Gene mutations in newly diagnosed multiple myeloma patients detected by next-generation sequencing technology.

Background: Multiple myeloma (MM) is a heterogeneous plasma-derived hematopoietic malignancy with complex genetic mutation contributing to the pathogenesis. Though gene sequencing has been applied in MM, genetic features from Chinese MM patients are reported less. We investigated the genetic mutation of newly diagnosed multiple myeloma (NDMM) patients and explore its correlation with cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH). Methods: A total of 206 patients with NDMM were enrolled. After enriching plasma cells with CD138 magnetic beads, 92 MM-related target gene mutations were detected by the Illumina sequencing platform, and six common genetic abnormalities were detected by FISH. Results: 162 cases (78.6%) had at least one gene mutation detected by NDMM. The top 5 mutated genes were KRAS, NRAS, TRAF3, BRAF, and TP53. Cytogenetic abnormalities detected by FISH have a certain correlation with gene mutations, t(11;14) translocations are often accompanied by CCND1 and TP53 mutations, KLHL6 in t(4;14), SP140, CDKN1B and PRKD2 in t(14;16) and t(14;20) translocations. The mutation ratio was higher for EGR1, while lower of CCND1 in patients with gain 1q21. The TP53 mutation was more likely in patients with 17p deletion. The gene mutation affects the pathway of the RNA process is more frequently occurring in males and age less than 70 years patients. The International Staging System (ISS) Stage III correlated with gene mutations in the NK-κB pathway while Revised ISS (R-ISS) Stage III correlated with the DNA damage repair pathway. Conclusions: There are various gene mutations in NDMM patients, mainly RAS/MAPK and NF-κB pathway gene pathways.

Effects of debranched starch on physicochemical properties and in vitro digestibility of flat rice noodles.

Aiming to develop flat rice noodles with both desirable textural quality and lower starch digestibility, we investigated the effect of adding indica rice debranched starch (RDBS) on the quality of flat rice noodles. In this study, adding RDBS to flat rice noodles enhanced their mechanical properties. Cooking characteristic analysis showed that incorporating RDBS into dried flat rice noodles increased the rehydration ratio by 16.1 % and reduced rehydration time by 26.5 %. Scanning electron microscopy (SEM) revealed the presence of microparticles formed through the self-assembly of RDBS within the network of flat rice noodles. X-ray diffraction (XRD) analysis demonstrated that the addition of RDBS elevated the crystallinity of the flat rice noodles, rising from 9.59 % to 22.57 %. In addition, the in vitro simulated digestion test suggested the addition of RDBS led to a threefold increase in the content of slowly digestible starch (SDS) and a ninefold increase in resistant starch (RS) content in flat rice noodles. This study found that adding RDBS into flat rice noodles can effectively reduce their digestion rate and improve their eating quality. It could be a promising approach for creating functional rice noodles aimed at alleviating public health concerns such as diabetes and obesity.

Leap-Type Response of Redox/Photo-Active Lanthanide-Based Metal-Organic Frameworks for Early and Accurate Screening of Prostate Cancer.

The development of high-accuracy technologies to distinguish the quite tiny concentration change of tumor markers between negative and positive is of vital significance for early screening and diagnosis of cancers, but is still a great challenge for the conventional biosensors because of their "gradual" detection mode. Herein, a unique "leap-type" responsive lanthanide MOF-based biosensor (designated as Tb-CeMOF-X) with defect-mediated redox-/photo-activities is developed for precisely identifying acid phosphatase (ACP), an early pathological marker of prostate cancer (PCa) in serum. The engineered Tb-CeMOF-X probe achieves a bursting switch-on luminescence at the critical concentration of ACP (9 U·L-1), while keeping silent below this threshold, undergoing a qualitative signal change from "zero" to "one" between negative and positive indicators and thus significantly improving the identification precision. Significantly, such "leap-type" response performance can be further edited and amplified by rational defect engineering in the crystal structure to improve the accessibility of active centers, consequently maximizing the detection sensitivity toward ACP in the complex biological media. This study proposes the first paradigm for the development of "leap-type" biosensors with ultra-sensitive differentiation capability between negative and positive, and provides a potentially valuable tool for early and accurate screening of PCa.

Transcriptional landscape of a hypoxia response identifies cell-specific pathways for adaptation.

