An update of the molecular mechanisms underlying anthracycline induced cardiotoxicity.

Anthracycline drugs mainly include doxorubicin, epirubicin, pirarubicin, and aclamycin, which are widely used to treat a variety of malignant tumors, such as breast cancer, gastrointestinal tumors, lymphoma, etc. With the accumulation of anthracycline drugs in the body, they can induce serious heart damage, limiting their clinical application. The mechanism by which anthracycline drugs cause cardiotoxicity is not yet clear. This review provides an overview of the different types of cardiac damage induced by anthracycline-class drugs and delves into the molecular mechanisms behind these injuries. Cardiac damage primarily involves alterations in myocardial cell function and pathological cell death, encompassing mitochondrial dysfunction, topoisomerase inhibition, disruptions in iron ion metabolism, myofibril degradation, and oxidative stress. Mechanisms of uptake and transport in anthracycline-induced cardiotoxicity are emphasized, as well as the role and breakthroughs of iPSC in cardiotoxicity studies. Selected novel cardioprotective therapies and mechanisms are updated. Mechanisms and protective strategies associated with anthracycline cardiotoxicity in animal experiments are examined, and the definition of drug damage in humans and animal models is discussed. Understanding these molecular mechanisms is of paramount importance in mitigating anthracycline-induced cardiac toxicity and guiding the development of safer approaches in cancer treatment.

A Ligand-Directed Spatial Regulation to Structural and Functional Tunability in Aggregation-Induced Emission Luminogen-Functionalized Organic-Inorganic Nanoassemblies.

Aggregation-induced emission luminogen (AIEgen)-functionalized organic-inorganic hybrid nanoparticles (OINPs) are an emerging category of multifunctional nanomaterials with vast potential applications. The spatial arrangement and positioning of AIEgens and inorganic compounds in AIEgen-functionalized OINPs determine the structures, properties, and functionalities of the self-assembled nanomaterials. In this work, a facile and general emulsion self-assembly tactic for synthesizing well-defined AIEgen-functionalized OINPs is proposed by coassembling alkane chain-functionalized inorganic nanoparticles with hydrophobic organic AIEgens. As a proof of concept, the self-assembly and structural evolution of plasmonic-fluorescent hybrid nanoparticles (PFNPs) from concentric circle to core shell and then to Janus structures is demonstrated by using alkane chain-modified AuNPs and AIEgens as building blocks. The spatial position of AuNPs in the signal nanocomposite is controlled by varying the alkane ligand length and density on the AuNP surface. The mechanism behind the formation of various PFNP nanostructures is also elucidated through experiments and theoretical simulation. The obtained PFNPs with diverse structures exhibit spatially tunable optical and photothermal properties for advanced applications in multicolor and multimode immunolabeling and photothermal sterilization. This work presents an innovative synthetic approach of constructing AIEgen-functionalized OINPs with diverse structures, compositions, and functionalities, thereby championing the progressive development of these OINPs.

Surface Engineering and Programmed Self-Assembly of Silica Nanoparticles with Controllable Polystyrene/Poly(4-vinybenzyl azide) Patches.

The programmed self-assembly of patchy nanoparticles (NPs) through a bottom-up approach is an efficient strategy for producing highly organized materials with a predetermined architecture. Herein, we report the preparation of di- and trivalent silica NPs with polystyrene (PS)/poly(4-vinylbenzyl azide) (PVBA) patches and assemble them in a THF mixture by lowering the solvent quality. Silica-PS/PVBA colloidal hybrid clusters were synthesized through the seeded growth emulsion copolymerization of styrene and 4-vinylbenzyl azide (VBA) in varying ratios. Subsequently, macromolecules on silica NPs originating from the copolymerization of growing PS or PVBA chains with the surface-grafted MMS compatibilizer are engineered by fine-tuning of polymer compositions or adjustment of solvent qualities. Moreover, multistage silica regrowth of tripod and tetrapod allowed a fine control of the patch-to-particle size ratio ranging from 0.69 to 1.54. Intriguingly, patchy silica NPs (1-, 2-, 3-PSNs) rather than hybrid clusters are successfully used as templates for multistep regrowth experiments, leading to the formation of silica NPs with a new morphology and size controllable PVBA/PS patches. Last but not least, combined with mesoscale dynamics simulations, the self-assembly kinetics of 2-PSN and 3-PSN into linear colloidal polymers and honeycomb-like lattices are studied. This work paves a new avenue for constructing colloidal polymers with a well-defined sequence and colloidal crystals with a predetermined architecture.

