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Calcium ion (Ca2+) cycle plays a crucial role in the contraction and relaxation of cardiomyocytes. The sarcoplasmic reticulum (SR) acts as an organelle for storing Ca2+, which mediated the release and re-uptake of Ca2+ during contraction and relaxation. Disorders of SR function lead to the dysfunction of Ca2+ cycle and myocardial cell function. The sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) acts as a subtype of SERCA expressed in the heart, which mediates the contraction of cardiomyocytes and Ca2+ in the cytoplasm to re-enter into the SR. The rate of uptake of Ca2+ by the SR determines the rate of myocardial relaxation. The regulation of SERCA2a activity controls the contractility and relaxation of the heart, affecting cardiac function. The expression and activity of SERCA2a are reduced in failing hearts. Gene therapy by increasing the expression of SERCA2a in the heart has been proven effective. In addition, SERCA2a is regulated by a variety of factors, including transmembrane micropeptides, protein kinases, and post-translational modifications (PTMs). In this review, we discuss the regulatory factors of SERCA2a and provide new insights into future treatments and the direction of heart failure research. In addition, gene therapy for SERCA2a has recently emerged as therapeutic option and hence will be discussed in this review.

Monitoring grassland productivity dynamics is essential for understanding the impacts of climate variation and human activities. Solar-induced chlorophyll fluorescence (SIF) has been validated as an effective indicator of gross primary productivity. Satellite-derived vegetation indices (VIs) have long been used as key proxies for vegetation productivity. However, the ability of different VIs to represent grassland productivity in relation to SIF, as well as their spatiotemporal consistency with SIF at various scales, remains unclear. In this study, we systematically compared the performance of the Normalized Difference Vegetation Index (NDVI), the Enhanced Vegetation Index (EVI), and the Near-Infrared Reflectance of Vegetation (NIRv), using SIF as a benchmark in grassland areas of China. Utilizing TROPOMI SIF and MODIS VI datasets from 2018 to 2021, we analyzed the spatial and temporal consistency between VIs and SIF at a monthly scale and 0.05-degree resolution, employing Pearson correlation coefficients, paired-sample t-tests, and two-way Analysis of Variance (ANOVA). The results indicate that NIRv consistently demonstrates a higher capacity to capture variations in SIF compared to EVI and NDVI. In low-elevation areas with high-productivity grasslands, all three vegetation indices exhibit a stronger ability to represent vegetation productivity than in high-elevation areas with low-productivity vegetation types. These findings suggest that, at a monthly and regional spatiotemporal scale, NIRv can serve as a robust complement to SIF in monitoring vegetation productivity dynamics, particularly given the challenges in acquiring high-quality, long-term SIF data.

The CCL2-CCR2 axis is one of the major chemokine signaling pathways that has received special attention because of its function in the development and progression of cardiovascular disease. Numerous investigations have been performed over the past decades to explore the function of the CCL2-CCR2 signaling axis in cardiovascular disease. Laboratory data on the CCL2-CCR2 axis for cardiovascular disease have shown satisfactory outcomes, yet its clinical translation remains challenging. In this article, we describe the mechanisms of action of the CCL2-CCR2 axis in the development and evolution of cardiovascular diseases including heart failure, atherosclerosis and coronary atherosclerotic heart disease, hypertension and myocardial disease. Laboratory and clinical data on the use of the CCL2-CCR2 pathway as a targeted therapy for cardiovascular diseases are summarized. The potential of the CCL2-CCR2 axis in the treatment of cardiovascular diseases is explored.

Salvia miltiorrhiza: (Danshen) is a significant (traditional Chinese medication) natural remedy, enhancing blood circulation and clear blood stasis. In this view, it is widely used against several heart diseases, eg, cardiomyopathy, arrhythmia, and congenital heart defects. Tanshinone IIA (tan-IIA) is the main fat-soluble component of Salvia miltiorrhiza. Modern pharmacological study shows that tan-IIA has anti-inflammatory and anti-oxidant activities. Tan-IIA induces remarkable cardioprotective effects via enhancing angiogenesis which may serve as an effective treatment against cardiovascular diseases (CVD). There is also evidence that tan-IIA has extensive immunomodulatory effects and plays a significant role in the development and function of immune cells. Tan-IIA reduces the production of inflammatory mediators and restores abnormal signaling pathways via regulating the function and activation of immune cells. It can also regulate signal transduction pathways, ie, TLR/NF-[kappa]B pathway and MAPKs/NF-[kappa]B pathway, thereby tan-IIA has an anti-inflammatory, anticoagulant, antithrombotic and neuroprotective role. It plays a protective role in the pathogenesis of cardiovascular disorders (ie, atherosclerosis, hypertension) and Alzheimer's disease. It has also been revealed that tan-IIA has an anti-tumor role by killing various tumor cells, inducing differentiation and apoptosis, and has potential activity against carcinoma progression. In the review of this fact, the tan-IIA role in different diseases and its mechanism have been summarized while its clinical applications are also explored to provide a new perspective of Salvia miltiorrhiza. An extensive study on the mechanism of action of tan-IIA is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world. Keywords: tanshinone-IIA, atherosclerosis, Alzheimer' disease, cancer, anti-inflammation, anti-oxidative

