Attentional control influence habituation through modulation of connectivity patterns within the prefrontal cortex: Insights from stereo-EEG.

Attentional control, guided by top-down processes, enables selective focus on pertinent information, while habituation, influenced by bottom-up factors and prior experiences, shapes cognitive responses by emphasizing stimulus relevance. These two fundamental processes collaborate to regulate cognitive behavior, with the prefrontal cortex and its subregions playing a pivotal role. Nevertheless, the intricate neural mechanisms underlying the interaction between attentional control and habituation are still a subject of ongoing exploration. To our knowledge, there is a dearth of comprehensive studies on the functional connectivity between subsystems within the prefrontal cortex during attentional control processes in both primates and humans. Utilizing stereo-electroencephalogram (SEEG) recordings during the Stroop task, we observed top-down dominance effects and corresponding connectivity patterns among the orbitofrontal cortex (OFC), the middle frontal gyrus (MFG), and the inferior frontal gyrus (IFG) during heightened attentional control. These findings highlighting the involvement of OFC in habituation through top-down attention. Our study unveils unique connectivity profiles, shedding light on the neural interplay between top-down and bottom-up attentional control processes, shaping goal-directed attention.

Deciphering the omicron variant: integrated omics analysis reveals critical biomarkers and pathophysiological pathways.

BACKGROUND: The rapid emergence and global dissemination of the Omicron variant of SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores the urgent need for an enhanced understanding of Omicron's pathophysiological mechanisms to guide clinical management and shape public health strategies. Our study is aimed at deciphering the intricate molecular mechanisms underlying Omicron infections, particularly focusing on the identification of specific biomarkers. METHODS: This investigation employed a robust and systematic approach, initially encompassing 15 Omicron-infected patients and an equal number of healthy controls, followed by a validation cohort of 20 individuals per group. The study's methodological framework included a comprehensive multi-omics analysis that integrated proteomics and metabolomics, augmented by extensive bioinformatics. Proteomic exploration was conducted via an advanced Ultra-High-Performance Liquid Chromatography (UHPLC) system linked with mass spectrometry. Concurrently, metabolomic profiling was executed using an Ultra-Performance Liquid Chromatography (UPLC) system. The bioinformatics component, fundamental to this research, entailed an exhaustive analysis of protein-protein interactions, pathway enrichment, and metabolic network dynamics, utilizing state-of-the-art tools such as the STRING database and Cytoscape software, ensuring a holistic interpretation of the data. RESULTS: Our proteomic inquiry identified eight notably dysregulated proteins (THBS1, ACTN1, ACTC1, POTEF, ACTB, TPM4, VCL, ICAM1) in individuals infected with the Omicron variant. These proteins play critical roles in essential physiological processes, especially within the coagulation cascade and hemostatic mechanisms, suggesting their significant involvement in the pathogenesis of Omicron infection. Complementing these proteomic insights, metabolomic analysis discerned 146 differentially expressed metabolites, intricately associated with pivotal metabolic pathways such as tryptophan metabolism, retinol metabolism, and steroid hormone biosynthesis. This comprehensive metabolic profiling sheds light on the systemic implications of Omicron infection, underscoring profound alterations in metabolic equilibrium. CONCLUSIONS: This study substantially enriches our comprehension of the physiological ramifications induced by the Omicron variant, with a particular emphasis on the pivotal roles of coagulation and platelet pathways in disease pathogenesis. The discovery of these specific biomarkers illuminates their potential as critical targets for diagnostic and therapeutic strategies, providing invaluable insights for the development of tailored treatments and enhancing patient care in the dynamic context of the ongoing pandemic.

Development of a Me2SO-free cryopreservation medium and its long-term cryoprotection on the CAR-NK cells.