How the HIF-1 (Hypoxia-Inducible) transcription factor drives and coordinates distinct responses to low oxygen across diverse cell types is poorly understood. We present a multi-tissue single-cell gene-expression atlas of the hypoxia response of the nematode Caenorhabditis elegans . This atlas highlights how cell-type-specific HIF-1 responses overlap and diverge among and within neuronal, intestinal, and muscle tissues. Using the atlas to guide functional analyses of candidate muscle-specific HIF-1 effectors, we discovered that HIF-1 activation drives downregulation of the tspo-1 ( TSPO, Translocator Protein) gene in vulval muscle cells to modulate a hypoxia-driven change in locomotion caused by contraction of body-wall muscle cells. We further showed that in human cardiomyocytes HIF-1 activation decreases levels of TSPO and thereby alters intracellular cholesterol transport and the mitochondrial network. We suggest that TSPO-1 is an evolutionarily conserved mediator of HIF-1-dependent modulation of muscle and conclude that our gene-expression atlas can help reveal how HIF-1 drives cell-specific adaptations to hypoxia.

High-throughput volumetric mapping of synaptic transmission.

Volumetric imaging of synaptic transmission in vivo requires high spatial and high temporal resolution. Shaping the wavefront of two-photon fluorescence excitation light, we developed Bessel-droplet foci for high-contrast and high-resolution volumetric imaging of synapses. Applying our method to imaging glutamate release, we demonstrated high-throughput mapping of excitatory inputs at >1,000 synapses per volume and >500 dendritic spines per neuron in vivo and unveiled previously unseen features of functional synaptic organization in the mouse primary visual cortex.

A short linear glucan nanocomposite hydrogel formed by in situ self-assembly with highly elastic, fatigue-resistant and self-recovery.

Polyacrylamide (PAM) hydrogels are widely used in wide-ranging applications in biology, medicine, pharmaceuticals and environmental sectors. However, achieving the requisite mechanical properties, fatigue resistance, self-recovery, biocompatibility, and biodegradability remains a challenge. Herein, we present a facile method to construct a nanocomposite hydrogel by integrating short linear glucan (SLG), obtained by debranching waxy corn starch, into a PAM network through self-assembly. The resulting composite hydrogel with 10 % SLG content exhibited satisfactory stretchability (withstanding over 1200 % strain), along with maximum compressive and shear strengths of about 490 kPa and 39 kPa at 90 % deformation, respectively. The hydrogel demonstrated remarkable resilience and could endure repeated compression and stretching. Notably, the nanocomposite hydrogel with 10 % SLG content exhibited full stress recovery at 90 % compression deformation after 20 s, without requiring specific environmental conditions, achieving an energy dissipation recovery rate of 98 %. Meanwhile, these hydrogels exhibited strong adhesion to various soft and hard substrates, including skin, glasses and metals. Furthermore, they maintain solid integrity at both 37 °C and 50 °C after swelling equilibrium, unlike traditional PAM hydrogels, which exhibited softening under similar conditions. We hope that this PAM-SLG hydrogel will open up new avenues for the development of multifunctional electronic devices, offering enhanced performance and versatility.

Design and Characterization of a Novel Core-Shell Nano Delivery System Based on Zein and Carboxymethylated Short-Chain Amylose for Encapsulation of Curcumin.

Curcumin is a naturally occurring hydrophobic polyphenolic compound with a rapid metabolism, poor absorption, and low stability, which severely limits its bioavailability. Here, we employed a starch-protein-based nanoparticle approach to improve the curcumin bioavailability. This study focused on synthesizing nanoparticles with a zein "core" and a carboxymethylated short-chain amylose (CSA) "shell" through anti-solvent precipitation for delivering curcumin. The zein@CSA core-shell nanoparticles were extensively characterized for physicochemical properties, structural integrity, ionic stability, in vitro digestibility, and antioxidant activity. Fourier-transform infrared (FTIR) spectroscopy indicates nanoparticle formation through hydrogen-bonding, hydrophobic, and electrostatic interactions between zein and CSA. Zein@CSA core-shell nanoparticles exhibited enhanced stability in NaCl solution. At a zein-to-CSA ratio of 1:1.25, only 15.7% curcumin was released after 90 min of gastric digestion, and 66% was released in the intestine after 240 min, demonstrating a notable sustained release effect. Furthermore, these nanoparticles increased the scavenging capacity of the 1,1-diphenyl-2-picrylhydrazyl (DPPH•) free radical compared to those composed solely of zein and were essentially nontoxic to Caco-2 cells. This research offers valuable insights into curcumin encapsulation and delivery using zein@CSA core-shell nanoparticles.

