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BACKGROUND: Attribution models have been examined in Western countries. However, little is known about the applicability of the attitude-emotion-behavior model within Chinese culture. This study aimed to examine the association between familiarity, perceived dangerousness, fear, and social distance towards persons with mental illness (PMI) in the Chinese context. METHODS: An online cross-sectional survey was conducted from October to November 2022 in mainland China. A total of 1493 college students completed a questionnaire evaluating familiarity, perception of dangerousness, fear, and social distance regarding PMI. Path analysis was employed to validate the model proposed in this study. RESULTS: Participants expressed moderate to high levels of stigma towards PMI. Familiarity was negatively associated with social distance (p < 0.01). Participants who perceived PMI as dangerous were more prone to exhibit a reaction of fear (p < 0.001), consequently leading to social distance (p < 0.01). However, the mediating effect of perceived dangerousness and fear on the relationship between familiarity and social distance was not significant (p > 0.05). CONCLUSIONS: The results of this study provide support for Corrigan's attributional model of stigma in the Chinese context. Contact-based interventions for stigma reduction should emphasize multiple elements of contact, including the quality of contact, rather than familiarity.
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Objective: This study aimed to explore the impact of the COVID-19 pandemic on non-suicidal self-injury (NSSI) among youth students, and the mediating role of psychological factors in the relationship between the COVID-19 pandemic and NSSI. Method: An online survey was conducted at junior and senior high schools, as well as universities located in Jingzhou, Hubei Province, China between June 2021 and January 2022. The COVID-19 Impact Index was constructed using multiple correspondence analysis (MCA) method. The bootstrapping method was used for mediation analysis. Results: A total of 16025 youth participated in the study and 12507 youth (78.1%) finished the questionnaires. The COVID-19 Impact Index had a significantly positive effect on NSSI (r=0.16, p<0.001). The mediation analysis results showed that the COVID-19 Impact Index had a significant indirect effect on youth' NSSI (ß=0.0918, 95% CI [0.0788, 0.1048]), and this indirect effect was mainly achieved through affecting youth' anxiety, depression and post-traumatic stress disorder (PTSD). The mediation effect of anxiety on NSSI was 0.0584, the direct effect was 0.0334, and the mediation proportion was 63.6%. The mediation effect of depression on NSSI was 0.0668, the direct effect was 0.0250, and the mediation proportion was 72.8%. The mediation effect of PTSD on NSSI was 0.0640, the direct effect was 0.0278, and the mediation proportion was 69.7%. All the mediation effects, direct effects and total effects were statistically significant (p<0.001). Conclusion: The higher the impact of the COVID-19 Impact Index, the higher the prevalence of NSSI among youth students. Anxiety, depression and PTSD had mediated the relationship between the COVID-19 Impact Index and NSSI. It is suggested that specific health policies, mental health services and interventions should be developed to reduce the NSSI and improve mental health status among youth students during the COVID-19 pandemic.
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People with diabetes has an elevated risk of depression, and depression contributes to a worse prognosis for people with diabetes. Dietary antioxidants have been shown to reduce the risk of depression in the general population. Therefore, we hypothesized that dietary antioxidants would also help to reduce the risk of depression and all-cause mortality in people with prediabetes. A total of 8789 participants aged 20 years and older from the 2005-2018 National Health and Nutrition Examination Surveys who met the diagnostic criteria for prediabetes were included in our study. The associations between six dietary antioxidant intakes and the composite dietary antioxidant index (CDAI) with depression risk and all-cause mortality were assessed using weighted logistic and Cox regression. Possible nonlinear associations were further explored using restricted cubic spline. To ensure the reliability of the findings, the multiple imputations by chained equation were applied to missing covariates to avoid potential bias. Our study found that moderate dietary antioxidant intake prevents depression and improves prognosis in people with prediabetes. Moreover, a CDAI score near three allows for maximum benefit. Our findings could provide clues for early intervention in people with diabetes.
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Antioxidantes , Depresión , Estado Prediabético , Humanos , Estado Prediabético/mortalidad , Antioxidantes/administración & dosificación , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Encuestas Nutricionales , Dieta , Factores de Riesgo , Adulto JovenRESUMEN
Objective: To investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted. Methods: Students in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression. Results: Of the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one's education. Conclusions: Suicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.
