Search

Two new cucurbitane-type triterpenoid saponins, 2,20 β ,22 β -trihydroxy-16 α ,23( R )-epoxycucurbita-1,5,24-triene-3,11-dione 2- O - β -D-glucopyranoside ( 1 ), 2,20 β ,22 α -trihydroxy-16 α ,23( S )-epoxycucurbita-1,5,11,24-tetraene-3-one 2- O - β -D-glucopyranoside ( 2 ) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10  μ M against paracetamol-induced HepG2 cell damage.

Three new flavonoids including two isoflavanones sophortones A and B ( 1 and 2 ), and one chalcone sophortone C ( 3 ) were isolated from the roots of Sophora tonkinensis . Their structures were established by UV, IR, HRESIMS, and NMR data. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations.

Background: Growing evidence emphasizes the importance of xanthophyll carotenoids and omega-3 fatty acids in eye health. However, the beneficial effects of such supplementation have not been thoroughly discussed among adults with high screen exposure. Current trial evidence on lutein bioavailability is contradictory, and the interactions of dietary intervention with host-related factors remain elusive. This study aims to investigate the comparative effectiveness of supplementation with macular xanthophylls and omega-3 fatty acids on macular pigment optical density (MPOD) and visual function, access the bioavailability of free lutein and lutein ester, and explore the complex interplay between genetic variations, intestinal microbiota, and the dietary intervention in Chinese adults with long-term exposure to digital devices., Methods: The Lutein, Zeaxanthin, and Omega-3 (LZO) clinical trial is a 24-week multicenter, randomized, double-blind, placebo-controlled trial of 600 participants recruited from research centers, universities, and communities. Individuals are eligible to participate if they are aged over 18 years and use digital devices for over 8 h daily in the last 2 years, and will be randomized to six arms. A total of three visits will be scheduled at baseline, 12 and 24 weeks. The primary outcome is the change in MPOD over the 24-week intervention. The secondary outcomes are changes in visual function (visual acuity, best-corrected visual acuity, contrast and glare sensitivity, critical flicker fusion, reaction time, visuognosis persistence, symptoms and signs of dry eye, retinal thickness, and optical quality), and changes in serum lutein and zeaxanthin concentrations, and erythrocyte membrane omega-3 fatty acids. Genetic variations will be determined using genome-wide genotyping at baseline. 16S rRNA gene sequencing will be utilized to assess microbiome compositional changes before and after intervention., Discussion: The trial is anticipated to establish early interventions to prevent photochemical ocular damage and delay the onset of vision impairment in young adults with long-term repeated exposure to screen-based electronic devices, and provide valuable insights for the development of precision nutrition strategies for maintaining eye health., Clinical Trial Registration: www.clinicaltrials.in.th, Identifier, TCTR20220904002., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Ma, Li, Pei, Wang, Li, Yang, Liu, Tang, Hao, Jiang, Fu, Xiao, Wang, Cui, Su, Bai, Tang, Wang, Shan, Jiang, Deng, Kong, Hui and Ma.)

To analyze the causes of ozone pollution in the Pearl River Delta （PRD） Region during the summer and autumn transition seasons, a case study was carried out in Guangzhou, which is located in the center of the PRD Region, to analyze the ozone photochemical production and destruction pathways as well as emission reduction scenarios using a box model based on comprehensive observation. The results showed that the stagnant meteorological conditions and high temperature during the observation period were suitable for the photochemical production of ozone, which led to widespread and prolonged ozone pollution. Aromatic hydrocarbons （AHs） contributed the most to the ozone formation potential （OFP）, and m / p -xylene, toluene, and o -xylene were the major three VOC species contributing to the OFP. Box model analysis revealed that the averaged net O 3 production rate during the polluted period was 23.2×10 -9 h -1 and the peak reached 39.2×10 -9 h -1 . The HO 2 ·+NO and NO 2 +·OH reaction pathways contributed the most to the local photochemical ozone production （51.2%） and destruction （47.0%）, respectively. Observed ozone concentration was primarily controlled by both the local photochemical O 3 production and the export-dominated transport. The RIR and EKMA analyses showed that O 3 formation in Guangzhou during the summer-autumn transition seasons was mainly a VOC-limited regime and AHs showed the greatest sensitivity to O 3 production. Toluene, m / p -xylene, o -xylene, n -butane, and propylene were the five key components affecting O 3 generation. The analysis of reduction scenarios showed that reducing anthropogenic VOC emissions was the most favorable way to reduce O 3 concentrations； however, if NO x emission was controlled after reducing VOCs, the O 3 concentration would rebound in a short time. Our results suggested that the synergistic reduction of VOCs and NO x while mainly focusing on VOCs alleviation should be implemented to continuously reduce ozone concentrations in the future.