Different effects of pea protein on the properties and structures of starch gel at low and high solid concentrations.

In the context of starch-protein composite gels, the influence of protein on gel formation significantly shapes the textural attributes of starch gels, leading to distinct outcomes. This study aimed to evaluate how different ratios of pea protein (PP) affect the properties and structures of starch-protein composite gels at low (10 wt%) and high (40 wt%) solid concentrations. The addition of PP had opposite effects on the two gels. Compared to the pure starch gel, the low-concentration composite gel (LCG) with 20 % PP experienced a 48.90 ± 0.33 % reduction in hardness, and the storage modulus (G') decreased from 14,100 Pa to 5250 Pa, indicating a softening effect of PP on LCG. Conversely, the hardness of the high-concentration composite gel (HCG) with 20 % PP exhibited a 62.19 ± 0.03 % increase in hardness, and G' increased from 12,100 Pa to 41,700 Pa, highlighting the enhancing effect of PP on HCG. SEM and fluorescence microscopy images showed that PP induced uneven network sizes in LCG, while HCG with a PP content of 20 %, PP, together with starch, formed a three-dimensional network. This study provides valuable insights and guidance for the design and production of protein-enriched starch gel products with different textural properties.

Evaluation of a miniature mass spectrometer based point-of-care-test method for direct analysis of amlodipine and benazepril in whole blood.

A miniature mass spectrometer (mMS) based point-of-care testing (POCT) method was evaluated for on-site detecting the hypertension drugs, amlodipine and benazepril. The instrument parameters, including voltage, ISO1, ISO2, and CID, were optimized, under which the target compounds could be well detected in MS2. When these two drugs were injected simultaneously, the mutual ionization inhibition and mutual reduction between amlodipine and benazepril were evaluated. This phenomenon was severe on the precursor ions but had a small impact on the product ions, thus making this POCT method suitable for analysis using product ions. Finally, the method was validated and applied. The blood samples from patients were tested one hour after oral administration of the drugs (20 mg), and the benazepril was quantitatively analyzed using a standard curve, with detected concentrations ranging from 190.6 to 210 µg L-1 and a relative standard deviation (RSD) of 8.6 %. In summary, amlodipine has low sensitivity and can only be detected at higher concentrations, while benazepril has high sensitivity, good linearity, and even meets semi-quantitative requirements. The research results of this study are of great clinical significance for monitoring blood drug concentrations during hypertension medication, predicting drug efficacy, and customizing individualized medication plans.

Adaptive optical third-harmonic generation microscopy for in vivo imaging of tissues.

Third-harmonic generation microscopy is a powerful label-free nonlinear imaging technique, providing essential information about structural characteristics of cells and tissues without requiring external labelling agents. In this work, we integrated a recently developed compact adaptive optics module into a third-harmonic generation microscope, to measure and correct for optical aberrations in complex tissues. Taking advantage of the high sensitivity of the third-harmonic generation process to material interfaces and thin membranes, along with the 1,300-nm excitation wavelength used here, our adaptive optical third-harmonic generation microscope enabled high-resolution in vivo imaging within highly scattering biological model systems. Examples include imaging of myelinated axons and vascular structures within the mouse spinal cord and deep cortical layers of the mouse brain, along with imaging of key anatomical features in the roots of the model plant Brachypodium distachyon. In all instances, aberration correction led to significant enhancements in image quality.

The Construction of Sodium Alginate/Carboxymethyl Chitosan Microcapsules as the Physical Barrier to Reduce Corn Starch Digestion.