Cryopreservation is a crucial step in the supply process of off-the-shelf chimeric antigen receptor engineered natural killer (CAR-NK) cell products. Concerns have been raised over the clinical application of dimethyl sulfoxide (Me2SO) due to the potential for adverse reactions following infusion and limited cell-specific cytotoxic effects if misapplied. In this study, we developed a Me2SO-free cryopreservation medium specifically tailored for CAR-NK cells to address this limitation. The cryopreservation medium was formulated using human serum albumin (HSA) and glycerol as the base components. Following initial screening of seven clinically-compatible solutions, four with cryoprotective properties were identified. These were combined and optimized into a single formulation: IF-M. The viability, phenotype, and function of CAR-NK cells were evaluated after short-term and long-term cryopreservation to assess the effectiveness of IF-M, with Me2SO serving as the control group. The viability and recovery of CAR-NK cells in the IF-M group were significantly higher than those in the Me2SO group within 90 days of cryopreservation. Moreover, after 1 year of cryopreservation the cytotoxic capacity of CAR-NK cells cryopreserved with IF-M was comparable to that of fresh CAR-NK cells and significantly superior to that of CAR-NK cells cryopreserved in Me2SO. The CD107a expression intensity of CAR-NK cells in IF-M group was significantly higher than that of Me2SO group. No statistical differences were observed in other indicators under different cryopreservation times. These results underscore the robustness of IF-M as a suitable replacement for traditional Me2SO-based cryopreservation medium for the long-term cryopreservation and clinical application of off-the-shelf CAR-NK cells.

Utilizing support vector machines to foster sustainable development and innovation in the clean energy sector via green finance.

As the global demand for clean energy continues to grow, the sustainable development of clean energy projects has become an important topic of research. in order to optimize the performance and sustainability of clean energy projects, this work explores the environmental and economic benefits of the clean energy industry. through the use of Support Vector Machine (SVM) Multi-factor models and a bi-level multi-objective approach, this work conducts comprehensive assessment and optimization. with wind power base a as a case study, the work describes the material consumption of wind turbines, transportation energy consumption and carbon dioxide (CO2) emissions, and infrastructure material consumption through descriptive statistics. Moreover, this work analyzes the characteristics of different wind turbine models in depth. On one hand, the SVM multi-factor model is used to predict and assess the profitability of Wind Power Base A. On the other hand, a bi-level multi-objective approach is applied to optimize the number of units, internal rate of return within the project, and annual average equivalent utilization hours of the Wind Power Base A. The research results indicate that in March, the WilderHill New Energy Global Innovation Index (NEX) was 0.91053, while the predicted value of the SVM multi-factor model was 0.98596. The predicted value is slightly higher than the actual value, demonstrating the model's good grasp of future returns. The cumulative rate of return of Wind Power Base A is 18.83%, with an annualized return of 9.47%, exceeding the market performance by 1.68%. Under the optimization of the bi-level multi-objective approach, the number of units at Wind Power Base A decreases from the original 7004 to 5860, with total purchase and transportation costs remaining basically unchanged. The internal rate of return of the project increases from 8% to 9.3%, and the annual equivalent utilization hours increase to 2044 h, comprehensively improving the investment return and utilization efficiency of the wind power base. Through optimization, significant improvements are achieved in terAs the global demand for clean energy continues to grow, the sustainable development of clean energy projects has become an important topic of research. In order to optimize the performance and sustainability of clean energy projects, this work explores the environmental and economic benefits of the clean energy industry. Through the use of Support Vector Machine (SVM) multi-factor models and a bi-level multi-objective approach, this work conducts comprehensive assessment and optimization. With Wind Power Base A as a case study, the work describes the material consumption of wind turbines, transportation energy consumption and carbon dioxide (CO2) emissions, and infrastructure material consumption through descriptive statistics. Moreover, this work analyzes the characteristics of different wind turbine models in depth. On one hand, the SVM multi-factor model is used to predict and assess the profitability of Wind Power Base A. On the other hand, a bi-level multi-objective approach is applied to optimize the number of units, internal rate of return within the project, and annual average equivalent utilization hours of the Wind Power Base A. The research results indicate that in March, the WilderHill New Energy Global Innovation Index (NEX) was 0.91053, while the predicted value of the SVM multi-factor model was 0.98596. The predicted value is slightly higher than the actual value, demonstrating the model's good grasp of future returns. The cumulative rate of return of Wind Power Base A is 18.83%, with an annualized return of 9.47%, exceeding the market performance by 1.68%. Under the optimization of the bi-level multi-objective approach, the number of units at Wind Power Base A decreases from the original 7004 to 5860, with total purchase and transportation costs remaining basically unchanged. The internal rate of return of the project increases from 8% to 9.3%, and the annual equivalent utilization hours increase to 2044 h, comprehensively improving the investment return and utilization efficiency of the wind power base. Through optimization, significant improvements are achieved in terms of the number of units, internal rate of return within the project, and annual average equivalent utilization hours at Wind Power Base A. The number of units decreases to 5860, with total purchase and transportation costs remaining basically unchanged, the internal rate of return increases to 9.3%, and annual equivalent utilization hours increase to 2044 h. Energy consumption and CO2 emissions are significantly reduced, with energy consumption decreasing by 0.68 × 109 kgce and CO2 emissions decreasing by 1.29 × 109 kg. The optimization effects are mainly concentrated in the production and installation stages, with emission reductions achieved through the recycling and disposal of materials consumed in the early stages. In terms of investment benefits, environmental benefits are enhanced, with a 13.93% reduction in CO2 emissions. Moreover, there is improved energy efficiency, with the energy input-output ratio increasing from 7.73 to 9.31. This indicates that the Wind Power Base A project has significant environmental and energy efficiency advantages in the clean energy industry. This work innovatively provides a comprehensive assessment and optimization scheme for clean energy projects and predicts the profitability of Wind Power Base A using SVM multi-factor models. Besides, this work optimizes key parameters of the project using a bi-level multi-objective approach, thus comprehensively improving the investment return and utilization efficiency of the wind power base. This work provides innovative methods and strong data support for the development of the clean energy industry, which is of great significance for promoting sustainable development under the backdrop of green finance.

