced ferroptosis is involved in OB development and provide a new target for OB prevention. MATERIALS AND METHODS: Allograft orthotopic tracheal transplantation in mice was applied in our study. Ferrostatin-1 and deferoxamine were administrated to inhibit ferroptosis and get rid of ferric iron, while iron dextran was used to induce an iron overload condition in the recipient. The histological examination, luminal occlusion rate, collagen deposition, iron level, ferroptosis marker (GPX4, PTGS2), and mitochondrial morphological changes of the graft were evaluated in mice. RESULTS: Our research indicated that ferroptosis and iron overload contribute to OB development, while ferroptosis inhibition and iron chelator could reverse the changes. Iron overload exacerbated OB development after orthotopic tracheal transplantation via promoting ferroptosis. CONCLUSION: Overall, this research demonstrated that iron overload-induced ferroptosis is involved in OB, which may be a potential therapeutic target for OB after lung transplantation.

A Health-Related Quality of Life Measure for Patients Who Undergo Minimally Invasive Glaucoma Surgery.

PURPOSE: To develop a patient-reported outcome measure to assess the impact of glaucoma and treatment, including minimally invasive glaucoma surgery (MIGS). DESIGN: Observational study before and after concomitant cataract and Food and Drug Administration-approved implantable MIGS device surgery. SETTING: Survey administration was on a computer, iPad, or similar device. PATIENT POPULATION: 184 adults completed the baseline survey, 124 a survey 3 months after surgery, and 106 the 1-month test-retest reliability survey. The age range was 37 to 89 (average age = 72). Most were female (57%), non-Hispanic White (81%), and had a college degree (56%). MAIN OUTCOME MEASURES: The Glaucoma Outcomes Survey (GOS) assesses functional limitations (27 items), vision-related symptoms (7 items), psychosocial issues (7 items), and satisfaction with microinvasive glaucoma surgery (1 item). These multiple-item scales were scored on a 0 to 100 range, with a higher score indicating worse health. RESULTS: Internal consistency reliability estimates ranged from 0.75 to 0.93, and 1-month test-retest intraclass correlations ranged from 0.83 to 0.92 for the GOS scales. Product-moment correlations among the scales ranged from 0.56 to 0.60. Improvement in visual acuity in the study eye from baseline to the 3-month follow-up was significantly related to improvements in GOS functional limitations (r = 0.18, P = .0485), vision-related symptoms (r = 0.19, P = .0386), and psychosocial concerns (r = 0.18, P = .0503). Responders to treatment ranged from 17% for vision-related symptoms to 48% for functional limitations. CONCLUSIONS: This study supports using the GOS for ophthalmic procedures such as MIGS. Further evaluation of the GOS in different patient subgroups and clinical settings is needed.

[Risk factors for bronchopulmonary dysplasia in twin preterm infants: a multicenter study]. / åŒèƒŽæ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å±é™©å› ç´ åˆ†æžï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.

In Situ Photodeposition of Gold Nanoparticles with Exposed High-Activity Crystal Facets under Different Sacrificial Agents.

In situ photodeposition presents a powerful approach for integrating noble metal co-catalysts onto semiconductor surfaces. However, achieving precise control over the microstructure of the deposited co-catalyst remains a major challenge. Au nanoparticles (NPs) are deposited onto H-KCNO using HAuCl4 in the presence of various sacrificial agents in this study. Notably, the choice of sacrificial agent decisively influences the exposed crystal facets, loaded content, and particle size of the deposited Au NPs. Importantly, in situ photodeposition under an ethanol solution facilitates the exposure of the highly active (111) and (220) crystal facets of Au. The introduction of Au NPs significantly enhances photocatalytic hydrogen evolution, achieving rates of 4.93, 57.88, and 15.44 µmol/h for H-KCNO/Au-(water, ethanol, and lactic acid), respectively. The observed photocatalytic activity for hydrogen evolution indicates that the exposure of the highly active planes emerges as critical for significant performance enhancement. Photoelectrochemical and photoluminescence measurements suggest that the highly active (111) and (220) crystal facets effectively segregate sites for redox reactions, thereby impeding the recombination of photogenerated electron-hole pairs.

