Ocean internal tides suppress tropical cyclones in the South China Sea.

Tropical Cyclones (TCs) are devastating natural disasters. Analyzing four decades of global TC data, here we find that among all global TC-active basins, the South China Sea (SCS) stands out as particularly difficult ocean for TCs to intensify, despite favorable atmosphere and ocean conditions. Over the SCS, TC intensification rate and its probability for a rapid intensification (intensification by ≥ 15.4 m s-1 day-1) are only 1/2 and 1/3, respectively, of those for the rest of the world ocean. Originating from complex interplays between astronomic tides and the SCS topography, gigantic ocean internal tides interact with TC-generated oceanic near-inertial waves and induce a strong ocean cooling effect, suppressing the TC intensification. Inclusion of this interaction between internal tides and TC in operational weather prediction systems is expected to improve forecast of TC intensity in the SCS and in other regions where strong internal tides are present.

A quantitative systems pharmacology model of plasma kallikrein-kinin system dysregulation in hereditary angioedema.

Hereditary angioedema (HAE) due to C1-inhibitor deficiency is a rare, debilitating, genetic disorder characterized by recurrent, unpredictable, attacks of edema. The clinical symptoms of HAE arise from excess bradykinin generation due to dysregulation of the plasma kallikrein-kinin system (KKS). A quantitative systems pharmacology (QSP) model that mechanistically describes the KKS and its role in HAE pathophysiology was developed based on HAE attacks being triggered by autoactivation of factor XII (FXII) to activated FXII (FXIIa), resulting in kallikrein production from prekallikrein. A base pharmacodynamic model was constructed and parameterized from literature data and ex vivo assays measuring inhibition of kallikrein activity in plasma of HAE patients or healthy volunteers who received lanadelumab. HAE attacks were simulated using a virtual patient population, with attacks recorded when systemic bradykinin levels exceeded 20 pM. The model was validated by comparing the simulations to observations from lanadelumab and plasma-derived C1-inhibitor clinical trials. The model was then applied to analyze the impact of nonadherence to a daily oral preventive therapy; simulations showed a correlation between the number of missed doses per month and reduced drug effectiveness. The impact of reducing lanadelumab dosing frequency from 300 mg every 2 weeks (Q2W) to every 4 weeks (Q4W) was also examined and showed that while attack rates with Q4W dosing were substantially reduced, the extent of reduction was greater with Q2W dosing. Overall, the QSP model showed good agreement with clinical data and could be used for hypothesis testing and outcome predictions.

Transcription factor EHF drives cholangiocarcinoma development through transcriptional activation of glioma-associated oncogene homolog 1 and chemokine CCL2.

Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation-specific homologous factor (EHF), a member of the E26 transformation-specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma-associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor-associated macrophages (TAMs) through the C-C motif chemokine 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co-expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF-mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2-TAMs to inhibit EHF-driven CCA development.

Fam96a is essential for the host control of Toxoplasma gondii infection by fine-tuning macrophage polarization via an iron-dependent mechanism.

BACKGROUND: Toxoplasmosis affects a quarter of the world's population. Toxoplasma gondii (T.gondii) is an intracellular parasitic protozoa. Macrophages are necessary for proliferation and spread of T.gondii by regulating immunity and metabolism. Family with sequence similarity 96A (Fam96a; formally named Ciao2a) is an evolutionarily conserved protein that is highly expressed in macrophages, but whether it play a role in control of T. gondii infection is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we utilized myeloid cell-specific knockout mice to test its role in anti-T. gondii immunity. The results showed that myeloid cell-specific deletion of Fam96a led to exacerbate both acute and chronic toxoplasmosis after exposure to T. gondii. This was related to a defectively reprogrammed polarization in Fam96a-deficient macrophages inhibited the induction of immune effector molecules, including iNOS, by suppressing interferon/STAT1 signaling. Fam96aregulated macrophage polarization process was in part dependent on its ability to fine-tuning intracellular iron (Fe) homeostasis in response to inflammatory stimuli. In addition, Fam96a regulated the mitochondrial oxidative phosphorylation or related events that involved in control of T. gondii. CONCLUSIONS/SIGNIFICANCE: All these findings suggest that Fam96a ablation in macrophages disrupts iron homeostasis and inhibits immune effector molecules, which may aggravate both acute and chronic toxoplasmosis. It highlights that Fam96a may autonomously act as a critical gatekeeper of T. gondii control in macrophages.