Unraveling the Genetic Adaptations in Cell Surface Composition and Transporters of Lactiplantibacillus plantarum for Enhanced Acid Tolerance.

This study employed adaptive laboratory evolution to improve the acid tolerance of Lactiplantibacillus plantarum, a vital strain in food fermentation and a potential probiotic. Phenotype and genomic analyses identified the overexpression of stress response proteins, ATP synthases, and transporters as pivotal in conferring acid tolerance to the evolved strains. These adaptations led to a shorter lag phase, improved survival rates, and higher intracellular pH values compared to the wild-type strain under acid stress conditions. Additionally, the evolved strains showed an increased expression of genes in the fatty acid synthesis pathway, resulting in a higher production of unsaturated fatty acids. The changes in cell membrane composition possibly prevented H+ influx, while mutant genes related to cell surface structure contributed to observed elongated cells and thicker cell surface. These alterations in cell wall and membrane composition, along with improved transporter efficiency, were key factors contributing to the enhanced acid tolerance in the evolved strains.

Risk of Herpes Zoster Ophthalmicus Recurrence After Recombinant Zoster Vaccination.

Importance: The recombinant zoster vaccine (RZV) is currently recommended for immunocompetent adults aged 50 years or older and immunocompromised adults aged 19 years or older and is effective in preventing herpes zoster ophthalmicus (HZO). However, questions about the safety of RZV in patients with a history of HZO remain. Objective: To evaluate whether there is an increased risk of HZO recurrence after RZV in patients with a history of HZO. Design, Setting, and Participants: This retrospective cohort study used medical and outpatient pharmacy claims data for commercial and Medicare Advantage enrollees from the Optum Labs Data Warehouse. Patients with incident HZO from January 1, 2010, to December 31, 2021, were identified; the study period ended on March 31, 2022. The vaccinated group consisted of patients with at least 1 dose of RZV more than 90 days following the initial HZO diagnosis. The unvaccinated group consisted of patients without any record of RZV in the study period. Vaccinated and unvaccinated patients were matched using exact k:1 matching without replacement. Exposure: Recombinant zoster vaccination. Main Outcomes and Measures: The main outcome was the number of HZO recurrences with and without RZV exposure. Results: A total of 16 408 patients were included in the matched analysis, of whom 12 762 were unvaccinated (7806 [61.2%] female; mean [SD] age at diagnosis, 68.8 [10.3] years) and 3646 were vaccinated (2268 [62.2%] female; mean [SD] age at diagnosis, 67.4 [9.8] years). Within the primary risk period of 56 days after the index date (ie, the start of follow-up for the outcome), the incidence of HZO recurrence after any RZV exposure was 37.7 per 1000 person-years compared with 26.2 per 1000 person-years in the unexposed group. After controlling for race and ethnicity, inpatient stays, emergency department visits, concomitant vaccines, and eye care practitioner visits, the association between vaccination status and HZO exacerbation in the primary risk period had an adjusted hazard ratio for any RZV exposure of 1.64 (95% CI, 1.01-2.67; P = .04). Conclusions and Relevance: In this study, RZV exposure was associated with a higher likelihood of HZO recurrence in patients with a history of HZO compared with no RZV exposure. These findings support consideration that patients with a history of HZO may benefit from monitoring after receiving RZV in case of HZO recurrence.

An integrative database and its application for plant synthetic biology research.

Plant synthetic biology research requires diverse bioparts that facilitate the redesign and construction of new-to-nature biological devices or systems in plants. Limited by few well-characterized bioparts for plant chassis, the development of plant synthetic biology lags behind that of its microbial counterpart. Here, we constructed a web-based Plant Synthetic BioDatabase (PSBD), which currently categorizes 1677 catalytic bioparts and 384 regulatory elements and provides information on 309 species and 850 chemicals. Online bioinformatics tools including local BLAST, chem similarity, phylogenetic analysis, and visual strength are provided to assist with the rational design of genetic circuits for manipulation of gene expression in planta. We demonstrated the utility of the PSBD by functionally characterizing taxadiene synthase 2 and its quantitative regulation in tobacco leaves. More powerful synthetic devices were then assembled to amplify the transcriptional signals, enabling enhanced expression of flavivirus non-structure 1 proteins in plants. The PSBD is expected to be an integrative and user-centered platform that provides a one-stop service for diverse applications in plant synthetic biology research.

