The disease burden of bladder cancer and its attributable risk factors in five Eastern Asian countries, 1990-2019: a population-based comparative study.

BACKGROUNDS: The study aimed to estimate bladder cancer burden and its attributable risk factors in China, Japan, South Korea, North Korea and Mongolia from 1990 to 2019, to discuss the potential causes of the disparities. METHODS: Data were obtained from the Global Burden of Disease Study 2019. The annual percent change (APC) and average annual percent change (AAPC) were calculated by Joinpoint analysis, and the independent age, period and cohort effects were estimated by age-period-cohort analysis. RESULTS: In 2019, the highest incidence (7.70 per 100,000) and prevalence (51.09 per 100,000) rates of bladder cancer were in Japan, while the highest mortality (2.31 per 100,000) and DALY rates (41.88 per 100,000) were in South Korea and China, respectively. From 1990 to 2019, the age-standardized incidence and prevalence rates increased in China, Japan and South Korea (AAPC > 0) and decreased in Mongolia (AAPC < 0), while mortality and DALY rates decreased in all five countries (AAPC < 0). Age effects showed increasing trends for incidence, mortality and DALY rates, while the prevalence rates increased first and then decreased in older groups. The cohort effects showed downward trends from 1914-1918 to 2004-2008. Smoking was the greatest contributor and males had the higher burden than females. CONCLUSION: Bladder cancer was still a major public health problem in East Asia. Male and older population suffered from higher risk, and smoking played an important role. It is recommended that more efficient preventions and interventions should be operated among high-risk populations, thereby reduce bladder cancer burden in East Asia.

Does Internet use improve the physical and mental health of older adults in China? A study based on the digital divide theory.

In the digital era, increasingly more Chinese older adults have become Internet users, but the digital divide deeply affects their health. Based on the China Longitudinal Aging Social Survey, the influence of Internet use on older adults' physical and mental health are examined. It is found that digital access, online socializing and information/knowledge acquisition improve older adults' physical and mental health, while Internet skills can hardly influence their health. Social connection and adaptation are two important channels through which Internet use improves older adults' health. Younger and better-educated older adults gain more health benefits from Internet access, but online socializing and economic activities show stronger positive health effects in less-educated older adults. Narrowing the digital divide and promoting digital cohesion are important for the health of older population, so the health and pensions sector and geriatric nursing providers should help this group integrate into digital life to improve their health.

Bifurcation detection in intravascular optical coherence tomography using vision transformer based deep learning.

Objective. Bifurcation detection in intravascular optical coherence tomography (IVOCT) images plays a significant role in guiding optimal revascularization strategies for percutaneous coronary intervention (PCI). We propose a bifurcation detection method using vision transformer (ViT) based deep learning in IVOCT.Approach. Instead of relying on lumen segmentation, the proposed method identifies the bifurcation image using a ViT-based classification model and then estimate bifurcation ostium points by a ViT-based landmark detection model.Main results. By processing 8640 clinical images, the Accuracy and F1-score of bifurcation identification by the proposed ViT-based model are 2.54% and 16.08% higher than that of traditional non-deep learning methods, are similar to the best performance of convolutional neural networks (CNNs) based methods, respectively. The ostium distance error of the ViT-based model is 0.305 mm, which is reduced 68.5% compared with the traditional non-deep learning method and reduced 24.81% compared with the best performance of CNNs based methods. The results also show that the proposed ViT-based method achieves the highest success detection rate are 11.3% and 29.2% higher than the non-deep learning method, and 4.6% and 2.5% higher than the best performance of CNNs based methods when the distance section is 0.1 and 0.2 mm, respectively.Significance. The proposed ViT-based method enhances the performance of bifurcation detection of IVOCT images, which maintains a high correlation and consistency between the automatic detection results and the expert manual results. It is of great significance in guiding the selection of PCI treatment strategies.

Multi-omics analysis reveals that Cas13d contributes to PI3K-AKT signaling and facilitates cell proliferation via PFKFB4 upregulation.

