FPLS-DC: functional partial least squares through distance covariance for imaging genetics.

MOTIVATION: Imaging genetics integrates imaging and genetic techniques to examine how genetic variations influence the function and structure of organs like the brain or heart, providing insights into their impact on behavior and disease phenotypes. The use of organ-wide imaging endophenotypes has increasingly been used to identify potential genes associated with complex disorders. However, analyzing organ-wide imaging data alongside genetic data presents two significant challenges: high dimensionality and complex relationships. To address these challenges, we propose a novel, nonlinear inference framework designed to partially mitigate these issues. RESULTS: We propose a functional partial least squares through distance covariance (FPLS-DC) framework for efficient genome wide analyses of imaging phenotypes. It consists of two components. The first component utilizes the FPLS-derived base functions to reduce image dimensionality while screening genetic markers. The second component maximizes the distance correlation between genetic markers and projected imaging data, which is a linear combination of the FPLS-basis functions, using simulated annealing algorithm. In addition, we proposed an iterative FPLS-DC method based on FPLS-DC framework, which effectively overcomes the influence of inter-gene correlation on inference analysis. We efficiently approximate the null distribution of test statistics using a gamma approximation. Compared to existing methods, FPLS-DC offers computational and statistical efficiency for handling large-scale imaging genetics. In real-world applications, our method successfully detected genetic variants associated with the hippocampus, demonstrating its value as a statistical toolbox for imaging genetic studies. AVAILABILITY AND IMPLEMENTATION: The FPLS-DC method we propose opens up new research avenues and offers valuable insights for analyzing functional and high-dimensional data. In addition, it serves as a useful tool for scientific analysis in practical applications within the field of imaging genetics research. The R package FPLS-DC is available in Github: https://github.com/BIG-S2/FPLSDC.

Long noncoding RNA Glis2 regulates podocyte mitochondrial dysfunction and apoptosis in diabetic nephropathy via sponging miR-328-5p.

Podocyte apoptosis exerts a crucial role in the pathogenesis of DN. Recently, long noncoding RNAs (lncRNAs) have been gradually identified to be functional in a variety of different mechanisms associated with podocyte apoptosis. This study aimed to investigate whether lncRNA Glis2 could regulate podocyte apoptosis in DN and uncover the underlying mechanism. The apoptosis rate was detected by flow cytometry. Mitochondrial membrane potential (ΔΨM) was measured using JC-1 staining. Mitochondrial morphology was detected by MitoTracker Deep Red staining. Then, the histopathological and ultrastructure changes of renal tissues in diabetic mice were observed using periodic acid-Schiff (PAS) staining and transmission electron microscopy. We found that lncRNA Glis2 was significantly downregulated in high-glucose cultured podocytes and renal tissues of db/db mice. LncRNA Glis2 overexpression was found to alleviate podocyte mitochondrial dysfunction and apoptosis. The direct interaction between lncRNA Glis2 and miR-328-5p was confirmed by dual luciferase reporter assay. Furthermore, lncRNA Glis2 overexpression alleviated podocyte apoptosis in diabetic mice. Taken together, this study demonstrated that lncRNA Glis2, acting as a competing endogenous RNA (ceRNA) of miRNA-328-5p, regulated Sirt1-mediated mitochondrial dysfunction and podocyte apoptosis in DN.

Merging or ensembling: integrative analysis in multiple neuroimaging studies.

The aim of this paper is to systematically investigate merging and ensembling methods for spatially varying coefficient mixed effects models (SVCMEM) in order to carry out integrative learning of neuroimaging data obtained from multiple biomedical studies. The "merged" approach involves training a single learning model using a comprehensive dataset that encompasses information from all the studies. Conversely, the "ensemble" approach involves creating a weighted average of distinct learning models, each developed from an individual study. We systematically investigate the prediction accuracy of the merged and ensemble learners under the presence of different degrees of interstudy heterogeneity. Additionally, we establish asymptotic guidelines for making strategic decisions about when to employ either of these models in different scenarios, along with deriving optimal weights for the ensemble learner. To validate our theoretical results, we perform extensive simulation studies. The proposed methodology is also applied to 3 large-scale neuroimaging studies.