Correlation Between Life Satisfaction and Symptoms of ADHD in Dental Students: The Mediation of Resilience.

OBJECTIVE: This study explores the correlation between life satisfaction and ADHD symptoms. It also discusses whether resilience mediates the correlation between ADHD symptoms and life satisfaction. METHOD: We surveyed 297 dental students. A total of 291 completed a self-report scale consisting of the Adult ADHD Self-Report Scale, Wender Utah Rating Scale, Life Satisfaction Scale, and Conner-Davidson Resilience Scale. The study used hierarchical linear regression analysis, resampling, and asymptotic strategies for data processing. RESULTS: The ADHD screening results of the self-report scale were positive for 6.87% of the students. This positive rate differed among participants of diverse ages and varying paternal education levels. ADHD symptoms were negatively correlated with life satisfaction and resilience. Life satisfaction was observably positively associated with resilience. Resilience serves as a mediating role between life satisfaction and the two symptoms of ADHD. CONCLUSION: Resilience intervention programs can enhance the life satisfaction of dental students, especially those with positive ADHD symptoms screening.

A new high-resolution global topographic factor dataset calculated based on SRTM.

Topography is an important factor affecting soil erosion and is measured as a combination of the slope length and slope steepness (LS-factor) in erosion models, like the Chinese Soil Loss Equation. However, global high-resolution LS-factor datasets have rarely been published. Challenges arise when attempting to extract the LS-factor on a global scale. Furthermore, existing LS-factor estimation methods necessitate projecting data from a spherical trapezoidal grid to a planar rectangle, resulting in grid size errors and high time complexity. Here, we present a global 1-arcsec resolution LS-factor dataset (DS-LS-GS1) with an improved method for estimating the LS-factor without projection conversion (LS-WPC), and we integrate it into a software tool (LS-TOOL). Validation of the Himmelblau-Orlandini mathematical surface shows that errors are less than 1%. We assess the LS-WPC method on 20 regions encompassing 5 landform types, and R2 of LS-factor are 0.82, 0.82, 0.83, 0.83, and 0.84. Moreover, the computational efficiency can be enhanced by up to 25.52%. DS-LS-GS1 can be used as high-quality input data for global soil erosion assessment.

Risk of Herpes Zoster Ophthalmicus After COVID-19 Vaccination in a Large US Health Care Claims Database.

PURPOSE: Herpes zoster ophthalmicus (HZO) after COVID-19 vaccination has been reported in numerous case studies. However, no large-scale epidemiologic studies have been conducted to date. The purpose of this study was to determine whether COVID-19 vaccination is associated with an increased risk of HZO. DESIGN: Retrospective before-and-after risk interval analysis. METHODS: RESULTS: In total, 1,959,157 patients received a dose of a COVID-19 vaccine during the study period and met eligibility criteria. A total of 80 individuals without a prior history of HZO were included in the analysis because they developed HZO in the risk or control period. Patients had a mean age of 54.0 years (SD = 12.3 years). There were 45 cases of HZO in the risk interval after COVID-19 vaccination. There was not an increased risk of HZO after vaccination with BNT162b2 (IRR = 0.90, 95% CI: 0.49-1.69, P = .74), mRNA-1273 (IRR = 0.74, 95% CI: 0.36-1.54, P = .42), or Ad26.COV2.S (IRR = 0.50, 95% CI: 0.07-2.56, P = .42). CONCLUSIONS: This study found no evidence of increased risk of HZO after COVID-19 vaccination, providing reassurance for patients and providers who may be concerned about the safety profile of the COVID-19 vaccines.

Combined pollution characteristics and ecological risks of multi-pollutants in Poyang Lake.