An antioxidant hydrogel dressing with wound pH indication function prepared based on silanized bacterial nanocellulose crosslinked with beet red pigment extract.

Maintaining wound moisture and monitoring of infection are crucial aspects of chronic wound treatment. The development of a pH-sensitive functional hydrogel dressing is an effective approach to monitor, protect, and facilitate wound healing. In this study, beet red pigment extract (BRPE) served as a native and efficient pH indicator by being grafted into silane-modified bacterial nanocellulose (BNC) to prepare a pH-sensitive wound hydrogel dressing (S-g-BNC/BRPE). FTIR confirmed the successful grafting of BRPE into the BNC matrix. The S-g-BNC/BRPE showed superior mechanical properties (0.25 MPa), swelling rate (1251 % on average), and hydrophilic properties (contact angle 21.83°). The composite exhibited a notable color change as the pH changed between 4.0 and 9.0. It appeared purple-red when the pH ranged from 4.0 to 6.0, and appeared light pink at pH 7.0 and 7.4, and appeared ginger-yellow at pH 8.0 and 9.0. Subsequently, the antioxidant activity and cytotoxicity of the composite was evaluated, its DPPH·, ABTS+, ·OH scavenging rates were 32.33 %, 19.31 %, and 30.06 %, respectively, and the cytotoxicity test clearly demonstrated the safety of the dressing. The antioxidant hydrogel dressing, fabricated with a cost-effective and easy method, not only showed excellent biocompatibility and dressing performance but could also indicated the wound state based on pH changes.

In Situ Self-Assembling Liver Spheroids with Synthetic Nanoscaffolds for Preclinical Drug Screening Applications.

Drug-induced liver injury (DILI) is one of the most common reasons for acute liver failure and a major reason for the withdrawal of medications from the market. There is a growing need for advanced in vitro liver models that can effectively recapitulate hepatic function, offering a robust platform for preclinical drug screening applications. Here, we explore the potential of self-assembling liver spheroids in the presence of electrospun and cryomilled poly(caprolactone) (PCL) nanoscaffolds for use as a new preclinical drug screening tool. This study investigated the extent to which nanoscaffold concentration may have on spheroid size and viability and liver-specific biofunctionality. The efficacy of our model was further validated using a comprehensive dose-dependent acetaminophen toxicity protocol. Our findings show the strong potential of PCL-based nanoscaffolds to facilitate in situ self-assembly of liver spheroids with sizes under 350 µm. The presence of the PCL-based nanoscaffolds (0.005 and 0.01% w/v) improved spheroid viability and the secretion of critical liver-specific biomarkers, namely, albumin and urea. Liver spheroids with nanoscaffolds showed improved drug-metabolizing enzyme activity and greater sensitivity to acetaminophen compared to two-dimensional monolayer cultures and scaffold-free liver spheroids. These promising findings highlight the potential of our nanoscaffold-based liver spheroids as an in vitro liver model for drug-induced hepatotoxicity and drug screening.

Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change.