The CRISPR-Cas system is a powerful gene editing technology, the clinical application of which is currently constrained due to safety concerns. A substantial body of safety research concerning Cas9 exists; however, scant attention has been directed toward investigating the safety profile of the emergent Cas13 system, which confers RNA editing capabilities. In particular, uncertainties persist regarding the potential cellular impacts of Cas13d in the absence of reliance on a cleavage effect. In this study, we conducted an initial exploration of the effects of Cas13d on HeLa cells. Total RNA and protein samples were extracted after transfection with a Cas13d-expressing plasmid construct, followed by transcriptomic and proteomic sequencing. Differential gene expression analysis identified 94 upregulated and 847 downregulated genes, while differential protein expression analysis identified 185 upregulated and 231 downregulated proteins. Subsequently, enrichment analysis was conducted on the transcriptome and proteome sequencing data, revealing that the PI3K-Akt signaling pathway is a common term. After intersecting the differentially expressed genes enriched in the PI3K-Akt signaling pathway with all the differentially expressed proteins, it was found that the expression of the related regulatory gene PFKFB4 was upregulated. Moreover, western blot analysis demonstrated that Cas13d can mediate PI3K-Akt signaling upregulation through overexpression of PFKFB4. CCK-8 assay, colony formation, and EdU experiments showed that Cas13d can promote cell proliferation. Our data demonstrate, for the first time, that Cas13d significantly impacts the transcriptomic and proteomic profiles, and proliferation phenotype, of HeLa cells, thus offering novel insights into safety considerations regarding gene editing systems.

Step-adaptive accelerated demodulation algorithm for LFM-pulse-based distributed acoustic sensing.

We propose a novel, to our knowledge, step-adaptive cross-correlation algorithm tailored for distributed acoustic sensing systems based on linear frequency modulation pulses, aiming for rapid demodulation. This algorithm adjusts its step length through an adaptive "successive refinement" search strategy, which greatly improves computational efficiency by reducing the number of cross-correlation computations. Experimental results have shown that the demodulation time can be reduced by approximately 15 times compared to the conventional method, while maintaining the same demodulation result.

The Highly Sensitive Refractive Index Sensing of Seawater Based on a Large Lateral Offset Mach-Zehnder Interferometer.

A novel fiber sensor for the refractive index sensing of seawater based on a Mach-Zehnder interferometer has been demonstrated. The sensor consisted of a single-mode fiber (SMF)-no-core fiber (NCF)-single-mode fiber structure (shortened to an SNS structure) with a large lateral offset spliced between the two sections of a multimode fiber (MMF). Optimization studies of the multimode fiber length, offset SNS length, and vertical axial offset distance were performed to improve the coupling efficiency of interference light and achieve the best extinction ratio. In the experiment, a large lateral offset sensor was prepared to detect the refractive index of various ratios of saltwater, which were used to simulate seawater environments. The sensor's sensitivity was up to -13,703.63 nm/RIU and -13,160 nm/RIU in the refractive index range of 1.3370 to 1.3410 based on the shift of the interference spectrum. Moreover, the sensor showed a good linear response and high stability, with an RSD of only 0.0089% for the trough of the interference in air over 1 h.

Genome-Wide Identification of Expansins in Rubus chingii and Profiling Analysis during Fruit Ripening and Softening.

Improving fruit size or weight, firmness, and shelf life is a major target for horticultural crop breeding. It is associated with the depolymerization and rearrangement of cell components, including pectin, hemicellulose, cellulose, and other structural (glyco)proteins. Expansins are structural proteins to loosen plant cell wall polysaccharides in a pH-dependent manner and play pivotal roles in the process of fruit development, ripening, and softening. Rubus chingii Hu, a unique Chinese red raspberry, is a prestigious pharmaceutical and nutraceutical dual-function food with great economic value. Thirty-three RchEXPs were predicted by genome-wide identification in this study, containing twenty-seven α-expansins (EXPAs), three ß-expansins (EXPBs), one expansin-like A (EXPLA), and two expansin-like B (EXPLBs). Subsequently, molecular characteristics, gene structure and motif compositions, phylogenetic relationships, chromosomal location, collinearity, and regulatory elements were further profiled. Furthermore, transcriptome sequencing (RNA-seq) and real-time quantitative PCR assays of fruits from different developmental stages and lineages showed that the group of RchEXPA5, RchEXPA7, and RchEXPA15 were synergistically involved in fruit expanding and ripening, while another group of RchEXPA6 and RchEXPA26 might be essential for fruit ripening and softening. They were regulated by both abscisic acid and ethylene and were collinear with phylogenetic relationships in the same group. Our new findings laid the molecular foundation for improving the fruit texture and shelf life of R. chingii medicinal and edible fruit.

Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast.

CO2 fixation plays a key role to make biobased production cost competitive. Here, we use 3-hydroxypropionic acid (3-HP) to showcase how CO2 fixation enables approaching theoretical-yield production. Using genome-scale metabolic models to calculate the production envelope, we demonstrate that the provision of bicarbonate, formed from CO2, restricts previous attempts for high yield production of 3-HP. We thus develop multiple strategies for bicarbonate uptake, including the identification of Sul1 as a potential bicarbonate transporter, domain swapping of malonyl-CoA reductase, identification of Esbp6 as a potential 3-HP exporter, and deletion of Uga1 to prevent 3-HP degradation. The combined rational engineering increases 3-HP production from 0.14 g/L to 11.25 g/L in shake flask using 20 g/L glucose, approaching the maximum theoretical yield with concurrent biomass formation. The engineered yeast forms the basis for commercialization of bio-acrylic acid, while our CO2 fixation strategies pave the way for CO2 being used as the sole carbon source.

When does a freemium business model lead to high performance? - A qualitative comparative analysis based on fuzzy Sets.

Existing research has neglected to explain why freemium business models lead to differentiated performance or what accounts for the difference in their revenue models. This study investigates how the configuration effect of freemium business models promotes performance and explores the different ways through which freemium business models, their dynamic capabilities, and environmental uncertainty interact to achieve high performance. The fuzzy set qualitative comparative analysis (fsQCA) approach was used to test the conceptual model with data from 45 freemium business model apps. From empirical evidence on the relationship between freemium business models, dynamic capabilities, and environmental uncertainty, the study finds that (1) bundled and fragmented freemium business models are fundamental performance drivers. However, they work only in combination with dynamic capabilities and environmental uncertainty. Moreover, the bundled and fragmented freemium business models have complementary rather than substitution relationships. (2) For companies with bundled and fragmented freemium business models, high sensing and seizing capabilities are critical to achieving high performance. A high bundled freemium business model, high sensing capability, and a lack of fragmented freemium business models and seizing capability can lead to high performance, regardless of reconfiguration capabilities and environmental uncertainty. (3) Under high environmental uncertainty, offering fragmented freemium business models with or without a bundled freemium business model will lead to high performance if they have high sensing, seizing, and reconfiguring capabilities. This study can provide systematic decision support for achieving high performance through freemium business models and the configuration of dynamic capabilities under environmental uncertainty.

Modeling of human muscle and its deformation.

There is a lack of volume preserving and reasonable deformation of human muscles during bones and joints movement in the field of digital orthopedics. A novel approach for modeling of human muscle and its deformation was put forward to effectively assist doctors in guiding patients to carry out rehabilitation exercises. Firstly, based on Magnetic Resonance Imaging (MRI) data, the generated slice images were used to extract the outer contour lines and then the corresponding contour lines and optimal matching points of the adjacent layer images were connected to construct the three-dimensional (3D) geometric models of the muscles; Secondly, the mapping relationship between parameters can be established through hierarchical definition of the muscle characteristics to realize the volume-preserving deformation of muscle; Finally, the movement of human joints can be realized based on the constraint range of joint movement, and the vector-valued dynamic fourth-order differential equation was proposed to make the characteristic curve dynamically simulate the process of muscle deformation, thereby forming the corresponding relationship between bone movement and muscle deformation. The effectiveness and feasibility of this method have been verified in our experiments with biceps brachii and triceps brachii as examples. The maximum volume errors of biceps brachii and triceps brachii during the deformation process were less than 0.6%, which can be ignored within a certain allowable error range, reflecting that the parametric method was used to realize the reasonable volume-preserving deformation of human muscle.