Poyang Lake, the largest freshwater lake in China, faced severe ecological degradation in the past decade. Combined pollution of multi-pollutants may be one of the contributing factors. However, the characteristics of combined pollution and the ecological risks are still not clear. In this study, we used Polar Organic Chemical Integrative Sampler (POCIS), In Situ Bioassay Passive Sampling Device (ISBPSD) and conventional sampling methods, to study the toxic pollutants levels and the combined biological toxicity effects. The results showed that high levels of organochlorine pesticides (OCPs, averaged 162 ng/g) and polycyclic musk (PCM, averaged 53.6 ng/g) residues, as well as some metals such as nickel (Ni), lead (Pb) concentrations exceeded the relevant standard level in the sediment. The risk of combined pollution in the water was relatively low, but high risk was found in the sediments. According to the ISBPSD studies, the survival rates of species in the water and sediments were only 10.0-45.0% and 1.67-11.7% respectively, which was much lower than that reported in other typical basins of China. OCPs, PCMs, and certain metals such as Pb and Ni may be the key toxic pollutants causing biological toxicity effects in Poyang Lake.

Practice Patterns in the Initial Management of Herpes Zoster Ophthalmicus in the United States.

PURPOSE: The aims of this study were to examine the trends in the initial management of herpes zoster ophthalmicus (HZO) in the United States from 2010 to 2018 and compare them with the treatment preferences of corneal specialists. METHODS: A retrospective, observational deidentified cohort study was conducted on individuals enrolled in the OptumLabs Data Warehouse who had a new diagnosis of HZO from 1/1/2010 to 12/31/2018. An online survey ascertaining HZO management perspectives was distributed to The Cornea Society listserv. The main outcome assessed was proportion of cases with systemic antiviral prescriptions, eye care provider involvement, and follow-up visits after the initial HZO diagnosis. RESULTS: Approximately 50% of patients received systemic antivirals the day of initial HZO diagnosis or within 7 days (45.6% and 53.7%, respectively). Most initial diagnoses were made by ophthalmologists (45.0%), followed by optometrists (19.2%). Referral rate to ophthalmology within a year of initial diagnosis was 38.6%. 48.7% cases had at least 1 follow-up visit with any type of provider within 30 days. Our survey of corneal specialists found 97% would prescribe systemic antivirals to those with ocular involvement, but 66% would prescribe antivirals to those without ocular or eyelid involvement. Seventy percent supported all patients having follow-up with an eye care provider within a month. CONCLUSIONS: HZO antiviral therapies seem to be underprescribed in the United States, referral rates to ophthalmology are low, and follow-up is suboptimal, which are not aligned with recommendations from corneal specialists. More research is needed to establish standardized guidelines for treatment, referral, and follow-up with ophthalmology for HZO.

Immunosuppressive Medications and COVID-19 Outcomes in Patients with Noninfectious Uveitis in the Era of COVID-19 Vaccinations.

Purpose: To determine the risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in the era of COVID-19 vaccination among patients with noninfectious uveitis (NIU) taking immunosuppressive therapies. Design: Retrospective cohort study from July 1, 2021, to June 30, 2022, using data from the Optum Labs Data Warehouse (OLDW) de-identified claims database. Participants: Patients with a diagnosis of NIU from January 1, 2017, and who had ≥ 1 year of continuous enrollment in the OLDW. Methods: Incidence rates (IRs) were calculated for each COVID-19 outcome. Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of systemic corticosteroid (SC) exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models. Main Outcome Measures: Hazard ratios and IRs for COVID-19 infection, hospitalization, and death. Results: This study included 62 209 patients with NIU. A total of 12 895 (20.7%) were exposed to SCs during the risk period. Incidence rates were increased when exposed to SCs versus unexposed for all COVID-19 outcomes. Incidence rates were also increased for all COVID-19 outcomes when exposed to SCs without COVID-19 vaccination versus exposed to SCs with ≥ 1 vaccination. In adjusted models, SCs were associated with increased risk of COVID-19 infection (HR, 3.57; 95% confidence interval [CI], 3.24-3.93; P < 0.0001), hospitalization (HR, 2.75; 95% CI, 2.07-3.65; P < 0.0001), and death (HR, 2.49; 95% CI 1.29-4.82; P = 0.007). Incremental increases in SC dose were associated with a greater risk for all outcomes. Disease-modifying anti-rheumatic drugs were associated with a decreased risk of infection (HR, 0.84; 95% CI, 0.74-0.96; P = 0.01), and tumor necrosis factor-α inhibitors were associated with an increased risk of infection (HR, 1.18; 95% CI, 1.01-1.39; P = 0.04). Conclusions: Systemic corticosteroid exposure continues to be associated with greater risk of COVID-19 infection, hospitalization, and death among patients with NIU in an era of widespread COVID-19 vaccination. Unvaccinated individuals who are exposed to immunosuppressive treatments have a greater risk of severe outcomes. Coronavirus disease 2019 vaccination should be strongly encouraged in these patients. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Exploring mechanical properties and failure mechanisms of aramid and PBO crystals through molecular dynamics simulations.