Synthesis, crystal structure and investigation of ion-exchange possibility for sodium tellurate NaTeO3(OH).

A new sodium tellurate has been hydrothermally synthesized and comprehensively analysed using spectroscopic and thermogravimetric techniques, resulting in the determination of its composition as NaTeO3(OH). The analysis of synchrotron X-ray and neutron diffraction data indicates that NaTeO3(OH) has a crystal structure similar to that of the previously reported tellurate, KTeO3(OH), with the space group P21/a (No. 14). NaTeO3(OH) consists of zigzag one-dimensional chains built by edge-sharing TeO6 octahedra, running parallel to the c-axis and connected to sodium and hydrogen atoms. The hydrogen atoms covalently bond to the terminal oxygen atoms on the one-dimensional chain and also form hydrogen bonds with other terminal oxygen atoms on nearby chains. The structure has been confirmed by optimization using the pseudopotential method and performing Bond Valence Sum (BVS) analysis. Although Li+ ions in LiTeO3(OH) can be exchanged reversibly with H+ ions, no ion exchange behaviour is observed in NaTeO3(OH). The difference is attributed to the size of the alkali ions and their crystal structure.

Clinical application value of Ultrafast Pulse Wave Velocity in early cardiovascular injury of Immunoglobulin A nephropathy.

AIM: To investigate the application and the related influencing factors of ultrafast pulse wave velocity (ufPWV) in the evaluation of carotid artery elasticity in patients with Immunoglobulin A nephropathy (IgAN). MATERIAL AND METHODS: A total of 156 IgAN patients and 50 healthy individuals were selected as the control group. The ufPWV technique was employed to measure carotid arterial elasticity parameters, including carotid intima-media thickness (cIMT), pulse wave velocity at the beginning of systole (BS-PWV) and pulse wave velocity at the end of systole (ES-PWV). RESULTS: Across the three groups (control group, IgAN patients with normal renal function, and IgAN patients with renal dysfunction) there was an increasing trend observed in cIMT, BS-PWV, and ES-PWV. Additionally, ES-PWV exhibited higher sensitivity than BS-PWV. Correlation analysis revealed that BS-PWV and ES-PWV were positively correlated with age, body mass index (BMI), systolic blood pressure (SBP), high-sensitivity C-reactive protein (hs-CRP), creatinine (Cr), blood urea nitrogen (BUN), and uric acid (UA) and negatively correlated with estimated glomerular filtration rate (eGFR). CONCLUSION: The ufPWV technique allows for the rapid and direct measurement of arterial elasticity parameters in the neck and represents a novel approach for the early diagnosis and quantitative assessment of arterial stiffness risk in IgAN patients.

Angucyclinones with IDO and TDO inhibitory activities isolated from the actinomycetes Umezawaea beigongshangensis.

Four previously undescribed angucyclinones umezawaones A-D (1-4) were isolated from the liquid cultures of Umezawaea beigongshangensis. Their structures were determined by spectroscopic analyses, single crystal X-ray diffraction, quantum chemical 13C NMR and electronic circular dichroism calculations. All compounds displayed strong inhibitory activities against indoleamine 2,3-dioxygenase and tryptophan-2,3-dioxygenase in enzymatic assay, especially compound 2.

[Value of contrast-enhanced percutaneous ultrasound in the diagnosis of rotator cuff tear subtype].