Hollow-microsphere-integrated optofluidic immunochip for myocardial infarction biomarker microanalysis.

This work developed an optofluidic immunochip that uses whispering gallery mode with fiber laser enhancement, for the rapid detection of a key biomarker cardiac troponin I for acute myocardial infarction (AMI). The immunochip adopted an innovative design, using perforated hollow glass microspheres (HGMS) as carriers, with antibodies immobilized on the inner surface of the HGMS, thereby achieving ultra-low sample consumption. The performance of the immunochip was improved by fiber laser, including spectral width compression to 0.019 nm, optical signal-to-noise ratio amplification to 63.17 dB, and an enhancement in the limit of detection to 5 pg/mL. Moreover, this immunochip can provide results within 15 min, making it highly suitable for early AMI risk management. Compared to the standard electrochemiluminescence detection method, although some differences exist in the results of the immunochip due to the principle of detection and differences in antibody affinity, its positive reference value can be calculated as 0.0754 ng/mL, with a successful recognition rate of 88% for positive patients. The immunosensor is integrated on a polydimethylsiloxane substrate, with a compact size suitable for use in point-of-care devices and AMI self-screening, as well as rapid disease screening and microanalysis of various biomarkers, offering new possibilities for applications in these fields.

Simultaneous bond-selective deuterium-based isotopic labeling sensing with disposable ultra-miniature CARS fiber probe.

Deuterium-based isotopic labeling is an important technique for tracking cellular metabolism with the Raman signals analysis of low-wavenumber (LW) C-D bonds and high-wavenumber (HW) C-H bonds. We propose and demonstrate a disposable ultra-miniature fiber probe to detect LW and HW coherent anti-Stokes Raman scattering (CARS) spectra for deuterated compounds simultaneously and bond-selectively sensing. The 10.78 µm diameter disposable fiber probe, comprised of focusing taper as fiber probe head and time-domain walk-off eliminating fiber section with designed length, realizes wide-frequency-interval dual Stokes pulse delivering and focusing. The fiber probe enables quantitative concentration determination with resolution down to 11 mM. The chemical vibration modes of LW region C-D bonds and HW region C-H bonds of the mixture samples of organic compounds and their deuterated counterparts in a simulated cell are simultaneously excited and characterized. The CARS disposable fiber probe introduces a promising handle for in vivo biochemical detection based on isotopic labeling sensing.

Longitudinal evaluation of innate immune responses to three doses of CoronaVac vaccine.

The adaptive immune responses induced by inactivated COVID-19 vaccine has been extensively studied. However, few studies have analyzed the impact of COVID-19 vaccination on innate immune cells. Here in this study, we recruited 62 healthcare workers who received three doses of CoronaVac vaccine and longitudinally profiled the alterations of peripheral monocytes and NK cells during vaccination. The results showed that both the monocyte and NK cell subsets distribution were altered, although the frequencies of the total monocyte and NK cells remained stable during the vaccination. Additionally, we found that both the 2nd and 3rd dose of CoronaVac vaccination elicited robust IFN-γ-producing NK cell response. Our data provided necessary insights on innate immune responses in the context of three homologous CoronaVac dose vaccination, and supplied immunological basis for the future design of inactivated vaccines against SARS-CoV-2 or other viruses.

High sensitivity composite F-P cavity fiber optic sensor based on MEMS for temperature and salinity measurement of seawater.