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Liquid-phase electron microscopy (LP-EM) imaging has revolutionized our understanding of nanosynthesis and assembly. However, the current closed geometry limits its application for open systems. The ubiquitous physical process of the coffee-ring phenomenon that underpins materials and engineering science remains elusive at the nanoscale due to the lack of experimental tools. We introduce a quartz nanopipette liquid cell with a tunable dimension that requires only standard microscopes. Depending on the imaging condition, the open geometry of the nanopipette allows the imaging of evaporation-induced pattern formation, but it can also function as an ordinary closed-geometry liquid cell where evaporation is negligible despite the nano opening. The nano coffee-ring phenomenon was observed by tracking individual nanoparticles in an evaporating nanodroplet created from a thin liquid film by interfacial instability. Nanoflows drive the assembly and disruption of a ring pattern with the absence of particle-particle correlations. With surface effects, nanoflows override thermal fluctuations at tens of nanometers, in which nanoparticles displayed a "drunken man trajectory" and performed work at a value much smaller than kBT.
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Multicomponent macromolecular mixtures often form higher-order structures, which may display non-ideal mixing and aging behaviors. In this work, we first propose a minimal model of a quaternary system that takes into account the formation of a complex via a chemical reaction involving two macromolecular species; the complex may then phase separate from the buffer and undergo a further transition into a gel-like state. We subsequently investigate how physical parameters such as molecular size, stoichiometric coefficients, equilibrium constants, and interaction parameters affect the phase behavior of the mixture and its propensity to undergo aging via gelation. In addition, we analyze the thermodynamic stability of the system and identify the spinodal regions and their overlap with gelation boundaries. The approach developed in this work can be readily generalized to study systems with an arbitrary number of components. More broadly, it provides a physically based starting point for the investigation of the kinetics of the coupled complex formation, phase separation, and gelation processes in spatially extended systems.
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BACKGROUND: Previous studies on congenital heart diseases (CHD) associated with dextrocardia were based on selective patient databases and did not reflect the full spectrum of dextrocardia in the general population. Additionally, these studies had complex classification and presentation. Nor did these studies elaborate on the distribution of the associated CHD's complexity, the various segmental connections, and associated CHD among the four visceroatrial situs. METHODS: We retrospectively reviewed the medical records of 211 children with primary dextrocardia. We used a segmental approach to diagnose CHD. We then analyzed and compared the distribution of the above-mentioned issues among the four visceroatrial situs. RESULTS: Dextrocardia occurred most commonly with situs inversus (52.6%), followed by situs solitus (28.4%), asplenia (17.1%), and polysplenia (1.9%). Although some patients had a structurally normal heart (22.7%) or they were associated with simple CHD (17.5%), most patients had complex CHD (59.7%) consisting of a single ventricle (34.6%) or conotruncal anomaly (25.1%) (double-outlet right ventricle [7.6%], corrected transposition of the great arteries [6.2%], complete transposition of the great arteries [5.7%], tetralogy of Fallot [4.7%], etc.). Situs inversus or polysplenia had a higher prevalence of a structurally normal heart or associated with simple CHD, two patent atrioventricular (AV) valves connections, and biventricular AV connections. Situs solitus or asplenia had a higher prevalence of associated complex CHD, common AV valve connection, univentricular AV connection, pulmonary outflow tract obstruction, and anomalous pulmonary venous drainage. CONCLUSION: Our study finds that situs inversus is the most common visceroatrial situs in dextrocardia. Although some patients had a structurally normal heart or were associated with simple CHD, most patients have associated complex CHD consisting of a single ventricle or conotruncal anomaly. Dextrocardia is associated with a higher incidence of complex CHD in situs solitus and asplenia groups than in situs inversus and polysplenia groups.