OBJECTIVE: To explore characteristics of contrast-enhanced ultrasound (CEUS) images features and diagnostic value of rotator cuff tear subtypes. METHODS: From January 2019 to March 2022, percutaneous ultrasound-guided subacromial bursography (PUSB) with persutaneous ultrasound-guide tendon lesionography (PUTL) was performed on 114 patients with suspected rotator cuff injury were evaluated, including 54 males and 60 females ranged in age from 35 to 75 years old with an average of (58.8±8.7 ) years old;76 patients on the right side and 38 patients on the left side;the course of disease ranged from 0.13 to 111 months with an average of (10.2±9.8) months. GE LOGIQ E9 color doppler ultrasound diagnostic high frequency(6 to 12 MHz) was used to CEUS Using arthroscopy as gold standard, receiver operating characteristic (ROC) curve was used to evaluate diagnostic efficacy of US, MRI and CEUS for rotator cuff injury, also sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. RESULTS: The sensitivity of US in diagnosing full-thickness tears was 72.1%, specificity was 93.0%, and accuracy was 85.1%. The sensitivity, specificity and accuracy of MRI diagnosis of full-thickness tear were 90.9%, 92.6% and 92.1% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of full-thickness tear were 100%. The sensitivity, specificity and accuracy of US in the diagnosis of partial tear were 85.7%, 77.2% and 79.8% respectively. The sensitivity, specificity and accuracy of MRI diagnosis of partial tear were 83.7%, 81.7% and 82.5% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of partial tear were 95.7%, 92.6% and 93.9% respectively. There were significant differences in diagnosis results of US, MRI and CEUS for rotator cuff bursa tear (P<0.001). Kapp test showed good consistency between CEUS and arthroscopy in diagnosing rotator cuff tear subtypes (full-thickness and partial tears). CONCLUSION: Using PUSB/PUTL to observe distribution of contrast media in bursa, tendon and joint cavity to evaluate the type of rotator cuff tear, its diagnostic performance is significantly better than US and MRI. Therefore, percutaneous contrast-enhanced ultrasound can be a reliable method for diagnosing subtypes of rotator cuff tears.

Effect of Chinese Medicines combined with transarterial chemoembolization on primary hepatic carcinoma: A systematic review and meta-analysis.

BACKGROUND: To systematically evaluate the survival rate and postoperative adverse reactions of patients with hepatocellular carcinoma treated with traditional Chinese medicine combined with TACE by meta-analysis. METHODS: Four major literature databases (Cochrane Library, Embase, PubMed, and Web of Science) were retrieved to collect published English articles since 2009. After determining the random effect model or fixed utility model based on a heterogeneity test, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: This meta-analysis included 8 prospective studies published between 2009 and 2019. Due to moderate heterogeneity (P < .05, I2 = 54.8%), Therefore, the random effect model is used to analyze the data, so as to explore the relationship between CMs combined with TACE treatment and survival rate and postoperative adverse reactions. All the comprehensive test results show that there is a statistical significance between CMs combined with TACE treatment and survival rate. (OR = 1.88, 95% CI 1.34-2.64, P = .03). Then subgroup analysis and sensitivity analysis were carried out. The results indicated that the overall results ranged from 1.12(95% CI = 1.03-1.11) to 1.21(95% CI = 1.22-1.33). CONCLUSIONS: The 1-year survival rate of patients treated with traditional Chinese medicine TACE is a protective factor, and the quality score included in the study affects the evaluation of the effective dose. At the same time, traditional Chinese medicine combined with TACE has nothing to do with the reduction of postoperative complications.

The Value of Percutaneous Ultrasound-Guided Subacromial Bursography for Rotator Cuff Tear in Elderly Patients with Shoulder Pain.

Objective: Based on the analysis of the images of acromial slide, we explored the application of percutaneous ultrasound-guided subacromial bursography (PUSB) on rotator cuff tear (RCT) in diagnosing elderly patients with shoulder pain. Methods: Eighty-five patients who were clinically diagnosed with RCT and underwent PUSB examination in the department of ultrasound in our hospital were enrolled as the subjects. Independent samples t-test was used to analyze the general characteristics. Based on the gold standard of shoulder arthroscopy, the diagnostic efficacy of ultrasound, magnetic resonance imaging (MRI), and PUSB was evaluated. The sensitivity, specificity, positive and negative predictive values, and accuracy were calculated as well. The consistency of these techniques with shoulder arthroscopy in diagnosing the RCT stage was additionally compared using Kappa test. Results: In patients with large full-thickness RCT, the 100% detection rate was achieved by the techniques of ultrasound, MRI, and PUSB. For patients with small full-thickness RCT, the detection rate of PUSB (100%) was evidently higher than those of ultrasound and MRI. Similar results were shown in the detection rates of patients with bursal-side partial-thickness RCT (90.5%) and articular-side partial-thickness RCT (86.9%). More importantly, the sensitivity, specificity, and accuracy of PUSB in patients with both full-thickness RCT and partial-thickness RCT were significantly better than those of ultrasound and MRI. Conclusion: PUSB has a better efficacy in the detection of RCT than ultrasound and MRI, showing its feasibility as an important imaging method to evaluate the degree of RCT.