Background/purpose: Understanding the relationship between maxillary sinus and posterior root apices is critical in preventing dental treatment complications. This study aimed to analyze and showcase the relationship between the posterior root apices and the maxillary sinus floor, the distance to the buccal cortical bone, and their correlation with age, gender, and sides., Materials and Methods: Cone-beam computed tomography images were collected from 94 patients with a total of 478 maxillary posterior teeth and 997 roots. The shortest distance from root apices to the closest border of maxillary sinus and the outer buccal cortical bone margin were measured and grouped for statistical analysis for the differences ( P  < 0.05)., Results: The root apices of maxillary molars and single-rooted second premolars were located closer to the maxillary sinus compared to first premolars ( P  < 0.01). The buccal root of two-rooted first premolar had the shortest horizontal distance to the buccal cortical bone among all roots ( P  < 0.01). The lowest position of the maxillary sinus floor was mostly located at the palatal side ( P  < 0.01) and between the buccal and palatal root apices ( P  < 0.01) in the maxillary premolars and molars, respectively. Increasing age would lead to longer distances between the root apices and the maxillary sinus ( P  < 0.01). Additionally, male patients had thicker buccal cortical bone than female patients ( P  < 0.01)., Conclusion: Different tooth positions, age, and gender significantly impact the relationships between root apices and the maxillary sinus and buccal cortical plates, informing patient-centered and individually tailored approaches for more effective and safer surgical endodontic treatment., Competing Interests: All authors declare no conflict of interest related to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Light-emitting diode (LED) is commonly used in lighting and digital devices in modern life, which delivers higher levels of blue light than other light sources. Previous work indicated that exposure to blue lights increases serum oxidative stress and affects hepatic functions in animals. However, the detailed hepatic pathogenesis caused by blue lights remains largely elusive. This study investigated the characteristics of hepatic injuries caused by LED light exposure in a mouse model. C57BL/6 mice were exposed the LED lights at 1000 lux, 12 h per day for 45 days or at 4500 lux, 1 h per day for 7 days. The mice were aged 8 weeks or 36 weeks in both genders and maintained under a 12 h light/dark cycle without alteration of diet pattern. Liver tissue sections were obtained for hematoxylin and eosin (H&E) and immunohistochemical staining. The mice with 1000 lux exposure displayed severe liver injuries, including inflammation, ballooning, and pyknosis, which were found to a lesser extent in the 4500 lux mice, and aging aggravated the hepatic injuries. The hepatocellular ballooning was found more severe in the males than the females. In contrast, the females expressed the F4/80 and TNF-α inflammatory markers more evidently. Taken together, LED light exposure may have detrimental effects on liver health, particularly in vulnerable groups such as the elderly and the females with excessive exposure to LED lights, even if they maintain a normal diet and regular light/dark cycles. The potential risk should be considered by both the clinicians and the public., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Han-Hsin Chang reports financial support was provided by National Science and Technology Council. Han-Hsin Chang reports a relationship with National Science and Technology Council that includes: travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13 C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Radiofrequency ablation (RFA) is the treatment of choice for atrial fibrillation (AF). Additionally, the utilization of 3D printing for cardiac models offers an in-depth insight into cardiac anatomy and cardiovascular diseases. The study aims to evaluate the clinical utility and outcomes of RFA following in vitro visualization of the left atrium (LA) and pulmonary vein (PV) structures via 3D printing (3DP). Between November 2017 and April 2021, patients who underwent RFA at the First Affiliated Hospital of Xinxiang Medical University were consecutively enrolled and randomly allocated into two groups: the 3DP group and the control group, in a 1:1 ratio. Computed tomography angiography (CTA) was employed to capture the morphology and diameter of the LA and PV, which facilitated the construction of a 3D entity model. Additionally, surgical procedures were simulated using the 3D model. Parameters such as the duration of the procedure, complications, and rates of RFA recurrence were meticulously documented. Statistical analysis was performed using the t-test or Mann-Whitney U test to evaluate the differences between the groups, with a P-value of less than 0.05 considered statistically significant. In this study, a total of 122 patients were included, with 53 allocated to the 3DP group and 69 to the control group. The analysis of the morphological measurements of the LA and PV taken from the workstation or direct entity measurement showed no significant difference between the two groups (P > 0.05). However, patients in the 3DP group experienced significantly shorter RFA times (97.03 ± 28.39 compared to 120.51 ± 44.76 min, t = 3.05, P = 0.003), reduced duration of radiation exposure (2.55 [interquartile range 2.01, 3.24] versus 3.20 [2.28, 3.91] min, Z = 3.23, P < 0.001), and shorter modeling times (7.68 ± 1.03 compared to 8.89 ± 1.45 min, t = 5.38, P < 0.001). 3DP technology has the potential to enhance standard RFA practices by reducing the time required for intraoperative interventions and exposure to radiation., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Swine wastewater (SW) contains high levels of traditional pollutants, antibiotics, and antibiotic resistance genes (ARGs), necessitating effective elimination. Two parallel aerobic granular sludge (AGS) reactors, R 1 and R 2 , were constructed and optimized for treating SW from two pig farms, identified as SW 1 and SW 2 . R 2 showed higher antibiotic removal efficiency, particularly in the removal of sulfonamides, while fluoroquinolones tended to adsorb onto the sludge. Process optimization by introducing an additional anoxic phase enhanced denitrification and reduced effluent ARG levels, also aiding in the improved removal of fluoroquinolones. The nitrite-oxidizing bacteria (NOB) Nitrospira accumulated after the treatment process, reaching 12.8 % in R 1 and 14.1 % in R 2 , respectively. Mantel's test revealed that pH, NH 4 + -N, and Mg significantly affected ARGs and microbial community. Sulfadiazine and sulfamethazine were found to significantly impact ARGs and the microbial communities. This study provides innovative insights into the application of AGS for the treatment of real SW., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Retinal ischemia/reperfusion (IR) injury is a common pathological process in many ophthalmic diseases. Interleukin-1β (IL-1β) is an important inflammatory factor involved in the pathology of retinal IR injury, but the mechanism by which IL-1β is regulated in such injury remains unclear. Caspase-11 non-canonical inflammasomes can regulate the synthesis and secretion of IL-1β, but its role in retinal IR injury has not been elucidated. This study aimed to evaluate the role of caspase-11 non-canonical inflammasomes in retinal IR injury., Methods: Retinal IR injury was induced in C57BL/6J mice by increasing the intraocular pressure to 110 mmHg for 60 min. The post-injury changes in retinal morphology and function and in IL-1β expression were compared between caspase-11 gene knockout (caspase-11 -/- ) mice and wild-type (WT) mice. Morphological and functional changes were evaluated using hematoxylin-eosin staining and retinal whole mount staining and using electroretinography (ERG), respectively. IL-1β expression in the retina was measured using enzyme-linked immunosorbent assay (ELISA). The levels of caspase-11-related protein were measured using western blot analysis. The location of caspase-11 in the retina was determined via immunofluorescence staining. Mouse type I astrocytes C8-D1A cells were used to validate the effects of caspase-11 simulation via hypoxia in vitro. Small-interfering RNA targeting caspase-11 was constructed. Cell viability was evaluated using the MTT assay. IL-1β expression in supernatant and cell lysate was measured using ELISA. The levels of caspase-11-related protein were measured using western blot analysis., Results: Retinal ganglion cell death and retinal edema were more ameliorated, and the ERG b-wave amplitude was better after retinal IR injury in caspase-11 -/- mice than in WT mice. Further, caspase-11 -/- mice showed lower protein expressions of IL-1β, cleaved caspase-1, and gasdermin D (GSDMD) in the retina after retinal IR injury. Caspase-11 protein was expressed in retinal glial cells, and caspase-11 knockdown played a protective role against hypoxia in C8-D1A cells. The expression levels of IL-1β, cleaved caspase-1, and GSDMD were inhibited after hypoxia in the si-caspase-11 constructed cells., Conclusions: Retinal IR injury activates caspase-11 non-canonical inflammasomes in glial cells of the retina. This results in increased protein levels of GSDMD and IL-1β and leads to damage in the inner layer of the retina., (© 2024. The Author(s).)

Background: Earlier studies have established that culturing human ovarian tissue in a 3D system with a small amount of soluble Matrigel (a basement membrane protein) for 7 days in vitro increased gene fusion and alternative splicing events, cellular functions, and potentially impacted gene expression. However, this method was not suitable for in vitro culture of human testicular tissue., Objective: To test a new method for long-time in vitro culture of testicular fragments, thawed with two different regimes, with evaluation of transcriptomic differences by RNA sequencing., Methods: Testicular tissue samples were collected, cryopreserved (frozen and thawed), and evaluated immediately after thawing and following one week of in vitro culture. Before in vitro culture, tissue fragments were encapsulated in fibrin. Four experimental groups were formed. Group 1: tissue quickly thawed (in boiling water at 100 °C) and immediately evaluated. Group 2: tissue quickly thawed (in boiling water at 100 °C) and evaluated after one week of in vitro culture. Group 3: tissue slowly thawed (by a physiological temperature 37 °C) and immediately evaluated. Group 4: tissue slowly thawed (by a physiological temperature 37 °C) and evaluated after one week of in vitro culture., Results: There are the fewest differentially expressed genes in the comparison between Group 2 and Group 4. In this comparison, significantly up-regulated genes included C4B&#95;2, LOC107987373, and GJA4, while significantly down-regulated genes included SULT1A4, FBLN2, and CCN2. Differential genes in cells of Group 2 were mainly enriched in KEGG: regulation of actin cytoskeleton, lysosome, proteoglycans in cancer, TGF-beta signaling pathway, focal adhesion, and endocytosis. These Group 2- genes were mainly enriched in GO: spermatogenesis, cilium movement, collagen fibril organization, cell differentiation, meiotic cell cycle, and flagellated spermatozoa motility., Conclusions: Encapsulation of testicular tissue in fibrin and long-time in vitro culture with constant stirring in a large volume of culture medium can reduce the impact of thawing methods on cryopreserved testicular tissue.