We proposed an optical fiber salinity sensor with a composite Fabry-Perot (F-P) cavity structure for simultaneous measurement of temperature and salinity based on microelectromechanical system (MEMS) technology. The sensor contains two sensing cavities. The silicon cavity is used for temperature sensing, and the seawater cavity processed by the glass microstructure is sensitive to the refractive index of seawater for salinity sensing. At the same time, the influence of the salinity-temperature cross-sensitivity error of the seawater cavity is effectively compensated by using the temperature single parameter sensitivity characteristics of the silicon cavity. The structural design of the sensor seawater cavity includes a cross-shaped groove and a cylindrical fluid cavity. The surface hydrophilicity treatment was performed on the interior of the cavity to solve the effect of no water injection in the cavity caused by the miniaturization of the sensor. The optical path difference (OPD) demodulation method is used to demodulate the two F-P cavities with large dynamic range and high resolution. In the range of 5∼40°C and 5∼ 40 ‰, the temperature and salinity sensitivity of the sensor can reach 110.25 nm/°C and 178.75 nm/‰, respectively, and the resolution can reach 5.02 × 10-3°C and 0.0138‰. It has the advantages of mass production, high stability, and small size, which give it great potential for marine applications.

Neutralizing activity of a third dose of CoronaVac against Omicron subvariants within a 20-month follow-up study.

The durability of antibody responses induced by the three-dose of CoronaVac vaccination, especially against SARS-CoV-2 Omicron subvariants, remains unclear. Here in our study, 160 plasma samples from 32 healthy individuals who received three doses of CoronaVac were longitudinally tracked for a period of 20 months. The results showed that a third homologous dose of CoronaVac efficiently increased the SARS-CoV-2 IgG and neutralizing antibody titers and enhanced neutralization activity against Omicron subvariants. The levels of IgG and neutralizing antibody declined from peak levels but remained detectable in most subjects over the course of the next 10-12 months. However, most of the individuals kept neutralizing titers against ancestral Wuhan-Hu-1, while they lost their neutralizing activities against Omicron B.1.1.529, BA.2, BA.4/BA.5, and BA.2.75.2 subvariants at 10-12 months post the third vaccination. Our results suggest that a fourth dose of vaccine may be necessary for uninfected individuals to confer higher neutralization against emerging Omicron subvariants.

Highly sensitive and label-free detection of biotin using a liquid crystal-based optofluidic biosensor.

A liquid crystal (LC)-based optofluidic whispering gallery mode (WGM) resonator has been applied as a biosensor to detect biotin. Immobilized streptavidin (SA) act as protein molecules and specifically bind to biotin through strong non-covalent interaction, which can interfere with the orientation of LCs by decreasing the vertical anchoring force of the alignment layer in which the WGM spectral wavelength shift is monitored as a sensing parameter. Due to the double magnification of the LC molecular orientation transition and the resonance of the WGM, the detection limit for SA can reach 1.25 fM (4.7 × 10-13 g/ml). The measurable concentration of biotin and the wavelength shift of the WGM spectrum have an excellent linearity in the range of 0 to 0.1 pg/ml, which can achieve ultra-low detection limit (0.4 fM), i.e., seven orders of magnitude improvement over conventional polarized optical microscope (POM) method. The proposed optofluidic biosensor is highly reproducible and can be used as an ultrasensitive real-time monitoring biosensor, which will open the door for applications to other receptor and ligand models.

Longitudinal analysis of memory Tfh cells and antibody response following CoronaVac vaccination.

The inactivated vaccine CoronaVac is one of the most widely used COVID-19 vaccines globally. However, the longitudinal evolution of the immune response induced by CoronaVac remains elusive compared with other vaccine platforms. Here, we recruited 88 healthy individuals who received 3 doses of CoronaVac vaccine. We longitudinally evaluated their polyclonal and antigen-specific CD4+ T cells and neutralizing antibody response after receiving each dose of vaccine for over 300 days. Both the second and third doses of vaccine induced robust spike-specific neutralizing antibodies, with a third vaccine further increasing the overall magnitude of antibody response and neutralization against Omicron sublineages B.1.1.529, BA.2, BA.4/BA.5, and BA.2.75.2. Spike-specific CD4+ T cells and circulating T follicular helper (cTfh) cells were markedly increased by the second and third dose of CoronaVac vaccine, accompanied by altered composition of functional cTfh cell subsets with distinct effector and memory potential. Additionally, cTfh cells were positively correlated with neutralizing antibody titers. Our results suggest that CoronaVac vaccine-induced spike-specific T cells are capable of supporting humoral immunity for long-term immune protection.

Cometabolic degradation of pyrene with phenanthrene as substrate: assisted by halophilic Pseudomonas stutzeri DJP1.