Evaluation of the clinical performance of multiple serum sIgE detection systems based on component-resolved diagnosis.

BACKGROUND: Serum allergen-specific IgE (sIgE) detection is an important tool in the diagnosis of allergic diseases. However, the absence of international standards for sIgE detection systems raises questions about the comparability of different systems. OBJECTIVE: This study aims to evaluate three common allergen sIgE detection systems, with a primary focus on detecting dust mite allergens. METHODS: We recruited 85 children with rhinitis and 15 healthy control children. The subjects underwent testing with three different sIgE detection systems, including magnetic particle flow fluorescence, magnetic particle chemiluminescence, and protein chip, to detect sIgE levels to HDM extracts. In addition, skin prick testing (SPT) was conducted, and protein chip technology was performed to measure sIgE levels to component proteins. RESULTS: Our findings reveal strong consistency between SPT and the three in vitro detection systems, with consistency exceeding 71.76% for dust mite allergens. Moreover, there was excellent consistency and RAST class consistency among the three in vitro detection systems, with scores exceeding 94.12% and 89.00%, respectively. And for the 13 additional allergens crude extracts sIgE simultaneously detected by systems 1 and 2, the results showed that the consistency of both systems was above 87.00%, and the RAST class consistency was above 82.00%. CONCLUSION: The three serum sIgE detection systems exhibited an approximate 80% concordance rate with SPT in identifying dust mite allergens. Furthermore, these systems demonstrated excellent consistency and RAST class consistency among themselves. These findings suggest that the three assays introduced in this study are interchangeable in allergen diagnosis.

Dual-polarization interferometric fiber optic gyroscope based on a four-port circulator.