Molecular dynamics simulations were used to analyze the mechanical properties and failure processes of poly(p-phenylene-terephthalamide) (PPTA), poly(p-phenylene-benzimidazole-terephthalamide) (PBIA), PBIA-PPTA (formed by 1:1 copolymerization of PPTA and PBIA), and poly(p-phenylene-benzobisoxazole) (PBO) crystals at different strain rates and temperatures. The failure stress and strain were found to be linear with the temperature and logarithmic strain rate. Moreover, based on the kinetic theory of fracture and the comprehensive simulation results, we formulated a model that describes the failure stress of the aforementioned crystals under varying strain rates and temperatures. Through the analysis of the failure process, we found that in PPTA, PBIA, and PBIA-PPTA crystals, the bond failure probability is correlated with the strain rate and temperature. The examination of bond lengths and angles unveiled that bonds with larger initial aligning angles are more susceptible to failure during the strain process. Intriguingly, the stretching process induced a conformational change in the PBO molecular chain, leading to a deviation from the linear relation in its stress-strain curve.

A combined analysis of multi-omics data reveals the prognostic values and immunotherapy response of LAG3 in human cancers.

Lymphocyte-activation gene 3 (LAG3) is a highly anticipated immune checkpoint in the context of cancer, exerting regulatory control over immune cell proliferation and function to reinforce the advancement of cancers. However, the comprehensive functional analysis of LAG3 across various cancer types remains undisclosed; thus, this study aims to investigate the pan-cancer expression profile of LAG3. We have investigated the expression profile, prognostic significance, and genetic alterations of LAG3 in various cancers while elucidating its characteristic in immune response regulation. Our findings demonstrated that elevated LAG3 expression is significantly associated with favorable prognosis in patients with cutaneous melanoma (SKCM), and it may be a potential biomarker for SKCM. Furthermore, multiple immune algorithms have highlighted the important regulatory role of LAG3 for the tumor-infiltrating immune cells including CD8 + T cells, B cells, dendritic cells (DCs), macrophages, and natural killer (NK) cells. We also examined the distribution of LAG3 at the single-cell level and explored its functional significance. A comprehensive and systematic analysis of LAG3 would facilitate a comprehensive evaluation of LAG3 in cancer biology and provide valuable insights for cancer management.

Isolation and proteomic study of fish liver lipid droplets.

Lipid droplets (LDs) are a neutral lipid storage organelle that is conserved in almost all species. Excessive storage of neutral lipids in LDs is directly associated with many metabolic syndromes. Zebrafish is a better model animal for the study of LD biology due to its transparent embryonic stage compared to other organisms. However, the study of LDs in fish has been difficult due to the lack of specific LD marker proteins and the limitation of purification technology. In this paper, the purification and proteomic analysis of liver LDs of fish including zebrafish and Carassius auratus were performed for the first time. 259 and 267 proteins were identified respectively. Besides most of the identified proteins were reported in previous LD proteomes of mammals, indicating the similarity between mammal and fish LDs. We also identified many unique proteins of liver LDs in fish that are involved in the regulation of LD dynamics. Through morphological and biochemical analysis, we found that the marker protein Plin2 of zebrafish LD was located on LDs in Huh7 cells. These results will facilitate further study of LDs in fish and liver metabolic diseases using fish as a model animal.

CCDC127 regulates lipid droplet homeostasis by enhancing mitochondria-ER contacts.

