The p38/MAPK pathway as a therapeutic target to prevent therapeutic escape of breast cancer stem cells.

Cancer stem cells (CSCs) play an important role in metastasis development, tumor recurrence, and treatment resistance, and are essential for the eradication of cancer. Currently, therapies fail to eradicate CSCs due to their therapeutic stress-induced cellular escape, which leads to enhanced aggressive behaviors compared with CSCs that have never been treated. However, the underlying mechanisms regulating the therapeutic escape remain unknown. To this end, we established a model to isolate the therapeutic escaped CSCs (TSCSCs) from breast CSCs and performed the transcription profile to reveal the mechanism. Mechanistically, we demonstrated that the behavior of therapeutic escape was regulated through the p38/MAPK signaling pathway, resulting in TSCSCs exhibiting enhanced motility and metastasis. Notably, blocking the p38/MAPK signaling pathway effectively reduced motility and metastasis ability both in vitro and in vivo, which were further supported by downregulated motility-related genes and epithelial-mesenchymal transition (EMT)-related proteins vimentin and N-cadherin. The obtained findings reveal the p38/MAPK pathway as a potential therapeutic target for TSCSCs and would provide profound implications for cancer therapy.

Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38.

Background: CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs). Methods: Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 "mAb-trap" platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems. Results: Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a "mAb-trap" platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605-26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605-12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605-12C10 efficiently eradicated all established tumors in all mice. Conclusion: A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.

Association of Hyperoxia During Cardiopulmonary Bypass and Postoperative Delirium in the Pediatric Cardiac ICU.

OBJECTIVE: ICU delirium commonly complicates critical illness associated with factors such as cardiopulmonary bypass (CPB) time and the requirement of mechanical ventilation (MV). Recent reports associate hyperoxia with poorer outcomes in critically ill children. This study sought to determine whether hyperoxia on CPB in pediatric patients was associated with a higher prevalence of postoperative delirium. DESIGN: Secondary analysis of data obtained from a prospective cohort study. SETTING: Twenty-two-bed pediatric cardiac ICU in a tertiary children's hospital. PATIENTS: All patients (18 yr old or older) admitted post-CPB, with documented delirium assessment scores using the Preschool/Pediatric Confusion Assessment Method for the ICU and who were enrolled in the Precision Medicine in Pediatric Cardiology Cohort from February 2021 to November 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 148 patients, who underwent cardiac surgery, 35 had delirium within the first 72 hours (24%). There was no association between hyperoxia on CPB and postoperative delirium for all definitions of hyperoxia, including hyperoxic area under the curve above 5 predetermined Pao2 levels: 150 mm Hg (odds ratio [95% CI]: 1.176 [0.605-2.286], p = 0.633); 175 mm Hg (OR 1.177 [95% CI, 0.668-2.075], p = 0.572); 200 mm Hg (OR 1.235 [95% CI, 0.752-2.026], p = 0.405); 250 mm Hg (OR 1.204 [95% CI, 0.859-1.688], p = 0.281), 300 mm Hg (OR 1.178 [95% CI, 0.918-1.511], p = 0.199). In an additional exploratory analysis, comparing patients with delirium within 72 hours versus those without, only the z score for weight differed (mean [sd]: 0.09 [1.41] vs. -0.48 [1.82], p < 0.05). When comparing patients who developed delirium at any point during their ICU stay (n = 45, 30%), MV days, severity of illness (Pediatric Index of Mortality 3 Score) score, CPB time, and z score for weight were associated with delirium (p < 0.05). CONCLUSIONS: Postoperative delirium (72 hr from CPB) occurred in 24% of pediatric patients. Hyperoxia, defined in multiple ways, was not associated with delirium. On exploratory analysis, nutritional status (z score for weight) may be a significant factor in delirium risk. Further delineation of risk factors for postoperative delirium versus ICU delirium warrants additional study.

Compositions and sources of fluorescent water-soluble and water-insoluble organic aerosols.