Background: Flavonoids are one of the most important metabolites with vast structural diversity and a plethora of potential pharmacological applications, which have drawn considerable attention in the laboratory. Nevertheless, it remains uncertain how many candidates were progressed to clinical application., Aim of Review: We carried out a critical review of natural and semi-synthetic flavonoid drugs and candidates undergoing different clinical phases worldwide by applying an adequate search method and conducted a brief cheminformatic and bioinformatic analysis. It was expected that the obtained results might narrow the screening scope and reduce the cost of drug research and development., Key Scientific Concepts of Review: To our knowledge, this is the most systematic summarization of flavonoid-based drugs and clinical candidates to date. It was found that a total of 19 flavonoid-based drugs have been approved for the market, and of these, natural flavonoids accounted for 52.6%. Besides, a total of 36 flavonoid-based clinical candidates are undergoing or suspended in different phases, and of these, natural flavonoids account for 44.4%. Thus, natural flavonoids remain the best option for finding novel agents/active templates, and when investigated in conjunction with synthetic chemicals and biologicals, they offer the potential to discover novel structures that can lead to effective agents against a variety of human diseases. Additionally, flavonoid-based marketed drugs have been successful in cardiovascular treatment, and the related drugs account for more than 30% of marketed drugs. However, the use of flavonoids as antineoplastic and immunomodulating agents is not likely for approximately 50% of the candidates suspended in the clinical stage. Interestingly, the marketed drugs covered a broader range of chemical spaces based on size, polarity, and three-dimensional structure compared to the clinical candidates. In addition, flavonoid glycosides with poor oral bioavailability account for 36.8% of the marketed drugs, and thus, they could be thoroughly investigated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Purpose: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD)., Design: Randomized, double-masked, multicenter, active-controlled, noninferiority phase II study., Participants: A total of 231 treatment-naive and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled., Methods: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa, or 2 mg aflibercept groups. Participants in all groups received 3 initial monthly loading doses, followed by treatment every 8 weeks, with assessment every 4 weeks up to week 52., Main Outcome Measures: The primary end point was the mean best-corrected visual acuity (BCVA) change from baseline to week 36. The prespecified noninferiority margin was set as -5 letters (80% confidence interval [CI])., Results: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, and +12.0 letters, respectively; least squares mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups., Conclusions: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024. Published by Elsevier Inc.)

Dry eye is a complicated ocular surface disease that causes discomfort, visual disturbance, and frequently observed ocular surface damage. Emerging hypotheses suggest probiotics may help relieve dry eye symptoms by modulating inflammation and oxidative stress. This study aimed to investigate the therapeutic effects of Streptococcus thermophilus iHA318 probiotics on dry eye using in vitro assays and an in vivo murine model of ultraviolet B (UVB) radiation-induced dry eye. In vitro analyses revealed that S. thermophilus iHA318 ® exhibited antioxidant activity and anti-inflammatory effects by inhibiting reactive oxygen species production and suppressing inflammatory cytokines. For the in vivo study, female ICR mice were assigned to normal control, UVB-induced dry eye, and UVB+iHA318 treatment groups. UVB exposure significantly decreased tear volume and tear film breakup time (TBUT) compared to normal controls. Supplementation with S. thermophilus iHA318 ® via oral gavage markedly improved tear production and TBUT on day 7 post-UVB exposure. Ocular surface photography demonstrated improved gradings of corneal opacity, smoothness, and lissamine green staining in the iHA318 group versus the UVB group. Topographical analysis further revealed improvement in the UVB-induced corneal irregularities by iHA318 treatment. Collectively, these results indicate that S. thermophilus iHA318 exerts a protective effect against dry eye symptoms by mitigating oxidative stress and inflammation, thereby preserving tear film stability and ocular surface integrity. This probiotic strain represents a promising therapeutic approach for managing dry eye syndrome.

Background: Growing cyberattacks have made it more challenging to maintain healthcare information system (HIS) security in medical institutes, especially for hospitals that provide patient portals to access patient information, such as electronic health record (EHR)., Objective: This work aims to evaluate the patient portal security risk of Taiwan's EEC (EMR Exchange Center) member hospitals and analyze the association between patient portal security, hospital location, contract category and hospital type., Methods: We first collected the basic information of EEC member hospitals, including hospital location, contract category and hospital type. Then, the patient portal security of individual hospitals was evaluated by a well-known vulnerability scanner, UPGUARD, to assess website if vulnerable to high-level attacks such as denial of service attacks or ransomware attacks. Based on their UPSCAN scores, hospitals were classified into four security ratings: absolute low risk, low to medium risk, medium to high risk and high risk. Finally, the associations between security rating, contract category and hospital type were analyzed using chi-square tests., Results: We surveyed a total of 373 EEC member hospitals. Among them, 20 hospital patient portals were rated as "absolute low risk", 104 hospital patient portals as "low to medium risk", 99 hospital patient portals as "medium to high risk" and 150 hospital patient portals as "high risk". Further investigation revealed that the patient portal security of EEC member hospitals was significantly associated with the contract category and hospital type ( P <0.001)., Conclusion: The analysis results showed that large-scale hospitals generally had higher security levels, implying that the security of low-tier and small-scale hospitals may warrant reinforcement or strengthening. We suggest that hospitals should pay attention to the security risk assessment of their patient portals to preserve patient information privacy., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Yeh et al.)

Objective: To investigate the effect of exosomes loaded with Lycium barbarum miRNA (Lb-miR2911) on spermatogenic function recovery in non-obstructive azoospermia (NOA) rats through cross-regulation of the Wnt/β-catenin signaling pathways., Methods: We established an NOA model in 30 four-week-old male SD rats by intraperitoneal injection of busulfan. At 5 weeks after modeling, we equally randomized the rats into a model control group (MC，untreated), an Lb-miR2911EXO group (Lb-miR2911EXO ，treated by intratesticular injection of Lb-miR2911-loaded exosomes), and a sham group (Shame，treated by intratesticular injection of exosomes-empty drug), with another 10 male SD rats taken as normal controls（NC）. We observed the uptake and metabolic changes of Lb-miR2911 in the testis tissue of the rats by RNA FISH at 2 and 6 weeks after treatment, detected cell proliferation, spermatogenesis and gene expressions of the Wnt/β-catenin signaling pathways in the testis tissue by Transcriptome sequencing analysis combined with Western blot and RT-PCR at 12 weeks, evaluated the recovery of the spermatogenic function based on the testis tissue morphology and sperm quality, and assessed the organ toxicity of Lb-miR2911 in the tissue and organs of the rats based on histomorphological analysis and the levels of serum TNF-α, IL-1β, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and other relevant indicators., Results: After 12 weeks of treatment, histomorphological analysis showed regular arrangement of spermatogenic cells at all levels in the testis tissue, with a large number of mature sperm in the tubular lumen, and with significantly higher Johnsen scores, testis weight, testicular index, sperm concentration and sperm motility in the Lb-miR2911EXO than in the sham group (all P< 0.05). Compared with the model controls, the Lb-miR2911EXO group exhibited remarkably down-regulated gene expression of DACT3 (P< 0.05), up-regulated expressions of DVL2 and β-catenin (P< 0.05), elevated levels of p-DVL2 and β-catenin (nucleus) proteins (P< 0.05), increased expressions of cell proliferation-related genes CCND1, CCNE1 and CCNE2 (P< 0.05) and spermatogenesis-related genes DMC1, CCR6, JAM2 and KLC3 (P< 0.05). No pathological changes were observed in the lung, liver and kidney tissues of the rats, or in the levels of serum TNF-α, IL-1β, AST, ALT, creatinine and urea nitrogen in the rats treated with Lb-miR2911EXO compared with the normal controls (P > 0.05)., Conclusion: Lb-miR2911-loaded exosomes promote spermatogenic function recovery in NOA rats through cross-regulation of the DACT3, Wnt and β-catenin signaling pathways.