The dual-polarization interferometric fiber optic gyroscope (IFOG) has been studied for many years and achieved remarkable performance. In this study, we propose a novel dual-polarization IFOG configuration based on a four-port circulator, in which the polarization coupling errors and the excess relative intensity noise are well handled meanwhile. Experimental measurements of the short-term sensitivity and long-term drift using a fiber coil with a length of 2 km and a diameter of 14 cm show that the angle random walk of 5.0×10-5∘/h and bias instability of 9.0 × 10-5 °/h are achieved. Moreover, the root power spectrum density of 20n r a d/s/H z is almost flat from 0.001 Hz to 30 Hz. We believe this dual-polarization IFOG is a preferred candidate for the reference-grade performance IFOG.

Vector solitonic pulses excitation in microresonators via free carrier effects.

We numerically investigate the excitation of vector solitonic pulse with orthogonally polarized components via free-carrier effects in microresonators with normal group velocity dispersion (GVD). The dynamics of single, dual and oscillated vector pulses are unveiled under turn-key excitation with a single frequency-fixed CW laser source. Parameter spaces associated with detuning, polarization angle, interval between the pumped orthogonal resonances and pump amplitude have been revealed. Different vector pulse states can also be observed exploiting the traditional pump scanning scheme. Simultaneous and independent excitation regimes are identified due to varying interval of the orthogonal pump modes. The nonlinear coupling between two modes contributes to the distortion of the vector pulses' profile. The free-carrier effects and the pump polarization angle provide additional degrees of freedom for efficiently controlling the properties of the vector solitonic microcombs. Moreover, the crucial thermal dynamics in microcavities is discussed and weak thermal effects are found to be favorable for delayed vector pulse formation. These findings reveal complex excitation mechanism of solitonic structures and could provide novel routes for microcomb generation.

Angular accelerometer based on a dual-polarization fiber-optic Sagnac interferometer.

High-performance angular accelerometers are essential for precise dynamics control of aircraft, satellites, etc. Here, we propose, for the first time to the best of our knowledge, an angular accelerometer based on a dual-polarization fiber-optic Sagnac interferometer, which exhibits relatively high sensitivity and a broad bandwidth. The experimental results show that the angular accelerometer achieves a flat frequency response in the bandwidth range of 0.01-100 Hz. The sensitivity reaches 6.6 × 10-8 rad/s2/Hz. In addition, the proposed fiber-optic angular accelerometer does not rely on any mechanical structure and has strong environmental adaptability. This research provides a feasible solution for the design and implementation of new high-performance angular accelerometers, which contributes to their development in the fields of inertial navigation and rotational seismology.

Interferometric fiber-optic gyroscope based on mode-division multiplexing.

The interferometric fiber-optic gyroscope (IFOG) is widely used in the fields of inertial navigation and rotational seismology. A direct way to improve the sensitivity of the IFOG is to increase the length of the sensing fiber, but this increases the cost and size of the gyroscope. Here, we propose an IFOG based on mode-division multiplexing (MDM), which exhibits relatively high performance. The experimental results show that, the proposed IFOG is improved to twice as much in terms of sensitivity, angle random walk, and bias instability with the use of MDM. This research provides a novel, to the best of our knowledge, solution for the design and implementation of low-cost, high-sensitivity IFOGs, which could contribute to their application in a wider range of fields.

Compensation of scale factor nonlinear error introduced by harmonic distortion for open-loop fiber optic gyroscopes.

The scale factor (SF) of a gyroscope is the ratio of the detection output rotational rate and the input, and is expected to be a constant. However, for open-loop interferometric fiber optic gyroscopes (IFOGs) with sinusoidal modulation, harmonic amplitudes are inevitably affected by detection defects, such as nonuniform frequency response of the photodetector or unequal gain of amplification circuits. As a result, harmonic distortion leads to SF nonlinearity, which seriously hinders the accuracy of high-precision gyroscopes. In this Letter, the theoretical form of the SF error introduced by harmonic distortion of open-loop gyroscopes is analyzed, and an effective and simple compensation method is proposed. Instead of traversing the whole dynamic range, the proposed method simplifies the calibration pretest, where only a section of the dynamic range needs to be tested. Experimental results on an open-loop IFOG prototype show that, with our proposed method, the SF nonlinear error is suppressed to 2.5 ppm within the range -300 to +300∘/s, which is 33 times less than that before compensation.