Upland cotton is the most important natural-fiber crop. The genomic variation of diverse germplasms and alleles underpinning fiber quality and yield should be extensively explored. Here, we resequenced a core collection comprising 419 accessions with 6.55-fold coverage depth and identified approximately 3.66 million SNPs for evaluating the genomic variation. We performed phenotyping across 12 environments and conducted genome-wide association study of 13 fiber-related traits. 7,383 unique SNPs were significantly associated with these traits and were located within or near 4,820 genes; more associated loci were detected for fiber quality than fiber yield, and more fiber genes were detected in the D than the A subgenome. Several previously undescribed causal genes for days to flowering, fiber length, and fiber strength were identified. Phenotypic selection for these traits increased the frequency of elite alleles during domestication and breeding. These results provide targets for molecular selection and genetic manipulation in cotton improvement. The authors resequence a core collection of upland cotton ( Gossypium hirsutum ) comprising 419 accessions. They analyze genomic variation and conduct a genome-wide association study for 13 fiber quality and yield traits in 12 different environments.

Automatic detection of kiwifruit in the orchard is challenging because illumination varies through the day and night and because of color similarity between kiwifruit and the complex background of leaves, branches and stems. Also, kiwifruits grow in clusters, which may result in having occluded and touching fruits. A fast and accurate object detection algorithm was developed to automatically detect kiwifruits in the orchard by improving the YOLOv3-tiny model. Based on the characteristics of kiwifruit images, two convolutional kernels of 3 × 3 and 1 × 1 were added to the fifth and sixth convolution layers of the YOLOv3-tiny model, respectively, to develop a deep YOLOv3-tiny (DY3TNet) model. It takes multiple 1 × 1 convolutional layers in intermediate layers of the network to reduce the computational complexity. Testing images captured from day and night and comparing with other deep learning models, namely, Faster R-CNN with ZFNet, Faster R-CNN with VGG16, YOLOv2 and YOLOv3-tiny, the DY3TNet model achieved the highest average precision of 0.9005 with the smallest data weight of 27 MB. Furthermore, it took only 34 ms on average to process an image of a resolution of 2352 × 1568 pixels. The DY3TNet model, along with the YOLOv3-tiny model, showed better performance on images captured with flash than those without. Moreover, the experiments indicated that the image augmentation process could improve the detection performance, and a simple lighting arrangement could improve the success rate of detection in the orchard. The experimental results demonstrated that the improved DY3TNet model is small and efficient and that it would increase the applicability of real-time kiwifruit detection in the orchard even when small hardware devices are used.

Background Given a prolonged course of Cervical spondylosis (CS) could cause irreversible neurological deficits, it is crucial to disseminate CS-related health information to the public to promote early diagnosis and treatment. YouTube has been widely used to search for medical information. However, the reliability and quality of videos on YouTube vary greatly. Thus, this study aimed to assess the reliability and educational quality of YouTube videos concerning CS and further explore strategies for optimization of patient education. Methods We searched YouTube online library for the keywords “cervical spondylosis”, “cervical radiculopathy” and “cervical myelopathy” on January 15, 2023. Ranked by “relevance”, the first 50 videos of each string were recorded. After exclusions, a total of 108 videos were included. All videos were extracted for characteristics and classified based on different sources or contents. Two raters independently evaluated the videos using Journal of American Medical Association (JAMA) benchmark criteria, Modified DISCERN (mDISCERN) tool, Global Quality Scale (GQS) and Cervical-Spondylosis-Specific Scale (CSSS), followed by statistical analyses. All continuous data were described as median (interquartile range). Results All videos had median values for JAMA, mDISCERN, GQS and CSSS scores of were 3.00 (1.00), 3.00 (2.00), 2.00 (1.00) and 7.00 (8.88), respectively. There were significant differences in VPI ( P  = 0.009) and JAMA ( P  = 0.001), mDISCERN ( P  < 0.001), GQS ( P  < 0.001) and CSSS ( P  < 0.001) scores among different sources. Videos from academic source had advantages in reliability and quality scores than other sources. VPI ( P  < 0.001), mDISCERN ( P  = 0.001), GQS ( P  < 0.001) and CSSS ( P  = 0.001) scores also significantly differed among videos of various contents. Spearman correlation analysis indicated VPI was not correlated with either reliability or quality. Multiple linear regression analysis showed a longer duration and an academic source were independent predictors of higher reliability and quality, while a clinical source also led to the higher video quality. Conclusions The reliability and educational quality of current CS-related videos on YouTube are unsatisfactory. Users face a high risk of encountering inaccurate and misleading information when searching for CS on YouTube. Longer duration, source of academic or clinician were closely correlated to higher video reliability and quality. Improving the holistic reliability and quality of online information requires the concerted effort from multiple parties, including uploaders, the platform and viewers.