Osmotic cleaning of typical inorganic and organic foulants on reverse osmosis membrane for textile printing and dyeing wastewater treatment.

Reverse osmosis (RO) is one of the most fundamental membrane technology because it has higher salt rejections, which suffers from the issue of membrane fouling, as the membrane is inevitably exposed to foulants during the filtration process. For different fouling mechanisms of RO membrane, physical and chemical cleaning are widely used in the control of RO membrane fouling. The present study investigated the performance and water flux recovery using osmotic cleaning to clean the typical inorganic and organic foulants on RO membrane for textile printing and dyeing wastewater treatment. The effects of operation conditions (i.e., the concentration of cleaning solution, the filtrating time and cleaning time, and the flow rate of cleaning solution) on relative water flux recovery were examined. The results show that a highly water flux recovery (98.3% for cleaning of inorganic fouling and 99.6% for cleaning of organic fouling) was achieved under optimal operation of the concentration and flow rate of cleaning solution and the filtrating and cleaning time. Moreover, the experiment of repeated "filtrating-cleaning" cycles indicated that the osmotic cleaning has highly performance of recoverability of water flux (over 95.0%) can be extended in a relatively long time. The experimental results and changes on SEM and AFM images of RO membrane confirmed the successful development and application of osmotic cleaning for inorganic and organic fouling of RO membrane.

Heart-brain connections: Phenotypic and genetic insights from magnetic resonance images.

Cardiovascular health interacts with cognitive and mental health in complex ways, yet little is known about the phenotypic and genetic links of heart-brain systems. We quantified heart-brain connections using multiorgan magnetic resonance imaging (MRI) data from more than 40,000 subjects. Heart MRI traits displayed numerous association patterns with brain gray matter morphometry, white matter microstructure, and functional networks. We identified 80 associated genomic loci (P < 6.09 × 10-10) for heart MRI traits, which shared genetic influences with cardiovascular and brain diseases. Genetic correlations were observed between heart MRI traits and brain-related traits and disorders. Mendelian randomization suggests that heart conditions may causally contribute to brain disorders. Our results advance a multiorgan perspective on human health by revealing heart-brain connections and shared genetic influences.

Four-dimensional mapping of dynamic longitudinal brain subcortical development and early learning functions in infants.

Brain subcortical structures are paramount in many cognitive functions and their aberrations during infancy are predisposed to various neurodevelopmental and neuropsychiatric disorders, making it highly essential to characterize the early subcortical normative growth patterns. This study investigates the volumetric development and surface area expansion of six subcortical structures and their associations with Mullen scales of early learning by leveraging 513 high-resolution longitudinal MRI scans within the first two postnatal years. Results show that (1) each subcortical structure (except for the amygdala with an approximately linear increase) undergoes rapid nonlinear volumetric growth after birth, which slows down at a structure-specific age with bilaterally similar developmental patterns; (2) Subcortical local area expansion reveals structure-specific and spatiotemporally heterogeneous patterns; (3) Positive associations between thalamus and both receptive and expressive languages and between caudate and putamen and fine motor are revealed. This study advances our understanding of the dynamic early subcortical developmental patterns.

Quantitative analysis of the contribution of sources, diffusion pathways, and receptor attributes for the spatial distribution of soil heavy metals and their nested structure analysis in China.