To enhance the resistant starch (RS) content of corn starch, in this work, carboxymethyl chitosan/corn starch/sodium alginate microcapsules (CMCS/CS/SA) with varying concentrations of SA in a citric acid (CA) solution were designed. As the SA concentration increased from 0.5% to 2%, the swelling of the CMCS/CS/SA microcapsule decreased from 15.28 ± 0.21 g/g to 3.76 ± 0.66 g/g at 95 °C. Comparatively, the onset, peak, and conclusion temperatures (To, Tp, and Tc) of CMCS/CS/SA microcapsules were higher than those of unencapsulated CS, indicating that the dense network structure of microcapsules reduced the contact area between starch granules and water, thereby improving thermal stability. With increasing SA concentration, the intact and dense network of CMCS/CS/SA microcapsules remained less damaged after 120 min of digestion, suggesting that the microcapsules with a high SA concentration provided better protection to starch, thereby reducing amylase digestibility. Moreover, as the SA concentration increased from 0.5% to 2%, the RS content of the microcapsules during in vitro digestion rose from 42.37 ± 0.07% to 57.65 ± 0.45%, attributed to the blocking effect of the microcapsule shell on amylase activity. This study offers innovative insights and strategies to develop functional starch with glycemic control properties, holding significant scientific and practical value in preventing diseases associated with abnormal glucose metabolism.

Evaluation of the Effectiveness of Children's Dental Care Programs: A Retrospective Study.

This study aimed to evaluate the long-term impact of children's dental care programs on children and adolescents to reduce oral health inequalities. It measured and assessed the improvement effects of children's dental care programs on the oral health of children and adolescents as part of the efforts to decrease oral health disparities in this age group. It included 406 individuals who participated in student and children's dental care program between 2013 and 2019 at screening facilities in Gwangjin-gu, Seoul. A frequency analysis was conducted for demographic characteristics, and a binary logistic regression analysis was performed to identify factors influencing the prevalence of dental caries as the dependent variable. The data were analyzed using PASW Statistics with the statistical significance level set at α = 0.05. Regarding oral health status based on the frequency of participation in children's dental care program for children and adolescents, participants with seven or more sessions had lower prevalence rates of dental caries, malocclusion, and periodontal disease than those with only one session. Second, when comparing oral health status in children's dental care program between primary and adolescent age groups, individuals under continuous oral health care showed a decrease in permanent teeth affected by dental caries, dental caries prevalence, and malocclusion prevalence (excluding primary school age). Third, a binary logistic regression analysis revealed significant influences (p < 0.05) of the developmental stage and frequency of program participation on dental caries prevalence. Children's dental care programs are essential for alleviating oral health inequalities among children and adolescents and preventing oral diseases. Furthermore, the developmental stage of children and the frequency of program participation are crucial factors in preventing oral conditions, such as dental caries.

Robust Thiazole-Linked Covalent Organic Frameworks for Water Sensing with High Selectivity and Sensitivity.

The rational design of covalent organic frameworks (COFs) with hydrochromic properties is of significant value because of the facile and rapid detection of water in diverse fields. In this report, we present a thiazole-linked COF (TZ-COF-6) sensor with a large surface area, ultrahigh stability, and excellent crystallinity. The sensor was synthesized through a simple three-component reaction involving amine, aldehyde, and sulfur. The thiazole and methoxy groups confer strong basicity to TZ-COF-6 at the nitrogen sites, making them easily protonated reversibly by water. Therefore, TZ-COF-6 displayed color change visible to the naked eye from yellow to red when protonated, along with a red shift in absorption in the ultraviolet-visible diffuse reflectance spectra (UV-vis DRS) when exposed to water. Importantly, the water-sensing process was not affected by polar organic solvents, demonstrating greater selectivity and sensitivity compared to other COF sensors. Therefore, TZ-COF-6 was used to detect trace amounts of water in organic solvents. In strong polar solvents, such as N,N-dimethyl formamide (DMF) and ethanol (EtOH), the limit of detection (LOD) for water was as low as 0.06% and 0.53%, respectively. Even after 8 months of storage and 15 cycles, TZ-COF-6 retained its original crystallinity and detection efficiency, displaying high stability and excellent cycle performance.

Validation of the modified CT criteria for identifying non-adenomas.