A pseudo-response approach to constructing confidence intervals for the subset of patients expected to benefit from a new treatment.

In precision medicine, there is much interest in estimating the expected-to-benefit (EB) subset, i.e. the subset of patients who are expected to benefit from a new treatment based on a collection of baseline characteristics. There are many statistical methods for estimating the EB subset, most of which produce a 'point estimate' without a confidence statement to address uncertainty. Confidence intervals for the EB subset have been defined only recently, and their construction is a new area for methodological research. This article proposes a pseudo-response approach to EB subset estimation and confidence interval construction. Compared to existing methods, the pseudo-response approach allows us to focus on modelling a conditional treatment effect function (as opposed to the conditional mean outcome given treatment and baseline covariates) and is able to incorporate information from baseline covariates that are not involved in defining the EB subset. Simulation results show that incorporating such covariates can improve estimation efficiency and reduce the size of the confidence interval for the EB subset. The methodology is applied to a randomized clinical trial comparing two drugs for treating HIV infection.

DenseNet model incorporating hybrid attention mechanisms and clinical features for pancreatic cystic tumor classification.

PURPOSE: The aim of this study is to develop a deep learning model capable of discriminating between pancreatic plasma cystic neoplasms (SCN) and mucinous cystic neoplasms (MCN) by leveraging patient-specific clinical features and imaging outcomes. The intent is to offer valuable diagnostic support to clinicians in their clinical decision-making processes. METHODS: The construction of the deep learning model involved utilizing a dataset comprising abdominal magnetic resonance T2-weighted images obtained from patients diagnosed with pancreatic cystic tumors at Changhai Hospital. The dataset comprised 207 patients with SCN and 93 patients with MCN, encompassing a total of 1761 images. The foundational architecture employed was DenseNet-161, augmented with a hybrid attention mechanism module. This integration aimed to enhance the network's attentiveness toward channel and spatial features, thereby amplifying its performance. Additionally, clinical features were incorporated prior to the fully connected layer of the network to actively contribute to subsequent decision-making processes, thereby significantly augmenting the model's classification accuracy. The final patient classification outcomes were derived using a joint voting methodology, and the model underwent comprehensive evaluation. RESULTS: Using the five-fold cross validation, the accuracy of the classification model in this paper was 92.44%, with an AUC value of 0.971, a precision rate of 0.956, a recall rate of 0.919, a specificity of 0.933, and an F1-score of 0.936. CONCLUSION: This study demonstrates that the DenseNet model, which incorporates hybrid attention mechanisms and clinical features, is effective for distinguishing between SCN and MCN, and has potential application for the diagnosis of pancreatic cystic tumors in clinical practice.

Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment.

Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.

Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.

Optimizing Microfluidic Impedance Cytometry by Bypass Electrode Layout Design.

Microfluidic impedance cytometry (MIC) has emerged as a popular technique for single-cell analysis. Traditional MIC electrode designs consist of a pair of (or three) working electrodes, and their detection performance needs further improvements for microorganisms. In this study, we designed an 8-electrode MIC device in which the center pair was defined as the working electrode, and the connection status of bypass electrodes could be changed. This allowed us to compare the performance of layouts with no bypasses and those with floating or grounding electrodes by simulation and experiment. The results of detecting Φ 5 µm beads revealed that both the grounding and the floating electrode outperformed the no bypass electrode, and the grounding electrode demonstrated the best signal-to-noise ratio (SNR), coefficient of variation (CV), and detection sensitivity. Furthermore, the effects of different bypass grounding areas (numbers of grounding electrodes) were investigated. Finally, particles passing at high horizontal positions can be detected, and Φ 1 µm beads can be measured in a wide channel (150 µm) using a fully grounding electrode, with the sensitivity of bead volume detection reaching 0.00097%. This provides a general MIC electrode optimization technology for detecting smaller particles, even macromolecular proteins, viruses, and exosomes in the future.

Hypervolume Niche Dynamics and Global Invasion Risk of Phenacoccus solenopsis under Climate Change.