Multi-omics analyses of serum metabolome, gut microbiome and brain function reveal dysregulated microbiota-gut-brain axis in bipolar depression.

The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundii and Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederiksenii and Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacae and Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.

Promotion of bio-oil production from the microwave pyrolysis of cow dung using pretreated red mud as a bifunctional additive: Parameter optimization, energy efficiency evaluation, and mechanism analysis.

To address the issues of high oxygen content and energy consumption in the microwave-assisted pyrolysis of biomass for biofuel production, this study used high-temperature pretreated red mud (RM) as an additive. The pretreated RM exhibited dual functionalities, namely microwave absorption and catalytic properties, during the microwave-assisted pyrolysis of cow dung (CD). This study also evaluated the optimization potential of energy recovery efficiency. The results showed that the addition of pretreated RM significantly increased the oil yield during the microwave-assisted pyrolysis of CD. The highest oil yield (59.63%) was obtained via the microwave-assisted pyrolysis of CD over catalysis with RM pretreated at 750 °C (RM750). Through the optimization of the RM750-to-CD mixing ratio, optimal oil quality and energy recovery efficiency were achieved. At a mixing ratio of 1:1, the pyrolysis oil featured the highest aromatic hydrocarbon content and lowest acid content. The high-temperature pretreatment of RM increased the Fe2O3 content, which enhanced the dielectric properties and magnetic loss ability of the reactants. This resulted in localized high temperatures and the formation of "hot spots," which can promote the deoxygenation and hydrogenation reactions of oil. Consequently, the lower heating rate of oil increased from 35.12 to 40.11 MJ kg-1. The released oxygen escaped in the form of CO. In addition, pyrolytic char was used as an in situ microwave absorbing material owing to its increased Fe2O3 content and graphitization degree, leading to an increase in energy recovery efficiency from 4.71% to 9.98%. This study provides valuable guidance for the efficient utilization of diversified solid wastes and demonstrates the potential application of microwave-assisted pyrolysis technology in the resource utilization of solid wastes.

Preparation of high performance porous carbon by microwave synergistic nitrogen/phosphorus doping for efficient removal of Cu2+ via capacitive deionization.

Sargassum biochar has potential advantages as an electrode material due to its natural microscopic pore channels. However, conventional pyrolysis method is prone to thermal damage to the biochar, and incapable to form a complete pore structure resulting in poor biochar electrode performance. In this study, a strategy of microwave pyrolysis coupled with KOH activation was used to prepare nitrogen/phosphorus double-doped graded porous biochar (STC) using ammonium dihydrogen phosphate as dopant. The carbon material STC-1.24-800 prepared by the optimal parameters had a high specific surface area (SSA) of 1367.6 m2 g -1 and a total pore volume of 1.499 cm3 g-1. The precise inside-out heating characteristics of microwave facilitated the generation of suitable meso-micropore distribution ratios in carbon, and the graded porous structure provided abundant active sites for charge accumulation and ion diffusion. The doped nitrogen/phosphorus atoms responding to the microwave field, generated spin to promote microwave absorption, introducing surface structural defects to produce electron density differences. The change in the nature of the electron donor and its electron density enhanced the electrical conductivity and chemical stability of STC. Nitrogen/phosphorus polar surface functional groups improved hydrophilicity and wettability. STC-1.24-800 had a higher specific capacitance of 531 F g-1 and exhibits great cycle performance in capacitive deionization (CDI) applications (1.0 V, 50 mg L-1 Cu2+) as well as adsorption performance (56.16 mg g -1). The present work can provide a novel feasible idea for preparing diatomically doped graded porous biochar for CDI electrode application by microwave irradiation.