PURPOSE: Although adrenal computed tomography (CT) percentage washout is a potentially powerful imaging technique for differentiating adrenal adenomas from non-adenomas, its application to non-adenomas can be problematic. Recently, modified criteria for diagnosing pheochromocytomas using adrenal CT were developed based on data from 199 patients with surgically proven pheochromocytomas and adenomas. However, these criteria have not been thoroughly validated. The purpose of this study was to validate the performance of the modified criteria for diagnosing non-adenomas including pheochromocytomas. METHODS: The conventional and modified criteria were applied to 266 patients from two cohorts who had surgically proven lipid-poor adenomas (155/266, 58.3%) and non-adenomas (111/266, 41.7%) and underwent adrenal CT. Two radiologists calculated the attenuation on each dynamic phase and percentage washout of adrenal masses. The final assessments based on the conventional and modified criteria were categorized into adenomas or non-adenomas. The diagnostic performance of each criterion for diagnosing non-adenomas was evaluated using the area under the receiver operating characteristic curve (AUC). False negatives and positives were also compared. RESULTS: The AUC for the diagnosis of non-adenomas was 0.806 for conventional criteria and 0.858 for modified criteria (p = 0.047). The false-negative rate of conventional criteria for the diagnosis of non-adenomas was 29.7%. Use of modified criteria could have reduced the false-negative rate by to 7.2%. The false-positive rate increased from 9% to 21.3% when using the modified criteria. CONCLUSION: The utilization of modified criteria has the potential to identify additional non-adenomas that would otherwise be misdiagnosed as adenomas using conventional criteria alone.

Utilization of heat-induced curdlan gel to improve the cooking qualities of thermally sterilized fresh rice noodles.

Thermal sterilization is the most economical and efficient method to guarantee the shelf life of extruded fresh rice noodles, but it often leads to a high cooking breakage rate and poor elongation at break of the noodles. The aim of this study was to improve the edible quality of sterilized fresh rice noodles through the addition of low concentrations of curdlan (0.38 %-1.13 %), which can form a thermal-irreversible gel to resist high-temperature sterilization. Compared with the control group without curdlan, the cooking breakage rate of sterilized fresh rice noodles with 1.13 % curdlan decreased from 16.85 % to 5.22 %, the tensile strain increased from 91.15 % to 147.05 %, and the microstructure was more dense and uniform. The results showed that adding the proper amount of curdlan is an effective strategy to improve the quality of sterilized fresh rice noodles.

Reducing Cholesterol Level in Live Macrophages Improves Delivery Performance by Enhancing Blood Shear Stress Adaptation.

In recent years, live-cell-based drug delivery systems have gained considerable attention. However, shear stress, which accompanies blood flow, may cause cell death and weaken the delivery performance. In this study, we found that reducing cholesterol in macrophage plasma membranes enhanced their tumor targeting ability by more than 2-fold. Our study demonstrates that the reduced cholesterol level deactivated the mammalian target of rapamycin (mTOR) and consequently promoted the nuclear translocation of transcription factor EB (TFEB), which in turn enhanced the expression of superoxide dismutase (SOD) to reduce reactive oxygen species (ROS) induced by shear stress. A proof-of-concept system using low cholesterol macrophages attached to MXene (e.g., l-RX) was fabricated. In a melanoma mouse model, l-RX and laser irradiation treatments eliminated tumors with no recurrences observed in mice. Therefore, cholesterol reduction is a simple and effective way to enhance the targeting performance of macrophage-based drug delivery systems.

Regulating Electron Metal-Support Interaction to Suppress N2O Formation in the Selective Catalytic Oxidation of Ammonia.

N2O is a common byproduct in the selective catalytic oxidation of ammonia, and its generation often needs to be inhibited due to its strong greenhouse effect. In this paper, using Ag/ZSO-Y as a model catalyst, the N2O selectivity was reduced by 30% through modulation of the electron metal-support interaction. The results demonstrate that the work function of the support can be regulated by the content of the doping element. As the Zr content increases in SnO2, the work function of the support decreases. Moreover, there is a positive correlation between the charge transfer amount and the work function of the support. A series of in situ DRIFTS and density functional theory calculations revealed that the -NO and -N reactions are the primary pathways for N2O formation. By adjustment of the work function of the support through varying the Zr doping level, the electronic structure of Ag NPs was further tuned, resulting in an increased reaction energy barrier for -NO and -N reactions, effectively suppressing N2O formation.

Comparison of 0.02% atropine eye drops, peripheral myopia defocus design spectacle lenses, and orthokeratology for myopia control.