Safflopentsides A-C (1-3), three highly oxidized rearranged derivatives of quinochalcone C-glycosides, were isolated from the safflower yellow pigments. Their structures were determined based on a detailed spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR), and the absolute configurations were confirmed by the comparison of experimental ECD spectra with calculated ECD spectra. Compounds 1-3 have an unprecedented cyclopentenone or cyclobutenolide ring A containing C-glucosyl group, respectively. The plausible biosynthetic pathways of compounds have been presented. At 10 μM, 2 showed strong inhibitory activity against rat cerebral cortical neurons damage induced by glutamate and oxygen sugar deprivation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The escalating prevalence of metabolic syndrome poses a significant public health challenge, particularly among aging populations, with metabolic dysfunctions contributing to pro-inflammatory states. In this review, we delved into the less recognized association between hyperuricemia (HUA), a manifestation of metabolic syndrome and a primary risk factor for gout, and age-related macular degeneration (AMD), a sight-threatening ailment predominantly affecting the elderly. In recent years, inflammation, particularly its involvement in complement pathway dysregulation, has gained prominence in AMD pathophysiology. The contradictory role of uric acid (UA) in intercellular and intracellular environments was discussed, highlighting its antioxidant properties in plasma and its pro-oxidant effects intracellularly. Emerging evidence suggests a potential link between elevated serum uric acid levels and choroid neovascularization in AMD, providing insights into the role of HUA in retinal pathologies. Various pathways, including crystal-induced and non-crystal-induced mechanisms, were proposed to indicate the need for further research into the precise molecular interactions. The implication of HUA in AMD underscores its potential involvement in retinal pathologies, which entails interdisciplinary collaboration for a comprehensive understanding of its impact on retina and related clinical manifestations., (© 2024 Federation of American Societies for Experimental Biology.)

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability in plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been underexplored. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to the leaf-infecting hemibiotrophic fungal pathogens Colletotrichum graminicola . Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 was found to suppress systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied in sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against C. graminicola in both soil conditions, but only suppressed JA production and resistance to FAW in sterile soil, while no significant impact was observed when applied in non-sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

Irinotecan plays a crucial role in the neoadjuvant chemoradiotherapy (nCRT) of rectal cancer, but its optimal dosing is still unclear. In this study, we included 101 eligible patients with the UGT1A1*28 genotype of UGT1A1*1*1 (74.3%) and UGT1A1*1*28 (25.7%) and UGT1A1*6 genotypes of GG (63.4%), GA (32.7%), and AA (3.9%). All patients received preoperative radiotherapy (50 Gy/25 fractions) with concurrent irinotecan (UGT1A1*1*1: 80 mg/m 2 ; UGT1A1*1*28: 65 mg/m 2 ) and capecitabine (CapIri). SN-38 concentrations were measured at 1.5, 24, and 49 h post-administration. Patients were divided into four groups (Q1-Q4) based on the SN-38 concentration. The complete-response (CR) rate was the primary endpoint. The analysis demonstrated that the 49 h SN-38 concentration was relatively optimal for predicting efficacy and toxicity. The Q4 group had a significantly higher CR rate than the Q1 group (p = .019), but also higher rates of adverse events (p = .009). We screened the recommended 49 h SN-38, with a 0.5-1.0 ng/mL concentration range. We also validated the correlation between UGT1A1*6 polymorphism and SN-38 concentration, along with the clinical efficacy of irinotecan. In conclusion, our study identified the relatively optimal timepoint and concentration range for monitoring SN38 concentrations and revealed the clinical significance of UGT1A1*6 and UGT1A1*28 polymorphisms in guiding irinotecan administration, offering meaningful insights for personalised irinotecan dosing., (© 2023 UICC.)

Extensive genome structure variations, such as copy number variations (CNVs) and presence/absence variations, are the basis for the remarkable genetic diversity of maize; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene ZmLOX5 leads to increased resistance of maize to herbivory by fall armyworms (FAWs). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5 , referred to as Yu796-2×LOX5 . To test whether introgression of the Yu796-2×LOX5 locus into a herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either two, one, or zero copies of the Yu796-2×LOX5 locus in the B73 background via six backcrosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2× LOX5 inbred line displayed increased resistance against FAW, associated with increased expression of ZmLOX5 , increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2× LOX5 , resulting from the increased JA catabolism. Furthermore, B73-2× LOX5 displayed reduced water loss in response to drought stress, likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into productive but susceptible crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial-mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.

Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Posterior capsule opacification (PCO) is a main complication after cataract surgery and intraocular lens (IOLs) implantation and is attributed to residual lens epithelial cells (LECs) migrating to the IOL surface and posterior capsules. IOL surface modification has been a newly-developing research filed in recent years; however, the applicability and economical acquisition of modified materials remain unsolved. In this study, we first applied a metal-polyphenolic network coating with a self-assembly technique on the IOL surface by using tannic acid (TA) combined with AlCl 3 , which are easily acquire and applying on the IOL surface to solve the IOL transmittance affair. Using wound healing and Transwell assay to verify AZD0364 inhibits cell migration ( P < 0.05), the lipopolysaccharide-induced macrophage inflammation model to verify pterostilbene (PTE) inhibits the inflammatory reaction ( P < 0.01). By optimizes its self-assembly coating parameters and calculating its drug release kinetics, we successfully loaded these two drugs on the coating, named TA (AZD0364/PTE) IOL. Its surface morphology characteristics were analyzed by scanning electron microscope, x-ray photoelectron spectrometer and water contact angle. The optical performance was carefully investigated by optical instruments and equipment ( n = 3). The in vitro results showed that TA (AZD0364/PTE) IOL can significantly inhibit cell adhesion and acute inflammation ( n = 3, P < 0.0001). Importantly, after in vivo implantation for 28 d with eight rabbits PCO models in two groups, the TA (AZD0364/PTE) IOL group maintained clear refracting media and decreased the inflammatory reaction compared with the original IOL group ( P < 0.05). This study provides a new applicable and economical strategy for preventing PCO and offers a reference for the next generation of IOLs that benefit cataract patients., (Creative Commons Attribution license.)

Six new iridoid glycosides were isolated from the ethyl acetate fraction of the whole plants of Hedyotis diffusa Willd. They were identified as E -6- O-p -methoxycinnamoyl-10- O -acetyl scandoside acid methyl ester ( 1 ), Z -6- O-p -methoxycinnamoyl-10- O -acetyl scandoside acid methyl ester ( 2 ), E -6- O -caffeoyl scandoside methyl ester ( 3 ), E -6- O - p -coumaroyl-6'- O -acetyl scandoside methyl ester ( 4 ), Z -6- O - p -coumaroyl-6'- O -acetyl scandoside methyl ester ( 5 ), and E -6- O - p -coumaroyl-4'- O -acetyl scandoside methyl ester ( 6 ). The structures of them were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, and NMR). They were screened for anti-inflammatory effect, antioxidant effect, antitumor effect, and neuroprotective effect and did not show potent activities.