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We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly assigned to one of three groups (high-dose, medium-dose, and low-dose) at a 3:1 ratio to receive one vaccine dose or placebo. Adverse events up to 28 days after each dose and serious adverse events up to 6 months after all doses were reported. Geometric mean titers and seroconversion rates were measured for anti-rotavirus neutralizing antibodies using microneutralization tests. The rates of total adverse events in the placebo group, low-dose group, medium-dose group, and high-dose group were 29.17 % (12.62 %-51.09 %), 12.50 % (2.66 %-32.36 %), 50.00 % (29.12 %-70.88 %), and 41.67 % (22.11 %-63.36 %), respectively, with no significant difference in the experimental groups compared with the placebo group. The results of the neutralizing antibody assay showed that in the adult group, the neutralizing antibody geometric mean titer at 28 days after full immunization in the low-dose group was 583.01 (95 % confidence interval [CI]: 447.12-760.20), that in the medium-dose group was 899.34 (95 % CI: 601.73-1344.14), and that in the high-dose group was 1055.24 (95 % CI: 876.28-1270.75). The GMT of serum-specific IgG at 28 days after full immunization in the low-dose group was 3444.26 (95 % CI: 2292.35-5175.02), that in the medium-dose group was 6888.55 (95 % CI: 4426.67-10719.6), and that in the high-dose group was 7511.99 (95 % CI: 3988.27-14149.0). The GMT of serum-specific IgA at 28 days after full immunization in the low-dose group was 2332.14 (95 % CI: 1538.82-3534.45), that in the medium-dose group was 4800.98 (95 % CI: 2986.64-7717.50), and that in the high-dose group was 3204.30 (95 % CI: 2175.66-4719.27). In terms of safety, adverse events were mainly Grades 1 and 2, indicating that the safety of the vaccine is within the acceptable range in the healthy adult population. Considering the GMT and positive transfer rate of neutralizing antibodies for the main immunogenicity endpoints in the experimental groups, it was initially observed that the high-dose group had higher levels of neutralizing antibodies than the medium- and low-dose groups in adults aged 18-49 years. This novel inactivated rotavirus vaccine was generally well-tolerated in adults, and the vaccine was immunogenic in adults (ClinicalTrials.gov number, NCT04626856).
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra Rotavirus , Vacunas de Productos Inactivados , Humanos , Adulto , Método Doble Ciego , Masculino , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Persona de Mediana Edad , Adulto Joven , Adolescente , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/efectos adversos , Vacunas contra Rotavirus/inmunología , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/efectos adversos , China , Inmunogenicidad Vacunal , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/inmunología , Rotavirus/inmunología , Voluntarios Sanos , Pruebas de NeutralizaciónRESUMEN
Vessel transplantation is currently considered the "gold standard" treatment for cardiovascular disease. However, ideal artificial vascular grafts should possess good biocompatibility and mechanical strength that match those of native autologous vascular tissue to promote in vivo tissue regeneration. In this study, a series of dynamic cross-linking double-network hydrogels and the resultant hydrogel tubes were prepared. The hydrogels (named PCO), composed of rigid poly(vinyl alcohol) (PVA), flexible carboxymethyl chitosan (CMCS), and a cross-linker of aldehyde-based ß-cyclodextrin (OCD), were formed in a double-network structure with multiple dynamical cross-linking including dynamic imine bonds, hydrogen bonds, and microcrystalline regions. The PCO hydrogels exhibited superior mechanical strength, good network stability, and fatigue resistance. Additionally, it demonstrated excellent cell and blood compatibility. The results showed that the introduction of CMCS/OCD led to a significant increase in the proliferation rate of endothelial cells seeded on the surface of the hydrogel. The hemolysis rate in the test was lower than 0.3%, and both protein adsorption and platelet adhesion were reduced, indicating an excellent anticoagulant function. The plasma recalcification time test results showed that endogenous coagulation was alleviated to some extent. When formed into blood vessels and incubated with blood, no thrombus formation was observed, and there was minimal red blood cell aggregation. Therefore, this novel hydrogel tube, with excellent mechanical properties, exhibits antiadhesive characteristics toward blood cells and proteins, as well as antithrombotic properties, making it hold tremendous potential for applications in the biomedical and engineering fields.