Brown carbon (BrC), the light-absorbing component of organic aerosols, plays a significant role in climate change and atmospheric photochemistry. However, the water-insoluble fractions of BrC have not been extensively studied, limiting the assessment of the overall climate effects of BrC. In this study, water-soluble and -insoluble organic carbon (i.e., WSOC and WIOC) in wintertime aerosols in Hefei were subsequently fractionated, and their fluorescence properties were comparatively investigated with the excitation-emission matrix method. WIOC contributing 57.1 % was the major component of organic carbon. WSOC with the largest contribution from humic-like regions exhibited a redshift compared to WIOC. Three humic-like substances (HULIS) with different oxidation degrees and one protein-like substances (PRLIS) were identified as the major fluorescent components by the parallel factor analysis. WSOC had more highly oxygenated HULIS, whereas low-oxygenated HULIS dominated WIOC. Nighttime WIOC contained more less-oxygenated species. The positive matrix factorization analysis suggested that biomass burning (43 %) was the largest source of both fluorescent WSOC and WIOC. Coal combustion contributed much more to fluorescent WIOC (40 %), whereas secondary formation contributed more to fluorescent WSOC (12 %). During aerosol pollution episodes, the increase in fluorescence efficiency was much greater for WIOC (25 %) than for WSOC (12 %), and WSOC and WIOC experienced a redshift and blueshift in emission wavelength, respectively. WSOC had more highly oxygenated HULIS, while WIOC had more less-oxygenated HULIS in aerosol episodes than the non-episodic periods. In addition, aerosol pollution was accompanied by the increased contributions of biomass burning and coal combustion to both fluorescent WSOC and WIOC, while the decreased relative contribution of secondary formation to fluorescent WSOC. Our findings highlighted the different fluorescence properties, compositions and sources of fluorescent WSOC and WIOC, providing a comprehensive view of BrC aerosols.

Antiplatelet drug ticagrelor suppresses triple negative breast cancer metastasis by targeting PI3K.

Metastatic recurrence is still a major challenge in breast cancer treatment. Patients with triple negative breast cancer (TNBC) develop early recurrence and relapse more frequently. Due to the lack of specific therapeutic targets, new targeted therapies for TNBC are urgently needed. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is one of the active pathways involved in chemoresistance and survival of TNBC, being considered as a potential target for TNBC treatment. Our present study identified ticagrelor, an anti-platelet drug, as a pan-PI3K inhibitor with potent inhibitory activity against four isoforms of class I PI3K. At doses normally used in clinic, ticagrelor showed weak cytotoxicity against a panel of breast cancer cells, but significantly inhibited the migration, invasion and the actin cytoskeleton organization of human TNBC MDA-MB-231 and SUM-159PT cells. Mechanistically, ticagrelor effectively inhibited PI3K downstream mTOR complex 1 (mTORC1) and mTORC2 signaling by targeting PI3K and decreased the protein expression of epithelial-mesenchymal transition (EMT) markers. In vivo, ticagrelor significantly suppressed tumor cells lung metastasis in 4T1 tumor bearing BALB/c mice model and experimental lung metastasis model which was established by tail vein injection of GFP-labeled MDA-MB-231 cells. The above data demonstrated that ticagrelor can inhibit the migration and invasion of TNBC both in vitro and in vivo by targeting PI3K, suggesting that ticagrelor, a pan-PI3K inhibitor, might represent a promising therapeutic agent for the treatment of metastatic TNBC.

An electrochemical H2S sensor based on the screen printing Fe@Pt/C/PTFE sensing electrode.

A novel electrochemical gas sensor for sensitive detection of H2S at room temperature is constructed based on the Fe@Pt/C composite material. The core-shell structured Fe@Pt catalyst was synthesized by a two-step reduction method and physically dispersed in Vulcan XC-72 carbon powders. The core-shell structure increases the effective catalytic surface area of Pt while significantly reducing the usage of the noble metal Pt, leading to improved catalytic performance and decreased production costs. Additionally, the mature screen-printing process is used to coat the catalyst film. A waterproof and breathable PTFE film was used as the substrate and the parameters in the screen printing process were also optimized to achieve the best gas sensing performance of the electrode film. Through the detection of hydrogen sulfide (H2S) with different concentrations, it is found that the sensor strictly shows linear correlation in the range of 1-20 ppm, R2 = 0.99974. Notably, the sensor exhibits high sensitivity (658.45 nA ppm-1) and a low detection limit of 0.33 ppm. Moreover, the consistency and stability of the sensor are satisfactory. The constructed gas sensor is expected to be well applied to industrial H2S detection.