As a globally invasive quarantine pest, the cotton mealybug, Phenacoccus solenopsis, is spreading rapidly, posing serious threats against agricultural and forestry production and biosecurity. In recent years, the niche conservatism hypothesis has been widely debated, which is particularly evident in invasive biology research. Identifying the niche dynamics of P. solenopsis, as well as assessing its global invasion risk, is of both theoretical and practical importance. Based on 462 occurrence points and 19 bioclimatic variables, we used n-dimensional hypervolume analysis to quantify the multidimensional climatic niche of this pest in both its native and invasive ranges. We examined niche conservatism and further optimized the MaxEnt model parameters to predict the global invasion risk of P. solenopsis under both current and future climate conditions. Our findings indicated that the niche hypervolume of this pest in invasive ranges was significantly larger than that in its native ranges, with 99.45% of the niche differentiation contributed by niche expansion, with the remaining less than 1% explained by space replacement. Niche expansion was most evident in Oceania and Eurasia. The area under the receiver operating characteristic curve (0.83) and true skill statistic (0.62) indicated the model's robust performance. The areas of suitable habitats for P. solenopsis are increasing significantly and the northward spread is obvious in future climate change scenarios. North Africa, northern China, Mediterranean regions, and northern Europe had an increased invasion risk of P. solenopsis. This study provided scientific support for the early warning and control of P. solenopsis.

Feeding Appropriate Nutrients during the Adult Stage to Promote the Growth and Development of Carposina sasakii Offspring.

Nutrients consumed during the adult stage are a key factor affecting the growth, development, and reproduction of insect offspring and thus could play an important role in insect population research. However, there is absence of conclusive evidence regarding the direct effects of parental (F0) nutritional status on offspring (F1) fitness in insects. Carposina sasakii Matsumura is a serious, widespread fruit-boring pest that negatively impacts orchards and the agricultural economy across East Asia. In this study, life history data of F1 directly descended from F0C. sasakii fed with seven different nutrients (water as control, 5 g·L-1 honey solution, 10 g·L-1 honey solution, 5 g·L-1 sucrose solution, 10 g·L-1 sucrose solution, 15 g·L-1 sucrose solution, and 20 g·L-1 sucrose solution) were collected under laboratory conditions. The growth and development indices, age-stage specific survival rate, age-stage specific fecundity, age-stage specific life expectancy, age-stage specific reproductive value, and population parameters of these offspring were analyzed according to the age-stage, two-sex life table theory. The results showed that the nutritional status of F0 differentially affects the growth, development, and reproduction of F1. The F1 offspring of F0 adult C. sasakii fed with 10 g·L-1 sucrose had significantly higher life table parameters than those of other treatments (intrinsic rate of increase, r = 0.0615 ± 0.0076; finite rate of increase, λ = 1.0634 ± 0.0081; net reproductive rate, R0 = 12.61 ± 3.57); thus, 10 g·L-1 sucrose was more suitable for raising C. sasakii in the laboratory than other treatments. This study not only provides clear evidence for the implications of altering F0 nutritional conditions on the fitness of F1 in insects, but also lays the foundation for the implementation of feeding technologies within the context of a well-conceived laboratory rearing strategy for C. sasakii.

Comprehensive analysis of histophysiology, transcriptome and metabolome tolerance mechanisms in black porgy (Acanthopagrus schlegelii) under low temperature stress.

Low temperature stress has adverse effects on fish growth and reproduction, causing huge economic losses to the aquaculture industry. Especially, black porgy (Acanthopagrus schlegelii) farming industry in north of Yangtze River has been severely affected by low temperature for a long time. To explore the tolerance mechanism of black porgy to low temperature stress, the experiment was designed. The liver and gill tissues of black porgy were taken from the water temperature point of 15 °C (control group named as CG), 3.8 °C (cold sensitive group named as CS) and 2.8 °C (cold tolerant group named as CT) with a cooling rate of 3 °C/d from 15 °C for histophysiology, transcriptomics and metabolomics analysis. After cold stress, the histological results showed that the nucleus of the black porgy liver tissue appeared swelling, the cell arrangement was disordered; meanwhile the gill lamellae were twisted and broken, the epidermis was detached and aneurysm appeared. In addition, the expression of antioxidant, glucose metabolism and immune-related enzymes in the liver and gill of black porgy also changed significantly after low temperature stress. By analyzing the transcriptome and metabolome dates of black porgy liver, 3474 differentially expressed genes (DEGs) and 689 differentially expressed metabolites (DEMs) involved in low temperature stress were identified, respectively. The results of the transcriptome and metabolome combined analysis showed that individuals in the CS group mainly supplied energy to the body through lipid metabolism and amino acid metabolism, and meanwhile the apoptosis pathway was activated. While, individuals in the CT group mainly through glucose metabolism and steroid hormone biosynthesis to supply energy for the body. The validation results of qPCR on eight functional genes further demonstrated the reliability of RNA-Seq data. In summary, the results provide molecular information about adaptation to climate change and genetic selection of black porgy.