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Materiales Biocompatibles , Quitosano , Hidrogeles , Alcohol Polivinílico , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Humanos , Alcohol Polivinílico/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Prótesis Vascular , Ensayo de Materiales , beta-Ciclodextrinas/química , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Hemólisis/efectos de los fármacos , Animales , Adhesividad Plaquetaria/efectos de los fármacos , Reactivos de Enlaces Cruzados/químicaRESUMEN
Four previously undescribed isoprenoid flavonoids (2-5) were isolated from Sophora davidii, along with five known analogues. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and absolute configurations determined by theoretical calculations, including ECD and NMR calculation. The cytotoxic effects of the isolated compounds on human HT29 colon cancer cells were evaluated using the MTT assay, compound 1 exhibited cytotoxicity against human HT29 colon cancer cells with an IC50 value of 8.39 ± 0.09 µM. Studies conducted with compound 1 in HT29 cells demonstrated that it may induce apoptosis and autophagy in HT29 by promoting the phosphorylation of P38 MAPK and inhibiting the phosphorylation of Erk MAPK.
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Antineoplásicos Fitogénicos , Apoptosis , Autofagia , Flavonoides , Sophora , Humanos , Sophora/química , Autofagia/efectos de los fármacos , Apoptosis/efectos de los fármacos , Células HT29 , Estructura Molecular , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , China , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Terpenos/farmacología , Terpenos/aislamiento & purificación , FosforilaciónRESUMEN
With the diversified development of big data, detection and precision guidance technologies, electromagnetic (EM) functional materials and devices serving multiple spectrums have become a hot topic. Exploring the multispectral response of materials is a challenging and meaningful scientific question. In this study, MXene/TiO2 hybrids with tunable conduction loss and polarization relaxation are fabricated by in situ atomic reconstruction engineering. More importantly, MXene/TiO2 hybrids exhibit adjustable spectral responses in the GHz, infrared and visible spectrums, and several EM devices are constructed based on this. An antenna array provides excellent EM energy harvesting in multiple microwave bands, with |S11| up to - 63.2 dB, and can be tuned by the degree of bending. An ultra-wideband bandpass filter realizes a passband of about 5.4 GHz and effectively suppresses the transmission of EM signals in the stopband. An infrared stealth device has an emissivity of less than 0.2 in the infrared spectrum at wavelengths of 6-14 µm. This work can provide new inspiration for the design and development of multifunctional, multi-spectrum EM devices.
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BACKGROUND: Gastric cancer (GC) lacks serum biomarkers with clinical diagnostic value. Multi-omics analysis is an important approach to discovering cancer biomarkers. This study aimed to identify and validate serum biomarkers for GC diagnosis by cross-analysis of proteomics and transcriptomics datasets. METHODS: A cross-omics analysis was performed to identify overlapping differentially expressed genes (DEGs) between our previous aptamer-based GC serum proteomics dataset and the GC tissue RNA-Seq dataset in The Cancer Genome Atlas (TCGA) database, followed by lasso regression and random forest analysis to select key overlapping DEGs as candidate biomarkers for GC. The mRNA levels and diagnostic performance of these candidate biomarkers were analyzed in the original and independent GC datasets to select valuable candidate biomarkers. The valuable candidate biomarkers were subjected to bioinformatics analysis to select those closely associated with the biological behaviors of GC as potential biomarkers. The clinical diagnostic value of the potential biomarkers was validated using serum samples, and their expression levels and functions in GC cells were validated using in vitro cell experiments. RESULTS: Four candidate biomarkers (ILF2, PGM2L1, CHD7, and JCHAIN) were selected. Their mRNA levels differed significantly between tumor and normal tissues and showed different diagnostic performances for GC, with areas under the receiver operating characteristic curve (AUROCs) of 0.629-0.950 in the TCGA dataset and 0.736-0.840 in the Gene Expression Omnibus (GEO) dataset. In the bioinformatics analysis, only ILF2 (interleukin