The joint effects of local, climatic, and spatial variables determine soil oribatid mite community assembly along a temperate forest elevational gradient.

Numerous factors influence mountain biodiversity variation across elevational gradients and recognizing the relative importance is vital for understanding species distribution mechanisms. We examined oribatid mites at nine elevations (from 600 to 2200 m a.s.l) and four vegetation types from mixed coniferous and broad-leaved forests to alpine tundra on Changbai Mountain. We assessed the contribution of environmental factors (climatic and local factors) and spatial processes (geographic or elevation distances) to oribatid mite community assembly and identified 59 oribatid mite species from 38 families and 51 genera. With increasing elevation, species richness and the Shannon index declined significantly, whereas abundance followed a hump-shaped trend. Soil TP, NH4 +-N, MAT, MAP, and elevation were the critical variables shaping oribatid mite communities based on random forest analysis. Moreover, environmental and spatial factors, and oribatid mite communities were significantly correlated based on Mantel and partial Mantel tests. Local characteristics (3.9%), climatic factors (1.9%), and spatial filtering (8.8%) played crucial roles in determining oribatid mite communities across nine elevational bands (based on variation partitioning analyses of abundance data). Within the same vegetation types, spatial processes had relatively little effects, with local characteristics the dominant drivers of oribatid mite community variation. Environmental and spatial filters together shape oribatid mite community assembly and their relative roles varied with elevation and vegetation type. These findings are crucial for the conservation, restoration, and management of Changbai mountain ecosystems in the context of climate change, along with the prediction of future vertical biotic gradient pattern evolution.

Bacillus subtilis Feed Supplementation Combined with Oral E. coli Immunization in Sows as a Tool to Reduce Neonatal Diarrhea in Piglets.

To investigate the effects of B. subtilis on the specific immune response of lactating sows to E. coli and the diarrhea rate in suckling piglets, thirty large white sows with similar farrowing dates were randomly divided into two groups: a feedback feeding (i.e., feeding a homogenate of intestinal contents and tissues from E. coli-infected piglets to sows; FB) group and a feedback feeding with B. subtilis (FB + BS) group. Serum, colostrum, and intestinal tissues from sows and piglets were collected to assess the immune response and intestinal barrier function at weaning. T and B cells from Peyer's patches (PPs) and mesenteric lymph nodes (MLNs) in lactating mice (with treatments consistent with the sows') were isolated to explore the underlying mechanism. The results showed that, compared with the FB group, the reproductive performance of sows and the growth performance of their offspring were effectively improved in the FB + BS group. Moreover, the levels of IgG/IgA and those of IgG/IgA against E. coli in the serum and colostrum of sows in the FB+BS group were increased (p < 0.05). Meanwhile, the ratio of CD4+/CD8+, CD4+CXCR5+PD1+, and B220+IgA+ cells in MLNs and PPs, and the IgA levels in the mammary glands of mice, were also increased in the FB + BS group (p < 0.05). Notably, in suckling piglets in the FB + BS group, the diarrhea rate was decreased (p < 0.05), and the intestinal barrier function and intestinal flora composition at weaning were significantly improved. Overall, these results indicated that B. subtilis feed supplementation combined with feedback feeding in pregnant and lactating sows can reduce diarrhea in suckling piglets by enhancing the maternal immune response against E. coli and intestinal barrier function in their offspring, improving survival rates and pre-weaning growth.

Natural soil biotin application activates soil beneficial microorganisms to improve the thermotolerance of Chinese cabbage.