Objective: This study aims to provide data on the effects of glucagon-like peptide 1 receptor (GLP-1R) agonists on intraocular pressure (IOP). Design: Retrospective cohort study. Subjects Participants and/or Controls: 1247 glaucoma surgery and treatment naïve eyes of 626 patients who were initiated on GLP-1R agonists compared to 1083 glaucoma surgery and treatment naïve eyes of 547 patients who were initiated on other oral antidiabetics. Methods Intervention or Testing: The University of California Health Data Warehouse was queried for patients exposed to GLP-1R agonists or other oral antidiabetics. Index date was defined as the date of first exposure to the medication. Eyes with at least one pre-exposure and one post-exposure tonometry record within 365 days of the index date were included in the analysis. Clinical and laboratory data elements were extracted from the database. Eyes were censored from the analysis upon exposure to glaucoma hypotensive medication or glaucoma surgery. ΔIOP was analyzed using a paired t-test. Regression analysis was conducted using generalized estimating equations (GEE) accounting for inter-eye correlation. Sensitivity analyses were performed to assess the robustness of the findings. Main Outcome Measures: Primary outcome measure was ΔIOP after exposure to the medication. Results: The median age of all included subjects was 66.2 years [IQR=18.3]; 607 (51.7%) were female, and 667 (56.9%) were Caucasian. Median pre-exposure IOP, HbA1c, and BMI were 15.2 mmHg [IQR=3.8], 7.5 [IQR=2.4], and 29.8 [IQR=9.4], respectively. 776 individuals (66.1%) had diabetes, with the median number of active oral antidiabetics being 1.0 [IQR=1.0], and 441 (37.5%) being insulin users. Several pre-exposure characteristics significantly differed between the GLP-1R agonist and the control group. The mean ΔIOP was -0.4±2.8 mmHg (paired t-test p<0.001) and -0.2±3.3 mmHg (paired t-test p = 0.297) in the GLP-1R agonist and other antidiabetics groups, respectively. Pre-exposure IOP was the only independent predictor of ΔIOP in multivariable GEE. Sensitivity analyses yielded similar results. Conclusions: Although GLP-1R agonists were significantly associated with a decrease in IOP in the paired analysis, they were not associated with ΔIOP in multivariable GEE. Moreover, the difference between the ΔIOP in the two groups was small. Future prospective studies following a standardized dose and delivery method may provide further insights.

Decentralized restoration of distribution systems with coupling neighboring microgrids.

In this study, a multi-agent system (MAS) is incorporated in a decentralized strategy to restore distribution systems while taking into account coupling neighboring microgrids (CNMGs). This provides modeling for renewable energy sources (RESs), electric vehicles (EVs), battery storage systems (BSS) and load. The desired and most favorable restoration path is found by the MAS, in which zone agents are dispersed across the distribution system. The MAS can also manage microgrids (MGs) overloaded as the unbalance operation of RESs, BSS, EVs, and load. This is realized by making a bridge between MGs and neighboring non-overloaded MGs. The suggested method adheres to voltage and power flow restrictions while operating according to expert system standards. The recommended approach is put to the test using a 33-bus radial distribution system. MATLAB calculations on agents and power flow are carried out in order to verify the validity of the choices made by agents. The proposed restoration plan is able to obtain the best power supply path with a low number of switching in the event of a fault so that the voltage magnitude is higher than 0.9 p.u. and free capacity is available for the distribution lines. The smart charging strategy of EVs reduces 93% of their turn off compared to the non-smart charging strategy. However, if the CNMG plan is established, all vehicles can be powered.

Uterine Artery Doppler Parameters: An Excellent Tool for Assessing Adverse Pregnancy Outcomes.

Objective: ObjectiveThis study aims to assess the utility of uterine artery Doppler parameters in predicting adverse pregnancy outcomes among pregnant women, thereby enhancing the safety of pregnancy. Methods: This study utilized a prospective observational design. A total of 142 pregnant women who underwent prenatal ultrasonography at our hospital and Wuxi Maternal and Child Health Hospital (Maternity Hospital affiliated with Jiangnan University) from May 2022 to May 2023 were included. Uterine artery Doppler ultrasonography was performed between 11-22 weeks of gestation, and the pulsatility index (PI) and resistance index (RI) were determined. Patients were followed until delivery, and outcomes were categorized into safety and risk groups. Differences in resistance index and pulsatility index between the groups were analyzed, along with their impact on adverse pregnancy outcomes. Results: Among the participants, 34 experienced adverse pregnancy outcomes. The risk group exhibited a higher resistance index and pulsatility index compared to the safety group (P < .05). The receiver operating characteristic curve analysis indicated that the resistance index had a sensitivity of 64.71% and specificity of 93.52% for adverse pregnancy outcomes (P < .05), while the sensitivity and specificity of the pulsatility index were 67.65% and 78.70%, respectively (P < .05). Within the subset of women with adverse outcomes, those with hypertensive disorders of pregnancy and/or gestational diabetes mellitus displayed the highest resistance index and pulsatility index (P < .05). Logistic regression analysis identified the resistance index and pulsatility index as independent risk factors for adverse pregnancy outcomes (P < .05). Conclusions: Uterine artery Doppler parameters demonstrate excellent predictive value for adverse pregnancy outcomes in pregnant women. This underscores their potential in enhancing prenatal care and pregnancy management strategies.