Introduction: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD)., Methods: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated., Results: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups., Conclusions: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice., Trial Registration: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019)., (© 2023. The Author(s).)

Seventeen undescribed iridoid derivatives (1-17) and four known compounds (18-21) were isolated from the whole plant of Hedyotis diffusa Willd. Their structures were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, CD, and 1D and 2D NMR). It is noteworthy that compounds 1-8, which possess unique long-chain aliphatic acid moiety, were reported for the first time among the iridoid natural products. All compounds were evaluated for their anti-inflammatory activities in lipopolysaccharide-induced RAW 264.7 cells. Compounds 2, 4, and 6 showed significant suppression effects on nitric oxide production, with IC 50 values of 5.69, 6.16, and 6.84 μM, respectively. The structure-activity relationships of these compounds indicated that long-chain aliphatic moieties at C-10 might be the key group for their anti-inflammatory activities. The therapeutic properties of these iridoid derivatives could give an insight into utilizing H. diffusa as a natural source of anti-inflammatory agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cryopreservation of human testicular tissue, as a key element of anticancer therapy, includes the following stages: saturation with cryoprotectants, freezing, thawing, and removal of cryoprotectants. According to the point of view existing in "classical" cryobiology, the thawing mode is the most important consideration in the entire process of cryopreservation of any type of cells, including cells of testicular tissue. The existing postulate in cryobiology states that any frozen types of cells must be thawed as quickly as possible. The technologically maximum possible thawing temperature is 100 °C, which is used in our technology for the cryopreservation of testicular tissue. However, there are other points of view on the rate of cell thawing, according to how thawing should be carried out at physiological temperatures. In fact, there are morphological and functional differences between immature (from prepubertal patients) and mature testicular tissue. Accordingly, the question of the influence of thawing temperature on both types of tissues is relevant. The purpose of this study is to explore the transcriptomic differences of cryopreserved mature and immature testicular tissue subjected to different thawing methods by RNA sequencing. Collected and frozen testicular tissue samples were divided into four groups: quickly (in boiling water at 100 °C) thawed cryopreserved mature testicular tissue (group 1), slowly (by a physiological temperature of 37 °C) thawed mature testicular tissue (group 2), quickly thawed immature testicular tissue (group 3), and slowly thawed immature testicular tissue (group 4). Transcriptomic differences were assessed using differentially expressed genes (DEG), the Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), and protein-protein interaction (PPI) analyses. No fundamental differences in the quality of cells of mature and immature testicular tissue after cryopreservation were found. Generally, thawing of mature and immature testicular tissue was more effective at 100 °C. The greatest difference in the intensity of gene expression was observed in ribosomes of cells thawed at 100 °C in comparison with cells thawed at 37 °C. In conclusion, an elevated speed of thawing is beneficial for frozen testicular tissue., Competing Interests: The authors declare no conflict of interest.

Background: A stroke frequently results in impaired performance of activities of daily life. Many of these are highly dependent on effective coordination between the two arms. In the context of bimanual movements, cyclic rhythmical bilateral arm coordination patterns can be classified into two fundamental modes: in-phase (bilateral homologous muscles contract simultaneously) and anti-phase (bilateral muscles contract alternately) movements. We aimed to investigate how patients with left (LHS) and right (RHS) hemispheric stroke are differentially affected in both individual-limb control and inter-limb coordination during bilateral movements., Methods: We used kinematic measurements to assess bilateral coordination abilities of 18 chronic hemiparetic stroke patients (9 LHS; 9 RHS) and 18 age- and sex-matched controls. Using KINARM upper-limb exoskeleton system, we examined individual-limb control by quantifying trajectory variability in each hand and inter-limb coordination by computing the phase synchronization between hands during anti- and in-phase movements., Results: RHS patients exhibited greater impairment in individual- and inter-limb control during anti-phase movements, whilst LHS patients showed greater impairment in individual-limb control during in-phase movements alone. However, LHS patients further showed a swap in hand dominance during in-phase movements., Conclusions: The current study used individual-limb and inter-limb kinematic profiles and showed that bilateral movements are differently impaired in patients with left vs. right hemispheric strokes. Our results demonstrate that both fundamental bilateral coordination modes are differently controlled in both hemispheres using a lesion model approach. From a clinical perspective, we suggest that lesion side should be taken into account for more individually targeted bilateral coordination training strategies., Trial Registration: the current experiment is not a health care intervention study., (© 2023. The Author(s).)

Six undescribed lavandulylated flavonoids (1-6) were isolated from the roots of Sophora flavescens. Remarkably, compounds 1 and 2, which were composed of a flavane unit and a phloroglucinol unit, were the first reported dimers. Compounds 3 and 4 were the first reported neoflavonoids with lavandulyl units. Compounds 5 and 6 were chalcone with oxidized lavandulyl units. Their structures were fully characterized by cumulative analyses of UV, IR, HRESIMS, NMR and ECD spectroscopic data, along with computational calculations through density functional theory. Compounds 1 and 2 showed significant protein tyrosine phosphatase-1B inhibitory activities with IC 50 values of 2.669 and 3.596 μM, respectively., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The distribution and transport of atmospheric microplastics (AMPs) have raised concerns regarding their potential effects on the environment and human health. Although previous studies have reported the presence of AMPs at ground level, there is a lack of comprehensive understanding of their vertical distribution in urban environments. To gain insight into the vertical profile of AMPs, field observations were conducted at four different heights (ground level, 118 m, 168 m and 488 m) of the Canton Tower in Guangzhou, China. Results showed that the profiles of AMPs and other air pollutants had similar layer distribution patterns, although their concentrations differed. The majority of AMPs were composed of polyethylene terephthalate and rayon fibers ranging from 30 to 50 μm. As a result of atmospheric thermodynamics, AMPs generated at ground level were only partially transported upward, leading to a decrease in their abundance with increasing altitude. The study found that the stable atmospheric stability and lower wind speed between 118 m and 168 m resulted in the formation of a fine layer where AMPs tended to accumulate instead of being transported upward. This study for the first time delineated the vertical profile of AMPs within the atmospheric boundary layer, providing valuable data for understanding the environmental fate of AMPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The Klotho null mutation is known to lead to accelerated aging in many organs, but its effects on tear secretion and lacrimal gland (LG) senescence have not been addressed. This study investigated whether the Klotho null mutation would lead to a dry eye status and the outcome of LG without Klotho function. The Klotho ( -/- ) mutant mice showed reduced LG size and tear volume on the 8th week, as compared to their littermates ( +/+, +/- ). Hematoxylin-Eosin and Masson's trichrome staining were performed to determine morphological changes and collagen deposition. Traits of LG aging, including acinar atrophy, thickened capsules, and more collagen depositions, were observed. Immunohistochemical detections for Klotho, α-SMA, MDA, 8-OHdG, vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), MMP-2, MMP-9, and FGF-23 were performed and compared among the three genotypes ( +/+ , +/- , -/- ) at 6 and 8 weeks of age for mechanism analyses. Unexpectedly, the Klotho protein was not detected in the LG of all the three genotypes, indicating indirect effects from the Klotho null mutation. Further analyses showed abundant MDA and 8-OHdG detected in the Klotho ( -/- ) LG on the 8th week, indicating elevated oxidative stress. In addition, both sympathetic and parasympathetic neural transducing activities, as represented by TH and VIP expression, respectively, and α-SMA were increased in LGs with Klotho mutations. Furthermore, MMP-2 and MMP-9 expression were elevated, with FGF-23 expression being decreased on the 8th week in the Klotho ( -/- ) LG. In conclusion, characteristics of age-related LG degeneration were found in the Klotho null mutant mice. These traits support the use of Klotho mutant mice as a model of age-related dry eye disease.