Chinese cabbage (Brassica campestris L. syn. B. rapa), a widely cultivated leafy vegetable, faces significant challenges in annual production due to high-temperature stress, which adversely affects plant weight and quality. The need for an effective solution to mitigate these impacts is imperative for sustainable horticulture. This study explored the effects of a novel biofertilizer, natural soil biotin (NSB), on Chinese cabbage under high-temperature conditions. NSB, rich in organic matter-degrading enzymes, was applied to assess its impact on crop yield, growth, nutrient use efficiency, product quality, and safety. The study also examined the soil microbial community response to NSB application, particularly the changes in the rhizosphere soil's fungal population. The application of NSB led to an increase in the abundance of Oleomycetes, which was associated with a decrease in the diversity and abundance of harmful fungi in the rhizosphere soil. This microbial shift promoted the growth of Chinese cabbage, enhancing both plant weight and quality by fostering a more favorable growth environment. Furthermore, NSB was found to reduce lipid peroxidation in Chinese cabbage leaves under high-temperature stress (40°C/30°C, 16 h/8 h, 24 h) by boosting antioxidant enzyme activity and osmoregulatory substance content. The findings suggest that the NSB application offers a promising approach to environmentally friendly cultivation of Chinese cabbage during high-temperature seasons. It contributes to improving the crop's adaptation to climate change and soil degradation, supporting the development of sustainable agricultural practices. The integration of NSB into agricultural practices presents a viable strategy for enhancing the resilience of Chinese cabbage to high-temperature stress, thereby potentially increasing yield and improving the quality of the produce, which is crucial for the advancement of sustainable horticulture.

Oxygen-to-ammonium-nitrogen ratio as an indicator for oxygen supply management in microoxic bioanodic ammonium oxidation.

Microbial electrolysis cells (MECs) have been proven effective for oxidizing ammonium (NH4+), where the anode acts as an electron acceptor, reducing the energy input by substituting oxygen (O2). However, O2 has been proved to be essential for achieving high removal rates MECs. Thus, precise control of oxygen supply is crucial for optimizing treatment performance and minimizing energy consumption. Unlike previous studies focusing on dissolved oxygen (DO) levels, this study introduces the O2/NH4+-N ratio as a novel control parameter for balancing oxidation rates and the selectivity of NH4+ oxidation towards dinitrogen gas (N2) under limited oxygen condition. Our results demonstrated that the O2/NH4+-N ratio is a more relevant oxygen supply indicator compared to DO level. Oxygen served as a more favorable electron acceptor than the electrode, increasing NH4+ oxidation rates but also resulting in more oxidized products such as nitrate (NO3-). Additionally, nitrous oxide (N2O) and N2 production were higher with the electrode as the electron acceptor compared to oxygen alone. An O2/NH4+-N ratio of 0.5 was found to be optimal, achieving a balance between product selectivity for N2 (51.4 % ± 4.5 %) and oxidation rates (344.6 ± 14.7 mg-N/L*d), with the columbic efficiency of 30.7 % ± 2.0 %. Microbial community analysis revealed that nitrifiers and denitrifiers were the primary bacteria involved, with oxygen promoting the growth of nitrite-oxidizing bacteria, thus facilitating complete NH4+ oxidation to NO3-. Our study provides new insights and guidelines on the appropriate oxygen dosage, offering strategies into optimizing operational conditions for NH4+ removal using MECs.

Biological functions and potential mechanisms of miR­143­3p in cancers (Review).

In recent years, microRNAs (miRNAs or miRs) have been increasingly studied for their role in cancer and have shown potential as cancer biomarkers. miR­143­3p and miR­143­5p are the mature miRNAs derived from pre­miRNA­143. At present, there are numerous studies on the function of miR­143­3p in cancer progression, but there are no systematic reviews describing the function of miR­143­3p in cancer. It is widely considered that miR­143­3p is downregulated in most malignant tumors and that upstream regulators can act on this gene, which in turn regulates the corresponding target to act on the tumor. In addition, miRNA­143­3p can regulate target genes to affect the biological process of tumors through various signaling pathways, such as the PI3K/Akt, Wnt/ß­catenin, AKT/STAT3 and Ras­Raf­MEK­ERK pathways. The present review comprehensively described the biogenesis of miR­143­3p, the biological functions of miR­143­3p and the related roles and mechanisms in different cancer types. The potential of miR­143­3p as a biomarker for cancer was also highlighted and valuable future research directions were discussed.