Investigation of heavy metal pollution degree, pollution sources, and spatial distribution structure is crucial for the country's soil pollution prevention, but relevant research is lacking. In this study, As, Cd, Cr, Cu, Pb and Zn in the national scope are taken as research objects. Among them, Cd has the highest pollution level. Four sources were quantitatively allocated as soil type, mining and dressing industry, GDP, and NDVI, which accounted for 92.93, 97.81, 99.30 and 96.24 % of Cr, Cd, Zn and As contamination, respectively. In addition, according to the geographical detector, the spatial distribution of As was affected by three diffusion pathways, whose influence degree were 0.822-0.947, especially the slope. Cadmium was primarily affected by both receptor attributes and diffusion pathways, with an influence degree of 0.010-0.175, especially soil water content and slope; Cr and Pb were affected by receptor attributes, with an influence degree of 0.886-0.986 and 0.007-0.288, respectively, especially for soil water content and soil organic carbon; Cu and Zn were affected by receptor attributes, with an influence degree of 0.182-0.823 and 0.002-0.150, respectively, especially for soil texture. There are two spatial distribution structures with nested scales in east-west and north-south directions. The large spatial structure has a more significant impact on the spatial distribution of heavy metals, especially in the east-west direction. Overall, the mining and dressing industry is the main source in Hunan, Yunnan, and Liaoning, where many mines exist and mining activities are frequent. GDP was the main source in Shanghai and Zhejiang areas, where the economy is developed. NDVI was the main source in Guangdong and Anhui areas, where agriculture is relatively developed. These results provide a basis for determining remediation and prevention objectives in soil pollution remediation and prevention in the national scope.

Insights into degradation of pharmaceutical pollutant atenolol via electrochemical advanced oxidation processes with modified Ti4O7 electrode: Efficiency, stability and mechanism.

A novel active Ce-doped Ti4O7 (Ti/Ti4O7-Ce) electrode was prepared and evaluated for improvement of the refractory pollutants degradation efficiency in Electrochemical advanced oxidation processes (EAOPs). The results showed that the addition of Ce in Ti/Ti4O7 electrode leading to great impact on •OH generation rate and electrode stability compared to pristine Ti/Ti4O7 electrode. Ti/Ti4O7-Ce electrode presented efficient oxidation capacity for pharmaceutical pollutant atenolol (ATL) in EAOPs, which could be attributed to the improvement of indirect oxidation mediated by electro-generated •OH, as the amount of •OH production was 16.5% higher than that in Ti/Ti4O7 within 120 min. The operational conditions greatly influenced the ATL degradation. The degradation efficiency of ATL increased as the current density, the degradation efficiency reached 100% under pH 4, but it just removed 81% of ATL under pH 10 after 120 min treatment. Results also suggested that the inhibiting effect from the ATL degradation was mostly associated with the decreased oxidation capacity induced by water hardness and natural organic matter (NOM). It displayed a satisfactory durability after 40 cycles of experimental detections in this research. The results of study suggested that Ti/Ti4O7-Ce was a promising electrode for the efficient degradation of PPCPs-polluted wastewater and provided constructive suggestion for the refractory pollutants of EAOPs.

Herpud1 deficiency alleviates homocysteine-induced aortic valve calcification.