Amplifying dual-visible-light photoswitching in aqueous media via confinement promoted triplet-triplet energy transfer.

Achieving visible-light photochromism is a long-term goal of chemists keen to exploit the opportunities of molecular photoswitches in multi-disciplinary research studies. Triplet-sensitization offers a flexible approach to building diverse visible-light photoswitches using existing photochromic scaffolds, circumventing the need for sophisticated molecular design and synthesis. Unfortunately, distance-dependence and environment-sensitivity of triplet-excited species remain as key challenges that severely impair sensitization efficiency and limit their practical availability. We present herein a nature-inspired nanoconfinement strategy in which a triplet-sensitized visible-light photoswitch/sensitizer system is assembled into nanoconfined micelles (d ∼ 40 nm). A ca. 10-fold efficiency increase of triplet-triplet energy transfer for photochromism as well as an amplified fluorescence on/off contrast upon bi-directional visible-light excitation (470/560 nm) was achieved in full aqueous media. By virtue of this, the hybrid photoswitchable system is successfully applied for both flash information encryption and multiple dynamic cell imaging assays, further proving its versatility in materials and life science.

Comparative physiological, biochemical, metabolomic, and transcriptomic analyses reveal the formation mechanism of heartwood for Acacia melanoxylon.

Acacia melanoxylon is well known as a valuable commercial tree species owing to its high-quality heartwood (HW) products. However, the metabolism and regulatory mechanism of heartwood during wood development remain largely unclear. In this study, both microscopic observation and content determination proved that total amount of starches decreased and phenolics and flavonoids increased gradually from sapwood (SW) to HW. We also obtained the metabolite profiles of 10 metabolites related to phenolics and flavonoids during HW formation by metabolomics. Additionally, we collected a comprehensive overview of genes associated with the biosynthesis of sugars, terpenoids, phenolics, and flavonoids using RNA-seq. A total of ninety-one genes related to HW formation were identified. The transcripts related to plant hormones, programmed cell death (PCD), and dehydration were increased in transition zone (TZ) than in SW. The results of RT-PCR showed that the relative expression level of genes and transcription factors was also high in the TZ, regardless of the horizontal or vertical direction of the trunk. Therefore, the HW formation took place in the TZ for A. melanoxylon from molecular level, and potentially connected to plant hormones, PCD, and cell dehydration. Besides, the increased expression of sugar and terpenoid biosynthesis-related genes in TZ further confirmed the close connection between terpenoid biosynthesis and carbohydrate metabolites of A. melanoxylon. Furthermore, the integrated analysis of metabolism data and RNA-seq data showed the key transcription factors (TFs) regulating flavonoids and phenolics accumulation in HW, including negative correlation TFs (WRKY, MYB) and positive correlation TFs (AP2, bZIP, CBF, PB1, and TCP). And, the genes and metabolites from phenylpropanoid and flavonoid metabolism and biosynthesis were up-regulated and largely accumulated in TZ and HW, respectively. The findings of this research provide a basis for comprehending the buildup of metabolites and the molecular regulatory processes of HW formation in A. melanoxylon.

Attention-guided variational graph autoencoders reveal heterogeneity in spatial transcriptomics.

The latest breakthroughs in spatially resolved transcriptomics technology offer comprehensive opportunities to delve into gene expression patterns within the tissue microenvironment. However, the precise identification of spatial domains within tissues remains challenging. In this study, we introduce AttentionVGAE (AVGN), which integrates slice images, spatial information and raw gene expression while calibrating low-quality gene expression. By combining the variational graph autoencoder with multi-head attention blocks (MHA blocks), AVGN captures spatial relationships in tissue gene expression, adaptively focusing on key features and alleviating the need for prior knowledge of cluster numbers, thereby achieving superior clustering performance. Particularly, AVGN attempts to balance the model's attention focus on local and global structures by utilizing MHA blocks, an aspect that current graph neural networks have not extensively addressed. Benchmark testing demonstrates its significant efficacy in elucidating tissue anatomy and interpreting tumor heterogeneity, indicating its potential in advancing spatial transcriptomics research and understanding complex biological phenomena.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Effects of Dietary Inosine 5'-Monophosphate Supplementation on the Growth Performance and Salinity and Oxidative Stress Resistance of Gibel Carp (Carassius auratus gibelio).