Foliage-feeding fall armyworm (FAW; Spodoptera frugiperda ) and root-feeding western corn rootworm (WCR; Diabrotica virgifera virgifera ) are maize ( Zea mays L.) pests that cause significant yield losses. Jasmonic acid (JA) plays a pivotal defense role against insects. 12-oxo-phytodienoic acid (12-OPDA) is converted into JA by peroxisome-localized OPDA reductases (OPR). However, little is known about the physiological functions of cytoplasmic OPRs. Here, we show that disruption of ZmOPR2 reduced wound-induced JA production and defense against FAW while accumulating more JA catabolites. Overexpression of ZmOPR2 in Arabidopsis enhanced JA production and defense against beet armyworm (BAW; Spodoptera exigua ). In addition, lox10opr2 double mutants were more susceptible than either single mutant, suggesting that ZmOPR2 and ZmLOX10 uniquely and additively contributed to defense. In contrast to the defensive roles of ZmOPR2 and ZmLOX10 in leaves, single mutants did not display any alteration in root herbivory defense against WCR. Feeding on lox10opr2 double mutants resulted in increased WCR mortality associated with greater herbivory-induced production of insecticidal death acids and ketols. Thus, ZmOPR2 and ZmLOX10 cooperatively inhibit the synthesis of these metabolites during herbivory by WCR. We conclude that ZmOPR2 and ZmLOX10 regulate JA-mediated resistance in leaves against FAW while suppressing insecticidal oxylipin synthesis in roots during WCR infestation.

Objective: A small animal model would be an effective tool for research on the pathophysiology of cardiopulmonary bypass (CPB). However, numerous CPB models do not involve myocardial arrest and resuscitation. The aim of this research is to establish an easily achievable myocardial arrest and resuscitation CPB model through hyperkalemia and landiolol, simulating clinical cardiac surgery., Materials and Methods: Ten Sprague-Dawley rats were chosen for CPB. Rats underwent sevoflurane inhalation induction anesthesia and were sustained in an anesthesia state by intubation and intraperitoneal injection's of esketamine and propofol. The entire CPB circuit include a reservoir, a membrane oxygenator and a roller pump, which were connected into a complete loop via silicon tubes and infusion tube.After CPB was established through the tail artery and internal jugular vein, cardioplegic arrest was induced and maintained for 5 min at a rectum temperature of 28.5 ± 0.5°C with hyperkalemia and landiolol. Calcium chloride, epinephrine and insulin were then used for resuscitation., Result: All rats successfully finished cardioplegic arrest, resuscitation procedure and survived 2 h postoperatively. Mean hematocrit during CPB was significantly lower than physiologic values of the baseline. The mean time of arrest-resuscitation and CPB was 5.4 ± 0.8 min and 98.5 ± 5.0 min. The blood gas at each detection point were in range with the normal standard requirement of CPB., Conclusion: The establishment of cardioplegic arrest and resuscitation procedure via hyperkalemia and landiolol during CPB of WD rat could be achieved successfully. This animal model could be an alternative organ injury research on organ injury of patients undergoing cardiac surgery., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To explore the clinical and pathological characteristics of thirteen patients with orbital liposarcoma., Methods: The clinical history data of thirteen patients diagnosed as orbital liposarcoma at Beijing Tongren Hospital, from 2006 to 2021 were collected and analyzed. The data includes age, gender, affected orbital side, course of disease, status of disease (primary or recurrent), clinical manifestations, preoperative visual acuity, operative treatment, the relations between liposarcoma and surrounding tissue, longest diameter of liposarcoma, histological subtype, immunohistochemical indicators, follow-up treatment and prognosis., Results: The initial symptoms are diverse. Proptosis is the most frequent chief complaint and the others included vision loss, epiphora, diplopia, and eyelid palpable mass. Results of imaging examination [computed tomography (CT) or magnetic resonance imaging (MRI)] showed orbital mass. In terms of treatment, 10 patients received tumor resection, and the mean longest diameter of the tumor was 3.39±1.36 cm. The other 3 patients had optic nerve invaded, so they received orbital exenteration. Pathological examination results confirmed the diagnose of liposarcoma for 13 patients. Six patients displayed as myxoid type, and three patients in each type of dedifferentiated and well-differentiated type. One patient was verified as pleomorphic, which was a rare type of liposarcoma. All of the patients showed Vimentin positive, and most showed CD34 and S-100 positive. Besides, four patients showed smooth muscle actin positive. All thirteen patients were alive., Conclusion: Orbital liposarcoma is a rare disease and it has no specific clinical manifestation. The diagnosis of liposarcoma should be considered when proptosis and orbital mass occurred in orbit. It is recommended to perform pathological examination to achieve early detection and early treatment., (International Journal of Ophthalmology Press.)

13-Lipoxygenases (LOXs) initiate the synthesis of jasmonic acid (JA), the best-understood oxylipin hormone in herbivory defense. However, the roles of 9-LOX-derived oxylipins in insect resistance remain unclear. Here, we report a novel anti-herbivory mechanism mediated by a tonoplast-localized 9-LOX, ZmLOX5, and its linolenic acid-derived product, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA). Transposon-insertional disruption of ZmLOX5 resulted in the loss of resistance to insect herbivory. lox5 knockout mutants displayed greatly reduced wound-induced accumulation of multiple oxylipins and defense metabolites, including benzoxazinoids, abscisic acid (ABA), and JA-isoleucine (JA-Ile). However, exogenous JA-Ile failed to rescue insect defense in lox5 mutants, while applications of 1 μM 9,10-KODA or the JA precursor, 12-oxo-phytodienoic acid (12-OPDA), restored wild-type resistance levels. Metabolite profiling revealed that exogenous 9,10-KODA primed the plants for increased production of ABA and 12-OPDA, but not JA-Ile. While none of the 9-oxylipins were able to rescue JA-Ile induction, the lox5 mutant accumulated lower wound-induced levels of Ca 2+ , suggesting this as a potential explanation for lower wound-induced JA. Seedlings pretreated with 9,10-KODA exhibited rapid or more robust wound-induced defense gene expression. In addition, an artificial diet supplemented with 9,10-KODA arrested fall armyworm larvae growth. Finally, analysis of single and double lox5 and lox10 mutants showed that ZmLOX5 also contributed to insect defense by modulating ZmLOX10-mediated green leaf volatile signaling. Collectively, our study uncovered a previously unknown anti-herbivore defense and hormone-like signaling activity for a major 9-oxylipin α-ketol., (Copyright © 2023 The Author. Published by Elsevier Inc. All rights reserved.)