OBJECTIVES: To evaluate the role and therapeutic value of homocysteine (hcy)-inducible endoplasmic reticulum stress (ERS) protein with ubiquitin like domain 1 (Herpud1) in hcy-induced calcific aortic valve disease (CAVD). BACKGROUND: The morbidity and mortality rates of calcific aortic valve disease (CAVD) remain high while treatment options are limited. METHODS: In vivo, we use the low-density lipoprotein receptor (LDLR) and Herpud1 double knockout (LDLR-/-/Herpud1-/-) mice and used high methionine diet (HMD) to assess of aortic valve calcification lesions, ERS activation, autophagy, and osteogenic differentiation of aortic valve interstitial cells (AVICs). In vitro, the role of Herpud1 in the Hcy-related osteogenic differentiation of AVICs was investigated by manipulating of Herpud1 expression. RESULTS: Herpud1 was highly expressed in calcified human and mouse aortic valves as well as primary aortic valve interstitial cells (AVICs). Hcy increased Herpud1 expression through the ERS pathway and promoted CAVD progression. Herpud1 deficiency inhibited hcy-induced CAVD in vitro and in vivo. Herpud1 silencing activated cell autophagy, which subsequently inhibited hcy-induced osteogenic differentiation of AVICs. ERS inhibitor 4-phenyl butyric acid (4-PBA) significantly attenuated aortic valve calcification in HMD-fed low-density lipoprotein receptor-/- (LDLR-/-) mice by suppressing ERS and subsequent Herpud1 biosynthesis. CONCLUSIONS: These findings identify a previously unknown mechanism of Herpud1 upregulation in Hcy-related CAVD, suggesting that Herpud1 silencing or inhibition is a viable therapeutic strategy for arresting CAVD progression. HIGHLIGHTS: • Herpud1 is upregulated in the leaflets of Hcy-treated mice and patients with CAVD. • In mice, global knockout of Herpud1 alleviates aortic valve calcification and Herpud1 silencing activates cell autophagy, inhibiting osteogenic differentiation of AVICs induced by Hcy. • 4-PBA suppressed Herpud1 expression to alleviate AVIC calcification in Hcy treated AVICs and to mitigate aortic valve calcification in mice.

Geopolitical Risk Evolution and Obstacle Factors of Countries along the Belt and Road and Its Types Classification.

As a great practice of building a community of shared future for mankind, the Belt and Road Initiative is facing geopolitical risk brought by great power games, regional conflicts and terrorism. It is an important mission of geopolitical research to scientifically deal with the geopolitical risk along the Belt and Road. This study systematically constructs the geopolitical risk assessment index system and analyzes the spatiotemporal evolution, obstacle factors and risk types of geopolitical risk of countries along the Belt and Road by using the entropy weight TOPSIS model, obstacle degree model and minimum variance method. The research results showed that: (1) From 2005 to 2020, the polarization of geopolitical risk in countries along the Belt and Road was very significant, and the overall trend of geopolitical risk tended to deteriorate. (2) The Middle East and Eastern Europe were the most important geopolitical risk zones along the Belt and Road, and Afghanistan, Iraq, Russia and Ukraine were the main high geopolitical risk centers, with significant risk spillover effects from these centers. (3) Terrorism and close relations with the United States were the most important obstacle factors for geopolitical risk in countries along the Belt and Road, and military intervention politics, trade dependence degree and foreign debt burden were important obstacle factors for geopolitical risk in countries along the Belt and Road. (4) Geopolitical risk along the Belt and Road can be divided into sovereign risk dominant type, sovereign and military risk dominant type, sovereign and major power intervention risk dominant type, and sovereign and military and major power intervention risk jointly dominated type, among which sovereign and military and major power intervention risk jointly dominated type was the most important geopolitical risk type. In order to scientifically deal with geopolitical risk in countries along the Belt and Road, it is necessary to strengthen geopolitical risk awareness, pay attention to the dominant geopolitical risk factors, strengthen the control of regional geopolitical risk spillover and formulate reasonable risk prevention and control scheme based on geopolitical risk types.

Advanced treatment of high-salinity wastewater by catalytic ozonation with pilot- and full-scale systems and the effects of Cu2+ in original wastewater on catalyst activity.

In this work, heterogeneous catalytic ozonation for the treatment of bio-treated saccharin sodium production wastewater (BSSW) was comprehensively investigated with pilot- and full-scale systems, with special emphasis on the effects of Cu2+ in the original wastewater on catalyst activity. The results of semi-batch and continuous experiments show that heterogeneous catalytic ozonation was effective in removing organic compounds from high-salinity wastewater and that Cu2+ in the original wastewater had a substantial effect on the performance of the process. The retention of 0.15 mM Cu2+ in BSSW increased the chemical oxygen demand (COD) removal by 31% in semi-batch reactor with heterogeneous catalytic ozonation. The stable COD removal efficiencies ranged from 74% to 66.4% for a 9-month operation, indicating that Cu2+ with an appropriate concentration in the original BSSW not only improved the COD removal efficiencies but also inhibited catalyst deactivation; catalyst deactivation was mainly caused by the deposition of inorganic salts on the catalyst surface. Cu2+ combined with some anions to inhibit the formation and deposition of inorganic salts that could easily cause deactivation. The deposited copper salts were readily eliminated, especially during backflushing operations. Moreover, in a full-scale study, heterogeneous catalytic ozonation with 0.15 mM Cu2+ in BSSW exhibited stable COD removal efficiencies (51%-83%) after over 3 years of operation. This study offers a new idea for using the inherent properties of wastewater to perform advanced treatments on high-salinity industrial wastewater through heterogeneous catalytic ozonation.