Integrative omics analysis identifies biomarkers of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic progressive pulmonary fibrosis and a poor prognosis. Genetic studies, including transcriptomic and proteomics, have provided new insight into revealing mechanisms of IPF. Herein we provided a novel strategy to identify biomarkers by integrative analysis of transcriptomic and proteomic profiles of IPF patients. We examined the landscape of IPF patients' gene expression in the transcription and translation phases and investigated the expression and functions of two new potential biomarkers. Differentially expressed (DE) mRNAs were mainly enriched in pathways associated with immune system activities and inflammatory responses, while DE proteins are related to extracellular matrix production and wound repair. The upregulated genes in both phases are associated with wound repair and cell differentiation, while the downregulated genes in both phases are associated with reduced immune activities and the damage of the alveolar tissues. On this basis, we identified thirteen potential marker genes. Among them, we validated the expression changes of butyrophilin-like 9 (BTNL9) and plasmolipin (PLLP) and investigated their functional pathways in the IPF mechanism. Both genes are downregulated in the tissues of IPF patients and Bleomycin-induced mice, and co-expression analysis indicates that they have a protective effect by inhibiting extracellular matrix production and promoting wound repair in alveolar epithelial cells.

A new trend in sensitization to cockroach allergen: A cross-sectional study of indoor allergens and food allergens in the inland region of Southwest China.

BACKGROUND: Despite the increasing prevalence of allergic disease, large-scale studies to investigate allergen sensitization have rarely been conducted in the inland region of Southwest China. OBJECTIVE: This study aimed to investigate the trend of allergen sensitization in mainland China from 2016 to 2017. METHODS: During the 2-year study period, from 2016 to 2017, the serum samples of 7,759 allergic patients collected from 38 hospitals in Yunnan were detected the specific immunoglobulin E (sIgE) against 8 indoor and food allergens, namely, house dust mite, cockroach, dog dander, mold mix, egg white, milk, crab, and shrimp. The polysensitization patterns were analyzed through cluster analysis, and the relationship between cockroach and other indoor and food allergens was analyzed. RESULTS: Allergen sIgE positivity was prevalent in 45.6% of the population. Cockroach was the most common allergen (27.0%), followed by house dust mite (25.6%), shrimp (18.8%) and crab (15.6%). Three polysensitization clusters were identified: cluster 1): egg white/milk; cluster 2): crab/shrimp/cockroach/house dust mite/dog dander; and cluster 3): mold mix. The sIgE levels and sensitization rates to house dust mite, crab, and shrimp increased with the level of cockroach sIgE (P < 0.05). CONCLUSIONS: Based on big data in the real world, we found that there is a new trend in common allergens in Southwest China, where house dust mite is the only available reagent of specific immunotherapy. Cockroaches may become another major allergen in mainland China in the future, and clinicians should be aware of this.

ERC-BiP Functional Protein Pathway for Assessing Endoplasmic Reticulum Stress Induced by SARS-CoV-2 Replication after Cell Invasion.