2H-Thiopyran-2-thione sulfine, a compound for converting H2S to HSOH/H2S2 and increasing intracellular sulfane sulfur levels.

Reactive sulfane sulfur species such as persulfides (RSSH) and H2S2 are important redox regulators and closely linked to H2S signaling. However, the study of these species is still challenging due to their instability, high reactivity, and the lack of suitable donors to produce them. Herein we report a unique compound, 2H-thiopyran-2-thione sulfine (TTS), which can specifically convert H2S to HSOH, and then to H2S2 in the presence of excess H2S. Meanwhile, the reaction product 2H-thiopyran-2-thione (TT) can be oxidized to reform TTS by biological oxidants. The reaction mechanism of TTS is studied experimentally and computationally. TTS can be conjugated to proteins to achieve specific delivery, and the combination of TTS and H2S leads to highly efficient protein persulfidation. When TTS is applied in conjunction with established H2S donors, the corresponding donors of H2S2 (or its equivalents) are obtained. Cell-based studies reveal that TTS can effectively increase intracellular sulfane sulfur levels and compensate for certain aspects of sulfide:quinone oxidoreductase (SQR) deficiency. These properties make TTS a conceptually new strategy for the design of donors of reactive sulfane sulfur species.

In sight the behavior of natural Bletilla striata polysaccharide hydrocolloids by molecular dynamics method.

Plant polysaccharides, distinguished by diverse glycosidic bonds and various cyclic sugar units, constitute a subclass of primary metabolites ubiquitously found in nature. Contrary to common understanding, plant polysaccharides typically form hydrocolloids upon dissolution in water, even though both excessively high and low temperatures impede this process. Bletilla striata polysaccharides (BSP), chosen for this kinetic study due to their regular repeating units, help elucidate the relationship between polysaccharide gelation and temperature. It is suggested that elevated temperatures enhance the mobility of BSP molecular chains, resulting in a notable acceleration of hydrogen bond breakage between BSP and water molecules and consequently, compromising the conformational stability of BSPs to some extent. This study unveils the unique relationship between polysaccharide dissolution processes and temperature from a kinetics perspective. Consequently, the conclusion provides a dynamical basis for comprehending the extraction and preparation of natural plant polysaccharide hydrocolloids, pharmaceuticals and related fields.

Identification and Expression Analysis of Putative Sugar Transporter Gene Family during Bulb Formation in Lilies.

Sugar transporters play important roles in plant growth and development, flowering and fruiting, as well as responses to adverse abiotic and biotic environmental conditions. Lilies (Lilium spp.) are some of the most representative ornamental bulbous flowers. Sugar metabolism is critical for bulb formation in lilies; therefore, clarifying the amount and expression pattern of sugar transporters is essential for further analyzing their roles in bulb formation. In this study, based on the transcriptome data of the Lilium Oriental hybrid 'Sorbonne' and Lilium × formolongi, a total of 69 and 41 sugar transporters were identified in 'Sorbonne' and Lilium × formolongi, respectively, by performing bioinformatics analysis. Through phylogenetic analysis, monosaccharide transporters (MSTs) can be divided into seven subfamilies, sucrose transporters (SUTs) can be divided into three subgroups, and sugars will eventually be exported transporters (SWEETs) can be divided into four clades. According to an analysis of conserved motifs, 20, 14, and 12 conserved motifs were predicted in MSTs, SUTs, and SWEETs, respectively. A conserved domain analysis showed that MSTs and SUTs contained a single domain, whereas most of the SWEETs harbored two MtN3/saliva domains, also known as a PQ-loop repeat. The LohINT1, which was predicted to have a smaller number of transmembrane structural domains, was cloned and analyzed for subcellular localization. It was found that the LohINT1 protein is mainly localized in the cell membrane. In addition, the expression analysis indicated that 22 LohMSTs, 1 LohSUTs, and 5 LohSWEETs were upregulated in 'Sorbonne' 1 day after scale detachment treatment, suggesting that they may regulate the initiation of the bulblet. A total of 10 LflMSTs, 1 LflSUTs, and 6 LflSWEETs were upregulated 4~6 months after sowing, which corresponds to the juvenile-to-adult transition phase of Lilium × formolongi, suggesting that they may also play a role in the accompanying bulb swelling process. Combined with quantitative real-time PCR (qRT-PCR) analysis, LohSTP8 and LohSTP12 were significantly overexpressed during the extremely early stage of bulblet initiation, and LflERD6.3 was significantly overexpressed during the growth of the underground bulblet, suggesting that they may be key sugar transporters in the formation of lily bulbs, which needs further functional verification.