Rapid production of COVID-19 subunit vaccine candidates and their immunogenicity evaluation in pigs.

The emergence of various variants of concern (VOCs) necessitates the development of more efficient vaccines for COVID-19. In this study, we established a rapid and robust production platform for a novel subunit vaccine candidate based on eukaryotic HEK-293 T cells. The immunogenicity of the vaccine candidate was evaluated in pigs. The results demonstrated that the pseudovirus neutralizing antibody (pNAb) titers reached 7751 and 306 for the SARS-CoV-2 Delta and Omicron variants, respectively, after the first boost. Subsequently, pNAb titers further increased to 10,201 and 1350, respectively, after the second boost. Additionally, ELISPOT analysis revealed a robust T-cell response characterized by IFN-γ (171 SFCs/106 cells) and IL-2 (101 SFCs/106 cells) production. Our study demonstrates that a vaccine candidate based on the Delta variant spike protein may provide strong and broad protection against the prototype SARS-CoV-2 and VOCs. Moreover, the strategy for the efficient and stable expression of recombinant proteins utilizing HEK-293 T cells can be employed as a universal platform for future vaccine development.

Microglia in radiation-induced brain injury: Cellular and molecular mechanisms and therapeutic potential.

BACKGROUND: Radiation-induced brain injury is a neurological condition resulting from radiotherapy for malignant tumors, with its underlying pathogenesis still not fully understood. Current hypotheses suggest that immune cells, particularly the excessive activation of microglia in the central nervous system and the migration of peripheral immune cells into the brain, play a critical role in initiating and progressing the injury. This review aimed to summarize the latest advances in the cellular and molecular mechanisms and the therapeutic potential of microglia in radiation-induced brain injury. METHODS: This article critically examines recent developments in understanding the role of microglia activation in radiation-induced brain injury. It elucidates associated mechanisms and explores novel research pathways and therapeutic options for managing this condition. RESULTS: Post-irradiation, activated microglia release numerous inflammatory factors, exacerbating neuroinflammation and facilitating the onset and progression of radiation-induced damage. Therefore, controlling microglial activation and suppressing the secretion of related inflammatory factors is crucial for preventing radiation-induced brain injury. While microglial activation is a primary factor in neuroinflammation, the precise mechanisms by which radiation prompts this activation remain elusive. Multiple signaling pathways likely contribute to microglial activation and the progression of radiation-induced brain injury. CONCLUSIONS: The intricate microenvironment and molecular mechanisms associated with radiation-induced brain injury underscore the crucial roles of immune cells in its onset and progression. By investigating the interplay among microglia, neurons, astrocytes, and peripheral immune cells, potential strategies emerge to mitigate microglial activation, reduce the release of inflammatory agents, and impede the entry of peripheral immune cells into the brain.

Characterize direct protein interactions with enrichable, cleavable and latent bioreactive unnatural amino acids.

Latent bioreactive unnatural amino acids (Uaas) have been widely used in the development of covalent drugs and identification of protein interactors, such as proteins, DNA, RNA and carbohydrates. However, it is challenging to perform high-throughput identification of Uaa cross-linking products due to the complexities of protein samples and the data analysis processes. Enrichable Uaas can effectively reduce the complexities of protein samples and simplify data analysis, but few cross-linked peptides were identified from mammalian cell samples with these Uaas. Here we develop an enrichable and multiple amino acids reactive Uaa, eFSY, and demonstrate that eFSY is MS cleavable when eFSY-Lys and eFSY-His are the cross-linking products. An identification software, AixUaa is developed to decipher eFSY mass cleavable data. We systematically identify direct interactomes of Thioredoxin 1 (Trx1) and Selenoprotein M (SELM) with eFSY and AixUaa.

Cardiovascular disease: Mitochondrial dynamics and mitophagy crosstalk mechanisms with novel programmed cell death and macrophage polarisation.