Hyaluronic acid microneedles loaded with curcumin nanodrugs and new indocyanine green inhibits human tongue squamous carcinoma cells in vitro.

OBJECTIVE: To prepare the hyaluronic acid microneedle (abbreviated as microneedle) delivery system carrying curcumin nanodrugs (Cur-NDs) and photothermal trigger agent new indocyanine green (IR820), and to investigate its effect on proliferation of human tongue squamous carcinoma cells (Cal-27) in vitro. METHODS: The microneedle delivery system carrying Cur-NDs and IR820 was prepared. The morphological characteristics of the microneedles were observed, and the mechanical strength test, skin insertion ability test and the photothermal test in vitro were performed. Cal-27 cells were treated with microneedles, Cur-NDs microneedles, IR820 microneedles, or Cur-NDs+IR820 microneedles in vitro, respectively. The IR820 microneedle group and Cur-NDs+IR820 microneedle group were irradiated with 808 nm near infrared light at 1 W/cm 2 for 5 min. The cell viability was tested with cell counting kit-8 method. RESULTS: The prepared microneedles had homogeneous needle-like morphology, good mechanical strength and skin piercing ability, among which the microneedles equipped with IR820 showed better photothermal performance. The survival rates of Cal-27 cells were 100.00% in blank control group, 99.92% in control microneedles group, 94.08% in Cur-NDs microneedles group, 0.41% in IR820 microneedles group, and 0.04% in Cur-NDs+IR820 microneedles group, respectively (all P<0.05). CONCLUSION: Compared with single drug treatment, Cur-NDs+IR820 microneedle shows better inhibitory effect on Cal-27 cell proliferation in vitro.

Correction: Hybrid cellulose nanocrystal/alginate/gelatin scaffold with improved mechanical properties and guided wound healing.

[This corrects the article DOI: 10.1039/C9RA04026A.].

Dynamics of protein condensates in weak-binding regime.

Weak complementary interactions between proteins and nucleic acids are the main driving forces of intracellular liquid-liquid phase separation. The sticker-spacer model has emerged as a unifying principle for understanding the phase behavior of these multivalent molecules. It remains elusive how specific interactions mediated by stickers contribute to the rheological properties of the liquid condensates. Previous studies have revealed that for strong binding strength ɛ_{b}, the bulk diffusivity D depends on the effective bond lifetime τ, viz., D∝τ^{-1}. Consequently, equal concentrations of the complementary stickers induce a slow down in the dynamics of the condensates D∝e^{-1.5ɛ_{b}}. However, for weak-binding strength, it is expected that the resulting condensates are dynamic, loose network liquids rather than kinetically arrested, compact clusters. We develop a mean-field theory using the thermodynamics of the associative polymers and perform molecular-dynamics simulations based on the sticker-spacer model to study the controlling factors in the structure and dynamics of such condensates in the weak-binding regime. Through scaling analysis, we delineate how the free sticker fraction W_{f} and the bulk diffusivity D decrease with increasing binding energy and find that the internal dynamics of such network liquids are controlled by the free sticker fraction D∝W_{f}∝e^{-0.5ɛ_{b}} rather than the effective bond lifetime. Referred to as the free-sticker-dominated diffusivity, the microscopic slowdown due to a gradual loss of the free stickers affects the viscosity of the condensates as well, with the scaling of the zero-shear viscosity η∝e^{0.5ɛ_{b}}. Therefore, the way of controlling the structure, diffusivity, and viscosity of the condensates through the binding energy can be tested experimentally.