Lipid droplets (LDs) are both energy storage and signaling organelles playing important roles in various physiological and pathological conditions. The mitochondria-ER contacts have been implicated in regulating the homeostasis of lipid droplets. However, our knowledge about the molecular mechanism behind this regulation is still limited. In this study, we identified CCDC127, a previously uncharacterized protein, as a new regulator of LDs by enhancing the mitochondria-ER contact sites (MERCS). Knockdown and overexpression of CCDC127 in HeLa cells significantly change the LDs abundance in opposite directions, suggesting that CCDC127 positively regulates the LDs. Additional analysis showed that CCDC127 localizes on the outer membrane of mitochondria through its N-terminus and promotes mitochondria fragmentation. Importantly, knockdown or overexpression of CCDC127 significantly down- or up-regulates, respectively, the formation of MERCS. Further experiments showed that CCDC127 is required to stabilize the MERCS tether protein VAPA. And overexpression or knockdown of VAPA reversed the effects of CCDC127 reduction or overexpression on LDs. Finally, we demonstrated that knocking down CCDC127 in the mesenchymal stem cells reduced their differentiation towards adipocytes. These findings provide a new molecular connection between LD homeostasis and MERCS regulation.

Phase Interrogation Sensor Based on All-Dielectric BIC Metasurface.

The low performance of sensors based on an all-dielectric metasurface limits their application compared to metallic counterparts. Here, for the first time, an all-dielectric BIC (bound states in the continuum) metasurface is employed for highly sensitive phase interrogation refractive index sensing. The proposed sensor is well analyzed, fabricated, and characterized. Experimentally, a high-performance BIC-based microfluidic sensing chip with a Q factor of 1200 is achieved by introducing symmetry breaking. A refractive index sensor with high figure of merit of 418 RIU-1 is demonstrated, which is beneficial to the phase interrogation. Notably, we measure a record phase interrogation sensitivity of 2.7 × 104 deg/RIU to the refractive index, thus enabling the all-dielectric BIC to rival the refractive index detection capabilities of metal-based sensors such as surface plasmon resonance. This scheme establishes a pivotal role of the all-dielectric metasurface in the field of ultrahigh sensitivity sensors and opens possibilities for trace detection in biochemical analysis and environment monitoring.

Helical structures of achiral liquid crystals under cylindrical confinement.

Confined liquid crystals (LCs) exhibit complex and intriguing structures, which are fascinating fundamental problems in soft matter. The helical structure of cylindrical cavities is of great importance in LC studies, particularly for their application in optical devices. In this study, we employ molecular dynamics simulations to explore the behavior of achiral smectic-B LCs confined in narrow cylindrical cavities, where geometric frustration plays an important role. By increasing the cylinder size, LCs exhibit a transition from multi-helical to layered structures. Notably, we observe two stable structures, namely the helical structure and the layered structure, at moderate cylinder size. We also investigate the effects of the arrangement of cylindrical wall particles (hexagonal or square array) and anchoring strength on the LC structure. Our findings reveal that both the hexagonal array and strong anchoring strength promote the formation of helical structures. Our study provides novel insights into the confinement physics of LCs and highlights the potential for achieving helical structures in achiral LCs, which will expand the future applications of LCs.

Cerium added corn-based biochar as particle electrode for electrochemical oxidation industrial wastewater.

Three-dimensional (3D) electrochemical oxidation has become a popular advanced oxidation technology for wastewater treatment due to its various benefits. In this study, cerium (Ce) loaded biochar (Ce/BC) was used as a particle electrode to conduct the degradation of industrial wastewater released by the chemical industry. SEM, EDS, XRD, FTIR, XPS, and BET were used to characterize the properties of Ce/BC. The effects of some variables, including Ce loading (0-5%), pH (5-9), Ce/BC dosage (12.5-50.0 g/L), and working voltage (12-20 V), were evaluated with regard to COD elimination. The kinetics of COD oxidation and the energy consumption were carefully investigated. Tert-butanol significantly reduced the removal efficiency of COD, indicating that hydroxyl radicals generated during the process rather than direct electro-oxidation were the main mechanism for COD degradation. The treatment of industrial wastewater might benefit from the use of Ce/BC as particle electrode.