At present, cometabolic degradation is an extensive method for the biological removal of high molecular weight polycyclic aromatic hydrocarbons (HMW-PAHs) in the marine environment. However, due to the refractory to degradation and high toxicity, there are few studies on pyrene (PYR) cometabolic degradation with phenanthrene (PHE) as substrate. In this study, a Pseudomonas stutzeri DJP1 strain isolated from sediments was used in the cometabolic system of PHE and PYR. The biomass and the activity of key enzymes such as dehydrogenase and catechol 12 dioxygenase of strain were improved, but the enhancement of biotoxicity resulted in the inhibition of cometabolism simultaneously. Seven metabolites were identified respectively in PYR, PHE degradation cultures. It was speculated that the cometabolism of PHE and PYR had a common phthalic acid pathway, and the degradation pathway of PHE was included in the downstream pathway of PYR. The functional genes such as PhdF, NidD and CatA involved in DJP1 degradation were revealed by Genome analysis. This study provides a reference for the biodegradation of PYR and PHE in real marine environment.

A study combining a sediment-seawater microcosm with multimedia fugacity model to evaluate the effect of tidal cycles on polycyclic aromatic hydrocarbon release from sediments.

Estuarine sediments are key storage sites for persistent organic pollutants (POPs), and estuaries are strongly influenced by tides throughout the year. Although much work has been done concerning on POPs release, related questions on tidal action have not been considered in the release process. Herein, polycyclic aromatic hydrocarbons (PAHs) release from sediment to seawater was investigated under tidal action by combining a tidal microcosm with level IV fugacity model. The results showed that PAHs release with tidal action was 2.0-3.5 times the accumulation of that without tidal action. Tidal action was confirmed to influence strongly PAHs release from sediment to seawater. We also quantified suspended substance (SS) in the overlying water, and an obvious positive correlation between the PAHs concentration and SS content was found. In addition, an increase in seawater depth enhanced the intensity of tidal action, and more PAHs were released, especially dissolved PAHs. Moreover, the fugacity model results showed a good fit with the experimental results. The simulated values demonstrated that the PAHs release was accomplished via two processes, "rapid release" and "slow release". And the sediment played a key role in the fate of PAHs and was a major sink in the sediment-seawater system.

Ascending aorta dilatation reduces the influence of elevated pulse pressure on left ventricular hypertrophy: findings from a Chinese elderly hypertensive population.

OBJECTIVE: To determine the role of ascending aorta dilatation in the relationship between pulse pressure (PP) and left ventricular (LV) hypertrophy. METHODS: A total of 1556 Chinese elderly hypertensive patients were retrospectively studied. Transthoracic echocardiography was used to obtain the aortic and cardiac structure measurements. In addition, brachial blood pressure was measured, and total arterial compliance, systemic vascular resistance, arterial elastance, and end-systolic LV elastance were calculated. The participants were divided into four groups according to the status of ascending aortic diameter and PP. RESULTS: LV mass index increased in succession in the four groups, i.e., the group with the normal aorta and lower PP, with the normal aorta and higher PP, with aortic dilatation and lower PP, and with aortic dilatation and higher PP (P trend < 0.001). Total arterial compliance-1, arterial elastance, and end-systolic LV elastance were slightly higher in the individuals with normal aorta compared to those with aortic dilatation, regardless of PP being lower or higher (P < 0.01). Compared to the group with the normal aorta and lower PP, individuals with aortic dilatation had a significantly increased multivariable adjusted risk of LV hypertrophy, and higher PP further exacerbated this risk [aortic dilatation with lower PP (OR = 1.75, 95% CI: 1.01-3.04) and aortic dilatation with higher PP (OR = 3.42, 95% CI: 2.03-5.77)]. In the relation between PP and LV mass index (ß = 0.095, P < 0.001), -41.3% of the total effect was attributable to mediation by ascending aortic diameter (P < 0.0001). CONCLUSIONS: In Chinese elderly patients with hypertension, ascending aorta dilatation could reduce the influence of elevated PP on LV hypertrophy.