enhancer-binding factor 2) gene levels were associated with immune cell infiltration, some checkpoint gene expression, chemotherapy sensitivity, and immunotherapy response. Serum levels of ILF2 were higher in GC patients than in controls, with an AUROC of 0.944 for the diagnosis of GC, and it was also detected in the supernatants of GC cells. Knockdown of ILF2 by siRNA significantly reduced the proliferation and colony formation of GC cells. Overexpression of ILF2 significantly promotes the proliferation and colony formation of gastric cancer cells. CONCLUSIONS: Trans-omics analysis of proteomics and transcriptomics is an efficient approach for discovering serum biomarkers, and ILF2 is a potential diagnostic biomarker and therapeutic target of gastric cancer.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Biomarcadores de Tumor/metabolismo , Perfilación de la Expresión Génica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína del Factor Nuclear 45/genéticaRESUMEN
Fenton catalytic medicine that catalyzes the production of ·OH without external energy input or oxygen as a substrate has reshaped the landscape of conventional cancer therapy in recent decades, yet potential biosafety concerns caused by non-safety-approved components restrict their clinical translation from the bench to the bedside. Herein, to overcome this dilemma, we elaborately utilizate safety-approved hetastarch, which has been extensively employed in the clinic as a plasma substitute, as a stabilizer participating in the copper chloride-initiated polymerization of pyrrole monomer before loading it with DOX. The constructed DOX-loaded hetastarch-doped Cu-based polypyrrole (HES@CuP-D) catalyzes the excess H2O2 in tumor cells to ·OH through a Cu+-mediated Fenton-like reaction, which not only causes oxidative damage to tumor cells but also leads to the structural collapse and DOX release. Additionally, HES@CuP-D together with laser irradiation reinforces tumor killing efficiency by hyperthermia-enhanced catalytic activity and -accelerated drug release. As a result, the developed HES@CuP-D provides a promising strategy for Fenton catalytic therapy with negligible toxicity to the body.
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BACKGROUND: Live attenuated vaccines may be used to prevent nontargeted diseases such as lower respiratory tract infections (LRTIs) due to their nonspecific effects (NSEs). OBJECTIVE: We aimed to analyze the NSEs of the Japanese encephalitis vaccine on pediatric LRTIs in children aged 25 months to 35 months. METHODS: A retrospective cohort study was conducted by using a population-based electronic health record database in Zhejiang, China. Enrolled participants were children born from January 1, 2017, to December 31, 2017, and who were inoculated with the live-attenuated Japanese encephalitis vaccine (JE-L) or inactivated Japanese encephalitis vaccine (JE-I) as the most recent vaccine at 24 months of age. The study was carried out between January 1, 2019, and December 31, 2019. All inpatient and outpatient hospital visits for LRTIs among children aged 25 months to 35 months were recorded. The Andersen-Gill model was used to assess the NSEs of JE-L against LRTIs in children and compared with those of JE-I as the most recent vaccine. RESULTS: A total of 810 children born in 2017 were enrolled, of whom 585 received JE-L (JE-L cohort) and 225 received JE-I (JE-I cohort) as their last vaccine. The JE-L cohort showed a reduced risk of LRTIs (adjusted hazard ratio [aHR] 0.537, 95% CI 0.416-0.693), including pneumonia (aHR 0.501, 95% CI 0.393-0.638) and acute bronchitis (aHR 0.525, 95% CI 0.396-0.698) at 25 months to 35 months of age. The NSEs provided by JE-L were especially pronounced in female children (aHR 0.305, 95% CI 0.198-0.469) and children without chronic diseases (aHR 0.553, 95% CI 0.420-0.729), without siblings (aHR 0.361, 95% CI 0.255-0.511), with more than 30 inpatient and outpatient hospital visits prior to 24 months of age (aHR 0.163, 95% CI 0.091-0.290), or with 5 to 10 inpatient and outpatient hospital visits due to infectious diseases prior to 24 months old (aHR 0.058, 95% CI 0.017-0.202). CONCLUSIONS: Compared with JE-I, receiving JE-L as the most recent vaccine was associated with lower risk of inpatient and outpatient hospital visits for LRTIs among children aged 25 months to 35 months. The nature of NSEs induced by JE-L should be considered for policymakers and physicians when recommending JE vaccines to those at high risk of infection from the Japanese encephalitis virus.