Cataracts, a prevalent age-related eye condition, pose a significant global health concern, with rising rates due to an aging population and increased digital device usage. In Taiwan, cataract prevalence is particularly high, reaching up to 90% among individuals aged 70 and above. The lens of the eye absorbs short-wave light, which can lead to oxidative stress in lens epithelial cells and contribute to cataract formation. Exposure to ultraviolet (UV) light further exacerbates the risk of cataracts by generating reactive oxygen species. Heat-shock proteins (HSPs), involved in protein maintenance and repair, have been linked to cataract development. Cordyceps cicadae ( C. cicadae ), a traditional Chinese medicine, has a long history of use and is known for its pharmacological effects. N6-(2-hydroxyethyl) adenosine (HEA), a bioactive compound found in C. cicadae , exhibits anti-inflammatory, immunomodulatory, and neuroprotective properties. Previous studies have shown that C. cicadae mycelial extracts improve dry eye disease and reduce intraocular pressure in animal models. Additionally, C. cicadae possesses antioxidant properties, which are beneficial for combating cataract formation. In this study, we aim to evaluate the preventive efficacy of C. cicadae mycelial extracts in UV-induced cataract development. By investigating the ameliorative effects of C. cicadae on eye diseases and its potential role in ocular health improvement, we hope to uncover new options for cataract prevention and provide insights into the mechanisms of action. The findings of this research could provide a novel approach for nutritional supplements targeting cataract prevention, offering potential benefits in the field of ocular health.

Cuproptosis, a new type of programmed cell death (PCD), is closely related to cellular tricarboxylic acid cycle and cellular respiration, while hypoxia can modulate PCD. However, their combined contribution to tumor subtyping remains unexplored. Here, we applied a multi-omics approach to classify TCGA&#95;COADREAD based on cuproptosis and hypoxia. The classification was validated in three colorectal cancer (CRC) cohorts and extended to a pan-cancer analysis. The results demonstrated that pan-cancers, including CRC, could be divided into three distinct subgroups (cuproptosis-hypoxia subtypes, CHSs): CHS1 had active metabolism and poor immune infiltration but low fibrosis; CHS3 had contrasting characteristics with CHS1; CHS2 was intermediate. CHS1 may respond well to cuproptosis inducers, and CHS3 may benefit from a combination of immunotherapy and anti-fibrosis/anti-hypoxia therapies. In CRC, the CHSs also showed a significant difference in prognosis and sensitivity to classic drugs. Organoid-based drug sensitivity assays validated the results of transcriptomics. Cell-based assays indicated that masitinib and simvastatin had specific effects on CHS1 and CHS3, respectively. A user-friendly website based on the classifier was developed (https://fan-app.shinyapps.io/chs&#95;classifier/) for accessibility. Overall, the classifier based on cuproptosis and hypoxia was applicable to most pan-cancers and could aid in personalized cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: Posterior capsular opacification is the most common complication after cataract surgery. Abnormal proliferation, migration, epithelial-mesenchymal transition, and extracellular matrix synthesis of residual lens epithelial cells are considered to be the main pathogenic mechanisms. Hepatocyte nuclear factor 4α has been reported to regulate epithelial-mesenchymal transition in different tumors. Our objective was to investigate the role and mechanism of hepatocyte nuclear factor 4α in posterior capsular opacification., Methods: Hepatocyte nuclear factor 4α expression was tested in posterior capsular opacification rat lens capsules and cell models. Hepatocyte nuclear factor 4α was knocked down using small hairpin RNA. Cell viability was measured by Cell Counting Kit-8 assay. Cell migration ability was evaluated by wound healing and Transwell assays. Epithelial-mesenchymal transition markers were detected by Western blotting. Transcriptome sequencing was used to screen for downstream effectors of hepatocyte nuclear factor 4α. Chromatin immunoprecipitation and a dual luciferase reporter assay were used to determine the binding of hepatocyte nuclear factor 4α to the MMP2 promoter region., Results: Hepatocyte nuclear factor 4α was downregulated in posterior capsular opacification tissue and cell models. In vitro studies showed that hepatocyte nuclear factor 4α deletion facilitated cell proliferation, migration, and epithelial-mesenchymal transition protein marker expression in lens epithelial cells. Hepatocyte nuclear factor 4α knockdown promoted epithelial-mesenchymal transition and migration of lens epithelial cells via MMP2. Mechanistically, hepatocyte nuclear factor 4α decreased MMP2 expression by binding to the MMP2 promoter region. Hepatocyte nuclear factor 4α deletion also promoted epithelial-mesenchymal transition in rat lens capsules., Conclusions: We demonstrated that hepatocyte nuclear factor 4α inhibited epithelial-mesenchymal transition of lens epithelial cells by directly binding to the MMP2 promoter region and inhibiting the expression of MMP2, thus leading to retardation of posterior capsular opacification formation and development, suggesting that hepatocyte nuclear factor 4α is a potential therapeutic target for posterior capsular opacification.

Peroxisome-localized oxo-phytodienoic acid (OPDA) reductases (OPR) are enzymes converting 12-OPDA into jasmonic acid (JA). However, the biochemical and physiological functions of the cytoplasmic non-JA producing OPRs remain largely unknown. Here, we generated Mutator-insertional mutants of the maize OPR2 gene and tested its role in resistance to pathogens with distinct lifestyles. Functional analyses showed that the opr2 mutants were more susceptible to the (hemi)biotrophic pathogens Colletotrichum graminicola and Ustilago maydis, but were more resistant to the necrotrophic fungus Cochliobolus heterostrophus. Hormone profiling revealed that increased susceptibility to C. graminicola was associated with decreased salicylic acid (SA) but increased JA levels. Mutation of the JA-producing lipoxygenase 10 (LOX10) reversed this phenotype in the opr2 mutant background, corroborating the notion that JA promotes susceptibility to this pathogen. Exogenous SA did not rescue normal resistance levels in opr2 mutants, suggesting that this SA-inducible gene is the key downstream component of the SA-mediated defences against C. graminicola. Disease assays of the single and double opr2 and lox10 mutants and the JA-deficient opr7opr8 mutants showed that OPR2 negatively regulates JA biosynthesis, and that JA is required for resistance against C. heterostrophus. Overall, this study uncovers a novel function of a non-JA producing OPR as a major negative regulator of JA biosynthesis during pathogen infection, a function that leads to its contrasting contribution to either resistance or susceptibility depending on pathogen lifestyle., (© 2023 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Klotho is known for its age-suppressing function and has been implicated in sarcopenia pathology. It has recently been proposed that the adenosine A2B receptor plays a crucial role in skeletal muscle energy expenditure. However, the association between Klotho and A2B remains elusive. In this study, Klotho knockout mice, aged 10 weeks, and wild-type mice, aged 10 and 64 weeks, were used for comparison in indicators of sarcopenia (n = 6 for each group). PCR was performed to confirm the mice genotypes. Skeletal muscle sections were analyzed using hematoxylin and eosin staining as well as immunohistochemistry staining. The skeletal muscle cross-sectional area was significantly reduced in Klotho knockout mice and wild-type mice, aged 64 weeks, when compared with wild-type mice, aged 10 weeks, with a decreased percentage of type IIa and IIb myofibers. Likely impaired regenerative capacity, as reflected by the reduction of paired box 7 (Pax7)- and myogenic differentiation protein 1 (MyoD)-positive cells, was also observed in Klotho knockout mice and aged wild-type mice. 8-Hydroxy-2-deoxyguanosine expression was enhanced with Klotho knockout and aging, indicating higher oxidative stress. Adenosine A2B signaling was impaired, with a lower expression of the A2B receptor and the cAMP-response element binding protein in Klotho knockout and aged mice. The present study provides the novel finding that sarcopenia involves adenosine signaling under the influence of Klotho knockout., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Accuracy of planned corneal stromal thickness (CST) reduction is essential to the safety of laser vision correction. This study was to compare the accuracy of the planned central CST reduction in small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). A total of 77 patients (43 for SMILE, 34 for FS-LASIK using Custom-Q algorithm) were included in this retrospective study. At postoperative 6-18 months, the central CST reduction was overestimated by 18.49 ± 6.42 μm in the SMILE group (P < 0.001) and underestimated by 2.56 ± 7.79 μm in the FS-LASIK group (P = 0.064). The planned-achieved difference (PAD) of central CST reduction was positively correlated with preoperative manifest refraction spherical equivalent (MRSE) and with planned central CST reduction in both groups. When calculated by manifest refraction (MR) without nomogram adjustment, the central CST reduction was overestimated by 11.14 ± 6.53 μm in the SMILE group and underestimated by 2.83 ± 7.39 μm in the FS-LASIK group. The PAD of central CST reduction without nomogram was significantly narrowed in SMILE and maintained in FS-LASIK, suggesting estimation using MR without nomogram adjustment may be feasible for SMILE and FS-LASIK in clinical practice., (© 2023. The Author(s).)