Several cardiovascular illnesses are associated with aberrant activation of cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis, and macrophage polarisation as hallmarks contributing to vascular damage and abnormal cardiac function. Meanwhile, these three novel forms of cellular dysfunction are closely related to mitochondrial homeostasis. Mitochondria are the main organelles that supply energy and maintain cellular homeostasis. Mitochondrial stability is maintained through a series of regulatory pathways, such as mitochondrial fission, mitochondrial fusion and mitophagy. Studies have shown that mitochondrial dysfunction (e.g., impaired mitochondrial dynamics and mitophagy) promotes ROS production, leading to oxidative stress, which induces cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage M1 phenotypic polarisation. Therefore, an in-depth knowledge of the dynamic regulation of mitochondria during cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage polarisation is necessary to understand cardiovascular disease development. This paper systematically summarises the impact of changes in mitochondrial dynamics and mitophagy on regulating novel cellular dysfunctions and macrophage polarisation to promote an in-depth understanding of the pathogenesis of cardiovascular diseases and provide corresponding theoretical references for treating cardiovascular diseases.

A flexible, stretchable and wearable strain sensor based on physical eutectogels for deep learning-assisted motion identification.

Physical eutectogels as a newly emerging type of conductive gel have gained extensive interest for the next generation multifunctional electronic devices. Nevertheless, some obstacles, including weak mechanical performance, low self-adhesive strength, lack of self-healing capacity, and low conductivity, hinder their practical use in wearable strain sensors. Herein, lignin as a green filler and a multifunctional hydrogen bond donor was directly dissolved in a deep eutectic solvent (DES) composed of acrylic acid (AA) and choline chloride, and lignin-reinforced physical eutectogels (DESL) were obtained by the polymerization of AA. Due to the unique features of lignin and DES, the prepared DESL eutectogels exhibit good transparency, UV shielding capacity, excellent mechanical performance, outstanding self-adhesiveness, superior self-healing properties, and high conductivity. Based on the aforementioned integrated functions, a wearable strain sensor displaying a wide working range (0-1500%), high sensitivity (GF = 18.15), rapid responsiveness, and excellent stability and durability (1000 cycles) and capable of detecting diverse human motions was fabricated. Additionally, by combining DESL sensors with a deep learning technique, a gesture recognition system with accuracy as high as 98.8% was achieved. Overall, this work provides an innovative idea for constructing multifunction-integrated physical eutectogels for application in wearable electronics.

Randomized trial comparing the effects of a 3D head-up system and microscope eyepiece-assisted simulated vitrectomy with intraocular illumination on the ocular surface of an operator.

BACKGROUND: To compare the effects of a 3D head-up system and microscope eyepiece-assisted simulated vitrectomy intraocular illumination on the ocular surface of an operator. METHODS: This was a prospective randomized controlled study. According to the application system, thirty ophthalmic operators (60 eyes) were randomly divided into 3D and eyepiece groups. Under different intensities of intraocular illumination, operators in both groups viewed the fundus model through a 3D display screen or microscopic eyepiece for 2 h. Objective examinations and a subjective symptom questionnaire were used immediately after the test to evaluate the ocular surface of the operators. Objective examinations included nonintrusion tear meniscus height (NIKTMH), nonintrusion break-up time (NIKBUT), and bulbar redness and strip meniscometry tube (SMTube) measurements. Statistical analyses were performed by using SPSS 26.0 software. RESULTS: After the test, the NIKTMH, NIKBUT and SMTube measurements decreased; however, the degree of change varied among the groups of different systems. The differences between the 3D group and the eyepiece group in NIKTMH measurements, SMTube measurements, subjective symptom scores (eye dryness, difficulty focusing, and cervical pain), and light intensity reaching the ocular surface of the operators were statistically significant (P < 0.05). All of the objective and subjective tests showed that the 3D group had fewer effects on the NIKTMH and SMTube measurements, and the subjective comfort of the 3D group was greater. CONCLUSION: For both 3D screens and eyepieces, simulated vitrectomy with intraocular illumination for two hours can lead to discomfort and abnormalities in the operator's ocular surface; however, these abnormalities are less severe in the 3D group. TRIAL REGISTRATION: This trial was registered on December 22, 2022, at the Chinese Clinical Trials Registry with NO. ChiCTR2200066989.

Associations of life's essential 8 with extent of multi-territorial atherosclerotic plaques and stenosis: a cross-sectional study.