CLINICAL RELEVANCE: There are many methods to control the progression of myopia. However, it is currently unknown which method could better control myopia progression: 0.02% atropine eye drops, peripheral myopic defocus design spectacle lenses (PMDSL), or orthokeratology (OK). BACKGROUND: To compare the efficacy of 0.02% atropine, PMDSL, and OK to control axial length (AL) elongation in children with myopia. METHODS: This study was analysed based on a previous cohort study (0.02% atropine group) and retrospective data (PMDSL and OK group). Overall, 387 children aged 6-14 years with myopia - 1.00D to - 6.00D in the three groups were divided into four subgroups according to age and spherical equivalent refraction (SER). The primary outcome was changed in AL over 1-year. RESULTS: The mean axial elongation was 0.30 ± 0.21 mm, 0.23 ± 0.16 mm, and 0.17 ± 0.19 mm in the 0.02% atropine, PMDSL, and OK groups, respectively. Multivariate linear regression analyses showed significant differences in axial elongation among the three groups, especially in children aged 6-10, but not in children aged 10.1-14; the corresponding axial elongation was 0.35 ± 0.21 mm, 0.23 ± 0.17 mm, and 0.21 ± 0.20 mm (P < 0.05 between any two groups, except between PMDSL and OK groups at P > 0.05) and 0.22 ± 0.20 mm, 0.21 ± 0.13 mm, and 0.13 ± 0.18 mm (P < 0.05 between any two groups, except between 0.02% atropine and PMDSL groups at P > 0.05) in children with SER from - 1.00D to - 3.00D and from - 3.01D to - 6.00D, respectively. CONCLUSIONS: Within the limits of this study design and using only the current brand of PMDSL, OK appeared to be the best method, followed by PMDSL and then 0.02% atropine, for controlling AL elongation over one year. However, different effects were found in the various age and SER subgroups.

Changes in axial length in anisometropic children wearing orthokeratology lenses.

Purpose: There is a particular anisometropia occurring in one eye with myopia, while the other eye has very low myopia, emmetropia, or very low hyperopia. It is unclear how the binocular axial length changes when these children wear unilateral OK lenses only in the more myopic eyes. This study investigates the changes in the axial elongation of both eyes. Methods: This is a 1-year retrospective study. In total, 148 children with myopic anisometropia were included. The more myopic eyes were wearing orthokeratology lenses (treated eyes), whereas the contralateral eyes were not indicated for visual correction (untreated eyes). The untreated eyes were classified into three subgroups based on the spherical equivalent refraction (SER): low myopia (≤ -0.50 D, n = 37), emmetropia (+0.49 to -0.49 D, n = 76), and low hyperopia (≥0.50 D, n = 35). Changes in the axial length (AL) were compared between the untreated and treated eyes and among the three subgroups. Results: The axial elongation was 0.14 ± 0.18 mm and 0.39 ± 0.27 mm in all treated and untreated eyes, respectively (p < 0.001). The interocular AL difference decreased significantly from 1.09 ± 0.45 mm at the baseline to 0.84 ± 0.52 mm at 1 year (p < 0.001). The baseline median (Q1, Q3) SER of the untreated eyes were -0.75 D (-0.56, -0.88 D), 0.00 D (0.00, -0.25 D), and +0.75 D (+1.00, +0.62 D) in low myopia, emmetropia, and low hyperopia subgroups, respectively. The axial elongation was 0.14 ± 0.18 mm, 0.15 ± 0.17 mm, and 0.13 ± 0.21 mm (p = 0.92) in the treated eyes and 0.44 ± 0.25 mm, 0.35 ± 0.24 mm, and 0.41 ± 0.33 mm in the untreated eyes (p = 0.11) after 1 year. Multivariate linear regression analyses only showed significant differences in axial elongation between the emmetropia and low myopia subgroups of untreated eyes (p = 0.04; p > 0.05 between other subgroups). Conclusion: Unilateral orthokeratology lenses effectively reduced axial elongation in the more myopic eyes and reduced interocular AL differences in children with myopic anisometropia. The refractive state of the untreated eyes did not affect the axial elongation of the more myopic eye wearing the orthokeratology lens. In the untreated eyes, AL increased faster in the low myopia subgroup than in the emmetropia subgroup.