Six undescribed tanshinones, (+)-2-Cl-tanshindiol C (1), (-)-2-Cl-tanshindiol C (2), (+)-tanshinoic acid D (3), (-)-tanshinoic acid D (4), (-)-tanshinoic acid E (5), and (+)-tanshinoic acid E (6), were isolated from the rhizome of Salvia miltiorrhiza Bunge. Their structures were elucidated based on the spectroscopic data (UV, IR, HR-ESI-MS, and NMR). The bioactive assays of all these compounds for the antioxidant activities in cardiomyocytes upon hypoxia stimulation were evaluated. The results suggested that compounds 5 and 6 exhibited good antioxidant activities in cardiomyocytes and the cell survival rates were 46.3% and 57.9% (10 -5  mol/L), respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Current ocular surface diagnostic methods may not totally meet and implement the clinical demands for early and precise treatments. The tear ferning (TF) test has been known as a quick, simple, and inexpensive procedure. This study aimed to validate the TF test as an alternative method for early determination of photokeratitis status., Methods: The tear sample was collected from the UVB-induced photokeratitis eyes and processed for TF formation. The TF patterns were graded by both the Masmali and a Sophie-Kevin (SK) grading criteria, a new set of criteria modified from the Masmali grading, for differential diagnoses. In addition, the TF test results were correlated with three clinical ocular surface indicators, including tear volume (TV), tear film break-up time (TBUT), and cornea staining, to evaluate the diagnostic capacity., Results: Differential diagnosis between the normal and the photokeratitis status was achieved by the TF test. The SK grading reflected earlier photokeratitis status than the Masmali grading criteria. The TF results were strongly correlated with the three clinical ocular surface indicators, particularly for the TBUT and cornea staining., Conclusions: The TF test was proven to have a capacity to distinguish photokeratitis from the normal status at an early stage by using the SK grading criteria. It is therefore potentially useful for photokeratitis diagnosis in the clinical settings., Translational Relevance: The TF test may fulfill the demands of precise and early diagnosis to facilitate in time the intervention for photokeratitis.

Mechanistic studies have suggested that antioxidants have beneficial effects on age-related macular degeneration (AMD). This study aimed to investigate the association between the types and sources of dietary vitamin and carotenoid intakes and AMD risk in China. A matched case-control study of 260 AMD cases and 260 matched controls was performed. The participants were interviewed for dietary information and potential confounders, and comprehensive ophthalmic examinations were performed. Conditional logistic models were used to estimate the odds ratio (OR) and 95 % confidence interval (CI) of specific vitamins and carotenoids and their main sources. When comparing the extreme quartiles, the ORs (95 % CI) were 0·30 (0·10, 0·88) for lutein and 0·28 (0·11, 0·74) for β -cryptoxanthin. The associations for other dietary vitamin and carotenoid intakes were generally weaker and non-significant. Higher intakes of spinach and egg, which are important sources of lutein, were associated with a reduced odds of AMD. ORs (95% CIs) comparing extreme categories were 0·42 (0·20, 0·88) for spinach and 0·52 (95% CI: 0·27, 0·98) for egg. Participants who were in the highest category of both egg intake and spinach intake had a much greater reduced odds of having AMD (OR: 0·23; 95% CI: 0·08, 0·71) than those in the lowest category of egg intake and spinach intake. In conclusion, a higher intake of lutein and lutein-rich foods was associated with a significantly decreased odds of AMD. These findings provide further evidence of the benefits of lutein and lutein-rich foods in the prevention of AMD.

An experiment was performed to calibrate the capability of a tactile sensor, which is based on gallium nitride (GaN) nanopillars, to measure the absolute magnitude and direction of an applied shear force without the need for any post-processing of data. The force's magnitude was deduced from monitoring the nanopillars' light emission intensity. Calibration of the tactile sensor used a commercial force/torque (F/T) sensor. Numerical simulations were carried out to translate the F/T sensor's reading to the shear force applied to each nanopillar's tip. The results confirmed the direct measurement of shear stress from 3.71 to 50 kPa, which is in the range of interest for completing robotic tasks such as grasping, pose estimation, and item discovery.

Sometimes, for medical reasons, when a frozen tissue has already thawed, an operation by re-transplantation may be cancelled, and ovarian tissues should be re-frozen for transplantation next time. Research about the repeated cryopreservation of ovarian cells is rarely reported. It has been published that there is no difference in the follicle densities, proportions of proliferation of early preantral follicles, appearance of atretic follicles, or ultrastructural quality of frozen-thawed and re-frozen-rethawed tissue. However, the molecular mechanisms of a repeated cryopreservation effect on the developmental potential of ovarian cells are unknown. The aim of our experiments was to investigate the effect of re-freezing and re-thawing ovarian tissue on gene expression, gene function annotation, and protein-protein interactions. The morphological and biological activity of primordial, primary, and secondary follicles, aimed at using these follicles for the formation of artificial ovaries, was also detected. Second-generation mRNA sequencing technology with a high throughput and accuracy was adopted to determine the different transcriptome profiles in the cells of four groups: one-time cryopreserved (frozen and thawed) cells (Group 1), two-time cryopreserved (re-frozen and re-thawed after first cryopreservation) cells (Group 2), one-time cryopreserved (frozen and thawed) and in vitro cultured cells (Group 3), and two times cryopreserved (re-frozen and re-thawed after first cryopreservation) and in vitro cultured cells (Group 4). Some minor changes in the primordial, primary, and secondary follicles in terms of the morphology and biological activity were detected, and finally, the availability of these follicles for the formation of artificial ovaries was explored. It was established that during cryopreservation, the CEBPB/CYP19A1 pathway may be involved in regulating estrogen activity and CD44 is crucial for the development of ovarian cells. An analysis of gene expression in cryopreserved ovarian cells indicates that two-time (repeated) cryopreservation does not significantly affect the developmental potential of these cells. For medical reasons, when ovarian tissue is thawed but cannot be transplanted, it can be immediately re-frozen again.