Background: SARS-CoV-2 induces apoptosis and amplifies the immune response by continuously stressing the endoplasmic reticulum (ER) after invading cells. This study aimed to establish a protein-metabolic pathway associated with ER dysfunction based on the invasion mechanism of SARS-CoV-2. Methods: This study included 17 healthy people and 46 COVID-19 patients, including 38 mild patients and 8 severe patients. Proteomics and metabolomics were measured in the patient plasma collected at admission and one week after admission. The patients were further divided into the aggravation and remission groups based on disease progression within one week of admission. Results: Cross-sectional comparison showed that endoplasmic reticulum molecular chaperone-binding immunoglobulin protein (ERC-BiP), angiotensinogen (AGT), ceramide acid (Cer), and C-reactive protein (CRP) levels were significantly increased in COVID-19 patients, while the sphingomyelin (SM) level was significantly decreased (P < 0.05). In addition, longitudinal comparative analysis found that the temporal fold changes of ERC-BiP, AGT, Cer, CRP, and SM were significantly different between the patients in the aggravation and remission groups (P < 0.05). ERC-BiP, AGT, and Cer levels were significantly increased in aggravation patients, while SM was significantly decreased (P < 0.05). Meanwhile, ERC-BiP was significantly correlated with AGT (r = 0.439; P < 0.001). Conclusions: ERC-BiP can be used as a core index to reflect the degree of ER stress in COVID-19 patients, which is of great value for evaluating the functional state of cells. A functional pathway for AGT/ERC-BiP/glycolysis can directly assess the activation of unfolded protein reactions. The ERC-BiP pathway is closer to the intracellular replication pathway of SARS-CoV-2 and may help in the development of predictive protocols for COVID-19 exacerbation.

Immunoassay and mass cytometry revealed immunological profiles induced by inactivated BBIBP COVID-19 vaccine.

With the global prevalence of COVID-19 and the constant emergence of viral variants, boosters for COVID-19 vaccines to enhance antibody titers in human bodies will become an inevitable trend. However, there is a lack of data on antibody levels and the protective effects of booster injections. This study monitored and analyzed the antibody potency and the antibody responses induced by the booster injection in the subjects who received three vaccine doses. The study was conducted in a multicenter collaboration and recruited 360 healthy adults aged 20-74. Participants received the first, second, and booster doses of inactivated Sinopharm/BBIBP COVID-19 vaccine at 0, 1, and 7 months. Vaccine-induced virus-specific antibody levels (SARS-COV-2-IgA/IgM/IgG) were monitored at multiple time points, surrogate virus neutralization test (sVNT), and the spatial distribution and proportion of immune cells and markers were analyzed using the CyTOF method before vaccination and a month after the second dose. The titers of SARS-CoV-2-IgA/IgM/IgG and neutralizing antibodies increased to a high level in the first month after receiving the second dose of vaccine and declined slowly after that. The antibody levels of SARS-CoV-2-IgG and sVNT were significantly increased at 0.5 months after the induction of the booster (p < 0.05). Despite a downward trend, the antibody levels were still high in the following 6 months. The B cell concentration (in humoral sample) a month after the second injection was significantly reduced compared to that before the vaccine injection (p < 0.05). The proportion of the C01 cell cluster was significantly decreased compared with that before vaccine injection (p < 0.05). Individual cell surface markers showed distinctions in spatial distribution but were not significantly different. This study has shown that serum antibody titer levels will decrease with time by monitoring and analyzing the antibody efficacy and the antibody reaction caused by the booster injection of healthy people who received the whole vaccination (completed three injections). Still, the significant peak of the antibody titer levels after booster highlights the recall immune response. It can maintain a high concentration of antibody levels for a long time, which signifies that the protection ability has been enhanced following the injection of booster immunization. Additionally, CyTOF data shows the active production of antibodies and the change in the immunity environment.

Loss modulation assisted solitonic pulse excitation in Kerr resonators with normal group velocity dispersion.

We demonstrate an emergent solitonic pulse generation approach exploiting the externally introduced or intrinsic loss fluctuation effects. Single or multiple pulses are accessible via self-evolution of the system in the red, blue detuning regime or even on resonance with loss perturbation. The potential well caused by the loss profile not only traps the generated pulses, but also helps to suppress the drift regarding high-order dispersion. Breathing dynamics is also observed with high driving force, which can be transferred to stable state by backward tuning the pump detuning. We further investigate the intrinsic free carrier absorption, recognized as unfavored effect traditionally, could be an effective factor for pulse excitation through the time-variant loss fluctuation in normal dispersion microresonators. Pulse excitation dynamics associated with physical parameters are also discussed. These findings could establish a feasible path for stable localized structures and Kerr microcombs generation in potential platforms.