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Vacunas contra la Encefalitis Japonesa , Infecciones del Sistema Respiratorio , Vacunas , Humanos , Femenino , Niño , Preescolar , Vacunas contra la Encefalitis Japonesa/uso terapéutico , Estudios Retrospectivos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/prevención & control , China/epidemiologíaRESUMEN
A new scheme presents MEMS-based LiDAR with synchronized dual-laser beams for detection range enhancement and precise point-cloud data without using higher laser power. The novel MEMS-based LiDAR module uses the principal laser light to build point-cloud data. In addition, an auxiliary laser light amplifies the single-noise ratio to enhance the detection range. This LiDAR module exhibits the field of view (FOV), angular resolution, and maximum detection distance of 45° (H) × 25° (V), 0.11° (H) × 0.11° (V), and 124 m, respectively. The maximum detection distance is enhanced by 16% from 107 m to 124 m with a laser power of 1 W and an additional auxiliary laser power of 0.355 W. Furthermore, the simulation results show that the maximum detection distance can be up to 300 m with laser power of 8 W and only 6 W if the auxiliary laser light of 2.84 W is used, which is 35.5% of the laser power. This result indicates that the synchronized dual-laser beams can achieve long detection distance and reduce laser power 30%, hence saving on the overall laser system costs. Therefore, the proposed LiDAR module can be applied for a long detection range in autonomous vehicles without requiring higher laser power if it utilizes an auxiliary laser light.
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Many biomolecular condensates, including transcriptional condensates, are formed in elastic mediums. In this work, we study the nonequilibrium condensate dynamics in a chromatin-like environment modeled as a heterogeneous elastic medium. We demonstrate that the ripening process in such an elastic medium exhibits a temporal power-law scaling of the average condensate radius, depending on the local stiffness distribution and different from Ostwald ripening. Moreover, we incorporate an active process to model the dissolution of transcriptional condensates upon RNA accumulation. Intriguingly, three types of kinetics of condensate growth emerge, corresponding to constitutively expressed, transcriptional-bursting, and silenced genes. Furthermore, the simulated burst frequency decreases exponentially with the local stiffness, through which we infer a lognormal distribution of local stiffness in living cells using the transcriptome-wide distribution of burst frequency. Under the inferred stiffness distribution, the simulated distributions of bursting kinetic parameters agree reasonably well with the experimental data. Our findings reveal the interplay between biomolecular condensates and elastic mediums, yielding far-reaching implications for gene expression.
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Condensados Biomoleculares , Cuerpos Nucleares , Cromatina , Elasticidad , CinéticaRESUMEN
A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities inâ vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96â µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.
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Amidas , Ciclooxigenasa 2 , Lipopolisacáridos , Simulación del Acoplamiento Molecular , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico , Sulfonamidas , Animales , Ratones , Células RAW 264.7 , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Ciclooxigenasa 2/metabolismo , Amidas/química , Amidas/farmacología , Amidas/síntesis química , Relación Estructura-Actividad , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/síntesis química , Estructura Molecular , Relación Dosis-Respuesta a Droga , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/químicaRESUMEN
Continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants urges the development of new vaccines. We assessed the safety and immunogenicity of SYS6006.32, a bivalent vaccine (XBB.1.5/BQ.1), in healthy adults who had received SARS-CoV-2 primary vaccination. In a randomised, double-blinded, active-controlled trial, 200 participants were randomised to receive one dose of SYS6006.32 (N = 100) or a prototype-based, monovalent control vaccine SYS6006 (N = 100). Adverse events (AEs) were collected through the study. Immunogenicity was assessed by live-virus neutralising antibody (Nab) and pseudovirus Nab. 61 (61.0 %) and 60 (60.0 %) participants reported AE in the SYS6006.32 and SYS6006 groups, respectively. Most AEs were grade 1 or 2. Pain and fever were the most common injection-site and systemic AEs, respectively. No serious AEs were observed. SYS6006.32 heterologous boosting induced robust Nab responses against BA.5, XBB.1.5 and EG.5 with live-virus Nab geometric mean titres (GMTs) increased by 17.1-, 34.0-, and 48.0-fold, and pseudovirus Nab GMTs increased by 12.2-, 32.0-, and 35.1-fold, respectively, 14 days after vaccination. SYS6006.32 demonstrated a superior immunogenicity to SYS6006. SYS6006.32 also induced robust pseudovirus Nab responses against XBB.1.16, XBB.2.3, and BA.2.86, with GMTs 3- to 6-fold higher than those induced by SYS6006. In conclusion, SYS6006.32 showed good safety profile and superior immunogenicity to the monovalent vaccine SYS6006.