BACKGROUND: Life's Essential 8 (LE8), the recently updated construct for quantifying cardiovascular health, is related to the risks of cardiovascular events. The present study aimed to evaluate associations of LE8 score with the multi-territorial extent of atherosclerosis in a community-dwelling population. METHODS: Data were derived from the baseline cross-sectional survey of the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in Lishui City. The LE8 included overall, medical and behavior LE8 scores, and were categorized as low (< 60), moderate (60-<80), and high (≥ 80) groups. Vascular magnetic resonance imaging was used to evaluate intracranial and extracranial arteries; thoracoabdominal computed tomography angiography to evaluate coronary, subclavian, aorta, renal, ilio-femoral arteries; and ankle-brachial index to evaluate peripheral arteries. The presence of atherosclerotic plaque or stenosis in any territory was defined as plaque or vascular stenosis with 1 territory affected or more in these arteries. The extent of atherosclerotic plaques or stenosis was assessed according to the number of these 8 vascular sites affected, and graded as four grades (none, single territory, 2-3 territories, 4-8 territories). RESULTS: Of 3065 included participants, the average age was 61.2 ± 6.7 years, and 53.5% were women (n = 1639). The moderate and high overall LE8 groups were associated with lower extent of multi-territorial plaques [common odds ratio (cOR) 0.44, 95% confidence interval (CI), 0.35-0.55; cOR 0.16, 95%CI, 0.12-0.21; respectively] and stenosis (cOR 0.51, 95%CI, 0.42-0.62; cOR 0.16, 95%CI, 0.12-0.21; respectively) after adjustment for potential covariates. Similar results were observed for medical LE8 score with the extent of multi-territorial plaques and stenosis (P < 0.05). We also found the association between behavior LE8 score and the extent of multi-territorial stenosis (P < 0.05). CONCLUSIONS: The higher LE8 scores, indicating healthier lifestyle, were associated with lower presence and extent of atherosclerotic plaque and stenosis in southern Chinese adults. Prospective studies are needed to further validate these findings.

Phosphine-Catalyzed γ'-Carbon 1,6-Conjugate Addition of α-Succinimide Substituted Allenoates with Para-Quinone Methides: Synthesis of 4-Diarylmethylated 3,4-Disubstituted Maleimides.

In this paper, an interesting γ'-carbon 1,6-conjugate addition for phosphine-catalyzed α-succinimide substituted allenoates has been disclosed. A wide array of substrates was found to participate in the reaction, resulting in the production of diverse 4-diarylmethylated 3,4-disubstituted maleimides with satisfactory to outstanding yields. Furthermore, a plausible mechanism for the reaction was proposed by the investigators.

Comparative time-dependent proteomics reveal the tolerance of cancer cells to magnetic iron oxide nanoparticles.

Cancer is one of the most challenging diseases in the world. Recently, iron oxide nanoparticles (IONPs) are emerging materials with rapid development and high application value, and have shown great potential on tumor therapy due to their unique magnetic and biocompatible properties. However, some data hint us that IONPs were toxic to normal cells and vital organs. Thus, more data on biosafety evaluation is urgently needed. In this study, we compared the effects of silicon-coated IONPs (Si-IONPs) on two cell types: the tumor cells (Hela) and the normal cells (HEK293T, as 293 T for short), compared differences of protein composition, allocation and physical characteristics between these two cells. The major findings of our study pointed out that 293 T cells death occurred more significant than that of Hela cells after Si-IONPs treatment, and the rate and content of endocytosis of Si-IONPs in 293 T cells was more prominent than in Hela cells. Our results also showed Si-IONPs significant promoted the production of reactive oxygen species and disturbed pathways related to oxidative stress, iron homeostasis, apoptosis and ferroptosis in both two types of cells, however, Hela cells recovered from these disturbances more easily than 293 T. In conclusion, compared with Hela cells, IONPs are more likely to induce 293 T cells death and Hela cells have their own unique mechanisms to defense invaders, reminding scientists that future in vivo and in vitro studies of nanoparticles need to be cautious, and more safety data are needed for further clinical treatment.