A synthesized olean-28,13ß-lactam targets YTHDF1-GLS1 axis to induce ROS-dependent metabolic crisis and cell death in pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a severe malignant with a 5-year survival rate of approximately 9%. Oleanolic acid is a well-known natural triterpenoid which exhibits pharmacological activities. We previously synthesized a series of oleanolic acid derivatives and evaluated the tumor-suppressive activity of olean-28,13ß-lactam (B28) in prostate cancer. However, the detailed mechanism remains to be understood. METHODS: The anti-tumor activity of B28 in PAAD was confirmed by RTCA, colony formation assay and flow cytometry. GO and KEGG enrichment analyses were performed to analyze the differentially expressed genes (DEGs) obtained by RNA sequencing. The effects of B28 on cell bioenergetics were evaluated by seahorse analyzer. Lenti-virus packaged plasmids were performed to knockdown or overexpress target genes. Alteration of mitochondrial membrane potential, ROS and GSH/GSSG were measured by corresponding detection kits according to the manufacturer's protocol. RESULTS: We evaluated and confirmed the promising anti-tumor activity of B28 in vitro. RNA-seq profile indicated that multiple metabolic pathways were interrupted in B28 treated PAAD cells. Next, we demonstrated that B28 induces cellular bioenergetics crisis to inhibit PAAD cells growth and induce cell death. We further validated that cell cycle arrest, inhibition of cell growth, cell apoptosis and cell bioenergetics disruption were functionally rescued by ROS scavenger NAC. Mechanistically, we found glutamine metabolism was inhibited due to B28 administration. Moreover, we validated that down-regulation of GLS1 contributes to ROS generation and bioenergetics interruption induced by B28. Furthermore, we elucidated that YTHDF1-GLS1 axis is the potential downstream target of B28 to induce PAAD cell metabolic crisis and cell death. Finally, we also confirmed the anti-tumor activity of B28 in vivo. CONCLUSIONS: Current study demonstrates B28 disrupts YTDFH1-GLS1 axis to induce ROS-dependent cell bioenergetics crisis and cell death which finally suppress PAAD cell growth, indicating that this synthesized olean-28,13ß-lactam maybe a potent agent for PAAD intervention.

Humoral immune response of BBIBP COVID-19 vaccination before and after the booster immunization.

BACKGROUND: The inactivated Sinopharm/BBIBP COVID-19 vaccine has been widely used in the world and has joined the COVAX vaccine supply program for developing countries. It is also well adapted for usage in low- and middle-income nations due to their low storage requirements. OBJECTIVE: This study aims to report on the kinetics, durability, and neutralizing ability of the induced immunity of the BBIBP vaccine, and the intensified antibody response elicited by the booster. METHODS: A total of 353 healthy adult participants, aged 20-74 years, were recruited in this multicenter study. A standard dose of the BBIBP vaccine was administered (Month 0), followed by a second standard dose (Month 1), and a booster dose (after Month 7). Vaccine-induced virus-specific antibody levels (SARS-CoV-2-IgA/IgM/IgG), conventional virus neutralization test (cVNT), pseudovirus neutralization test (pVNT), and surrogate virus neutralization test (sVNT) were monitored over multiple time points. RESULTS: Neutralizing titers induced by the two doses of inactivated vaccine for COVID-19 peaked at Month 2 and declined to 33.89% at Month 6. Following the booster dose, elevated levels of antibodies were induced for IgA, IgG, and neutralizing antibodies, with neutralizing titer reaching 13.2 times that of before the booster. CONCLUSION: By monitoring the antibody titer levels postvaccination, this study has shown that serum antibody levels will decrease over time, but a notable spike in antibody levels postbooster highlights the anamnestic immune response. This signifies that the protection capability has increased following the injection of booster immunization.