An 88-day feeding trial was conducted to evaluate the effects of dietary inosine 5'-monophosphate (5'-IMP) on the growth performance and salinity and oxidative stress resistance in the juvenile gibel carp CAS III (Carassius auratus gibelio; initial body weight: 7.48 g). Four isonitrogenous and isoenergetic diets containing exogenous 5'-IMP were formulated. P1, P2, P3 and P4 were diets containing 5'-IMP at four concentrations (0, 1, 2 and 4 g kg-1). The four diets were randomly allotted to triplicate tanks in a recirculating system. After the feeding trial, six fish per tank were netted randomly and placed into 12‱ saline water to test their response to salinity stress. The results indicated that the feed conversion rate was enhanced by dietary supplementation with 5'-IMP. The appetite, plasma neuropeptide Y level and feeding rate of the P3 group were lower than those in the control treatment group. Dietary supplementation with 5'-IMP improved the osmoregulatory adaptation of gibel carp under acute salinity stress. Six hours after the salinity stress treatment, in the dietary 5'-IMP treatment group, the plasma cortisol and K+ concentrations were lower and the Na+/K+-ATPase activity was greater than that in the control group. Dietary supplementation with 5'-IMP promoted the expression of the glucocorticoid receptors NKA-α1b and NKCC and retarded the expression of Hsp70 in P4-treated gill filaments and kidneys. Dietary supplementation with 5'-IMP resulted in a stable oxidative-stress-resistant phenotype characterized by increased levels of cellular antioxidants, including SOD, catalase, glutathione peroxidase, glutathione reductase and MPO. The above results of the current study demonstrate that supplementation of 5'-IMP can promote feed utilization and have positive influences on the salinity and oxidative stress resistance of gibel carp.

Flexible Tactile Sensors for 3D Force Detection.

As tactile force sensing has become increasingly significant in the field of machine haptics, achieving multidimensional force sensing remains a challenge. We propose a 3D flexible force sensor that consists of an axisymmetric hemispherical protrusion and four equally sized quarter-circle electrodes. By simulating the device using a force and electrical field model, it has been found that the magnitude and direction of the force can be expressed through the voltage relationship of the four electrodes when the magnitude of the shear force remains constant and its direction varies within 0-360°. The experimental results show that a resolution of 15° can be achieved in the range 0-90°. Additionally, we installed the sensor on a robotic hand, enabling it to perceive the magnitude and direction of touch and grasp actions. Based on this, the designed 3D flexible tactile force sensor provides valuable insights for multidimensional force detection and applications.

Assessing the causal associations of different types of statins use and knee/hip osteoarthritis: A Mendelian randomization study.

OBJECTIVE: This study comprehensively evaluated the causal relationship between different types of statins use and knee/hip osteoarthritis (OA) using a two-sample and multivariate Mendelian randomization (MR) method. METHODS: MR analysis was conducted using publicly available summary statistics data from genome-wide association studies (GWAS) to assess the causal associations between total statins use (including specific types) and knee/hip OA. The primary analysis utilized the inverse variance-weighted (IVW) method, with sensitivity analysis conducted to assess robustness. Multivariable MR (MVMR) analysis adjusted for low-density lipoprotein cholesterol (LDL-C), intermediate-density lipoprotein cholesterol (IDL-C), high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI). RESULTS: The MR analysis revealed a significant inverse association between genetically predicted total statins use and the risk of knee OA (OR = 0.950, 95%CI: 0.920-0.982, p = 0.002) as well as hip OA (OR = 0.932, 95%CI: 0.899-0.966, p <0.001). Furthermore, this study highlighted a reduced risk of knee/hip OA with the use of atorvastatin and simvastatin. Rosuvastatin use was associated with a decreased risk of hip OA but showed no association with knee OA. MVMR results indicated no correlation between exposure factors and outcomes after adjusting for LDL-C or IDL-C. HDL-C may not significantly contribute to statin-induced osteoarthritis, while BMI may play an important role. CONCLUSION: This study provides compelling evidence of the close relationship between statin use and a reduced risk of knee/hip OA, particularly with atorvastatin and simvastatin. LDL-C and IDL-C may mediate these effects. These findings have important implications for the clinical prevention and treatment of knee/hip OA.