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

The causal effect and autonomous buffering mechanisms of large-scale internal migration on carbon emissions: evidence from China.

Large-scale internal migration and unprecedented urbanization have dramatically promoted economic growth in China, resulting in a rapid surge in carbon emissions in urban areas. However, few studies have investigated the causal effect of mass internal migration on carbon emissions or examined the effects of autonomous mitigation mechanisms, such as population agglomeration and technological innovation. This study identifies the causal effect of internal migration on prefectural-level cities' carbon emissions in China by employing an instrumental variable and further investigates the buffering effect of population agglomeration and technological innovation using mediating effect models. The results show that mass internal migration has a substantial impact on increasing carbon emissions in prefectural-level cities. If the proportion of inflowed migrants rises by 1% point, prefectural-level cities' carbon emissions per capita will increase by 1.9%. A series of robustness tests confirms the result. Population migration also promotes population agglomeration and technological innovation in urban areas. Two autonomous mechanisms buffer 11.9% and 5.4% of prefectural-level cities' incremental carbon emissions per capita caused by population migration, respectively. This study highlights the crucial role of population agglomeration and technological innovation in mitigating carbon emissions in cities experiencing significant migrant inflows and provides several implications for formulating relevant policies.

Does the low carbon transition impact urban resilience? Evidence from China's pilot cities for carbon emission trading.

The low-carbon transition is a systemic economic and social change that will inevitably have an impact on many areas of the urban system. Has China's ongoing low-carbon transition impacted urban resilience (UR) systems while achieving urban energy saving and carbon emission reduction goals? This paper uses the implementation of the carbon emissions trading pilot policy (CETPP) as a "quasi-natural experiment." It evaluates the impact of the policy on UR using a difference-in-differences model based on the data of prefecture-level cities from 2008 to 2020. The study shows that pilot carbon trading policies favor UR, and the market mechanism of carbon emissions has a heterogeneous cause influence on UR. The impact of pilot carbon trading policies on UR varies according to the respective moderating effects of institutional factors, green technology innovation, industrial structure rationalization, and output effects.

Biomimetic Synthesis and Chemical Proteomics Reveal the Mechanism of Action and Functional Targets of Phloroglucinol Meroterpenoids.

Natural products perennially serve as prolific sources of drug leads and chemical probes, fueling the development of numerous therapeutics. Despite their scarcity, natural products that modulate protein function through covalent interactions with lysine residues hold immense potential to unlock new therapeutic interventions and advance our understanding of the biological processes governed by these modifications. Phloroglucinol meroterpenoids constitute one of the most expansive classes of natural products, displaying a plethora of biological activities. However, their mechanism of action and cellular targets have, until now, remained elusive. In this study, we detail the concise biomimetic synthesis, computational mechanistic insights, physicochemical attributes, kinetic parameters, molecular mechanism of action, and functional cellular targets of several phloroglucinol meroterpenoids. We harness synthetic clickable analogues of natural products to probe their disparate proteome-wide reactivity and subcellular localization through in-gel fluorescence scanning and cell imaging. By implementing sample multiplexing and a redesigned lysine-targeting probe, we streamline a quantitative activity-based protein profiling, enabling the direct mapping of global reactivity and ligandability of proteinaceous lysines in human cells. Leveraging this framework, we identify numerous lysine-meroterpenoid interactions in breast cancer cells at tractable protein sites across diverse structural and functional classes, including those historically deemed undruggable. We validate that phloroglucinol meroterpenoids perturb biochemical functions through stereoselective and site-specific modification of lysines in proteins vital for breast cancer metabolism, including lipid signaling, mitochondrial respiration, and glycolysis. These findings underscore the broad potential of phloroglucinol meroterpenoids for targeting functional lysines in the human proteome.

Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation.

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma, the leading cause of irreversible blindness. We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury. To investigate the underlying mechanism, in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor (4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole) by intravitreal injection. We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages. Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors. Furthermore, casein kinase-2 inhibition downregulated the expression of genes (Cck, Htrsa, Nef1, Htrlb, Prph, Chat, Slc18a3, Slc5a7, Scn1b, Crybb2, Tsga10ip, and Vstm21) involved in intraocular pressure elevation. Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

RNA Modifications in Cancer Stem Cell Biology.

Post-transcriptional regulation of gene expression shapes the cell state both in health and disease. RNA modifications-especially N6-methyladenosine (m6A)-have recently emerged as key players in RNA processing that depends on a sophisticated interplay between proteins of the RNA modification machinery. Importantly, the RNA epitranscriptome becomes dysregulated in cancer and promotes cancer-associated gene expression programs as well as cancer cell adaptation to the tumor microenvironment. At the top of the tumor hierarchy, cancer stem cells (CSCs) are master regulators of tumorigenesis and resistance to therapeutic intervention. Therefore, defining how RNA modifications influence the CSC state is of great importance for cancer drug development. In this chapter, we summarize the current knowledge of the roles of RNA modifications in shaping the CSC state and driving gene expression programs that confer stem-like properties to CSCs, promote CSC adaptation to the local microenvironment, and endow CSCs with metastatic potential and drug resistance.

[Advantage analysis of flow-through cell method in quality evaluation of Chinese patent medicine: a case study of Danshen Tablets].

To explore the quality consistency evaluation method for multi-component traditional Chinese medicine and establish a dissolution evaluation method suitable for the characteristics of multi-component Chinese patent medicine, this study discussed the characteristics and advantages of the flow-through cell method in the dissolution evaluation of Chinese patent medicine by comparing the impact of the small cup method and the flow-through cell method on the dissolution behavior of water-soluble and lipid-soluble major active components of Danshen Tablets. Dissolution tests were performed using the small cup method as described in the 2020 edition of the Chinese Pharmacopoeia and the newly introduced flow-through cell method(closed-loop method) with water solution containing 0.5% SDS as dissolution medium. Cumulative dissolution curves of the water-soluble component salvianolic acid B and the lipid-soluble component tanshinone Ⅱ_A in Danshen Tablets were plotted, and fitting and similarity analysis of the dissolution models was conducted to identify the characteristics and advantages of the flow-through cell method. For the small cup method, 150 mL of water containing 0.5% SDS was used as the dissolution medium, with a rotation speed of 75 r·min~(-1) and a temperature of(37±0.5) ℃, and 3 mL of samples were taken at 15, 30 min, 1, 2, and 4 h, with fresh dissolution medium added at the same temperature and volume. For the flow-through cell method, a closed-loop system was used. Danshen Tablets were placed in the flow-through cell with approximately 6.7 g of glass beads, and 150 mL of water containing 0.5% SDS was used as the dissolution medium. The flow rate was set at 20 mL·min~(-1), and the temperature and sampling were the same as the small cup method. The results showed that compared with the small cup method, the flow-through cell method had stronger discriminative power and higher sensitivity in distinguishing the dissolution behavior of the two components, and could better reflect the differences in formulation quality, especially for water-insoluble lipid-soluble components. Given that there were no essential differences in the in vitro release kinetics between the two methods, the flow-through cell method could not only replace the traditional small cup method but also better guide the formulation development and identify quality issues of formulations.