Background Atherogenic index of plasma (AIP) has been reported as a critical predictor on the risks and clinical outcomes of cardiovascular diseases (CVDs), and we aimed to explore the potential predictive value of cumulative AIP on major adverse cardiac events (MACE), stroke, myocardial infarction (MI) and cardiovascular mortality. Methods A large-scale community-based prospective cohort was established from December 2011 to April 2012 and followed up in May to July 2014. The endpoint outcomes were obtained before December 31, 2021. AIP was calculated as the logarithmically transformed ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-c) and cumulative AIP was the average value of AIP in 2012 and 2014. Results An overall of 3820 participants (36.1% male) with mean (SD) age of 59.1 (8.7) years, were enrolled. Within a median follow-up of 7.5 years, a total of 371 (9.7%) participants were documented with MACE, 293 (7.7%) participants developed stroke, 68 (1.8%) suffered from MI and 65 (1.7%) experienced cardiovascular mortality. Multivariable Cox regression analysis revealed significant associations between cumulative AIP and the risk of MACE, stroke and MI. Regarding MACE, individuals with one higher unit of cumulative AIP were associated with 75% increment on the incidence of going through MACE in fully adjusted model, while categorizing participants into four groups, individuals in the highest cumulative AIP quartile were significantly associated with increased incidence of MACE (HR = 1.76, 95%CI: 1.27–2.44, p  < 0.001 in fully adjusted model), stroke (HR = 1.69, 95%CI: 1.17–2.45, p  = 0.005) and MI (HR = 2.82, 95%CI: 1.18–6.72, p  = 0.019). But not a significant association was observed between cumulative AIP and cardiovascular mortality. In subgroup analysis, the association of cumulative AIP and the incidence of stroke was more pronounced in the elderly (HR: 0.89 vs. 2.41 for the age groups < 65 years and ≥ 65 years, p for interaction = 0.018). Conclusions A higher cumulative AIP was significantly associated with an increased risk of MACE, stroke and MI independent of traditional cardiovascular risk factors in a community-based population, and the association of cumulative AIP and stroke was particularly pronounced in the elderly population.

Background Inter-leg systolic blood pressure difference (ILSBPD) has emerged as a novel cardiovascular risk factor. This study aims to investigate the predictive value of ILSBPD on all-cause and cardiovascular mortality in general population. Methods We combined three cycles (1999–2004) of the National Health and Nutrition Examination Survey (NHANES) data. Levels of ILSBPD were calculated and divided into four groups based on three cut-off values of 5, 10 and 15mmHg. Time-to-event curves were estimated with the use of the Kaplan-Meier method, and two multivariable Cox proportional hazards regression models were conducted to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and cardiovascular mortality associated with ILSBPD. Results A total of 6 842 subjects were included, with the mean (SD) age of 59.5 (12.8) years. By December 31, 2019, 2 544 and 648 participants were identified all-cause and cardiovascular mortality respectively during a median follow-up of 16.6 years. Time-to-event analyses suggested that higher ILSBPD was associated with increased all-cause and cardiovascular mortality (logrank, p  < 0.001). Every 5mmHg increment of ILSBPD brings about 5% and 7% increased risk of all-cause and cardiovascular mortality, and individuals with an ILSBPD ≥ 15mmHg were significantly associated with higher incidence of all-cause mortality (HR 1.43, 95%CI 1.18–1.52, p  < 0.001) and cardiovascular mortality (HR 1.73, 95%CI 1.36–2.20, p  < 0.001) when multiple confounding factors were adjusted. Subgroup and sensitivity analysis confirmed the relationship. Conclusions Our findings suggest that the increment of ILSBPD was significantly associated with higher risk of all-cause and cardiovascular mortality in general population.

Background Currently, the major treatment modalities of advanced melanoma are immune check point and mitogen-activated protein kinase (MAPK) pathway inhibitors. As lacking head-to-head randomizedcontrolled trials (RCTs) comparing immune check point and MAPK pathway inhibitors, we evaluated the efficacy and toxicity with different treatment combinations of immune check point or MAPK pathway inhibitors for advanced melanoma by network meta-analysis. Methods We searched for RCTs in Pubmed, Embase, Ovid MEDLINE, Web of Science and Cochrane Central Register for Controlled Trials through March 2017. Two reviewers performed a network meta-analysis by assessing the hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), as well as by evaluating serious adverse events (SAEs). Results Twenty-four eligible RCTs involving 10,951 patients assigned to 11 treatment modalities were included. The combination of BRAF and MEK inhibitors demonstrated an improved OS benefit compared with all the other treatments except programmed death-1/ligand-1 (PD-1/L1) blockade because the difference in OS between the BRAF-MEK inhibitor combination and PD-1 blockade (HR: 0.85; 95% credible interval (CrI): 0.59, 1.21) was not significant. For PFS, the BRAF and MEK inhibitor combination showed a significant advantage compared with other treatments apart from the combination of PD-1/L1 and cytotoxic T lymphocyte-associated antigen-4(CTLA-4) blockade (HR:0.61; 95% CrI: 0.30, 1.25). The MEK inhibitor combined with chemotherapy was associated with the highest risk of SAEs (HR: 1.76 95% CrI: 1.21, 2.48). Conclusions The combination of BRAF and MEK inhibitors exhibited a survival advantage in OS and PFS and comparable risk of toxicity compared with chemotherapy.