Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer

The aberrant activation of STAT3 is associated with the etiology and progression in a variety of malignant epithelial-derived tumors, including head and neck squamous cell carcinoma (HNSCC) and colorectal cancer (CRC). Due to the lack of an enzymatic catalytic site or a ligand-binding pocket, there are no small-molecule inhibitors directly targeting STAT3 that have been approved for clinical translation. Emerging proteolysis targeting chimeric (PROTAC) technology-based approach represents a potential strategy to overcome the limitations of conventional inhibitors and inhibit activation of STAT3 and downstream genes. In this study, the heterobifunctional small-molecule-based PROTACs are successfully prepared from toosendanin (TSN), with 1 portion binding to STAT3 and the other portion binding to an E3 ubiquitin ligase. The optimized lead PROTAC (TSM-1) exhibits superior selectivity, potency, and robust antitumor effects in STAT3-dependent HNSCC and CRC - especially in clinically relevant patient-derived xenografts (PDX) and patient-derived organoids (PDO). The following mechanistic investigation identifies the reduced expression of critical downstream STAT3 effectors, through which TSM-1 promotes cell cycle arrest and apoptosis in tumor cells. These findings provide the first demonstration to our knowledge of a successful PROTAC-targeting strategy in STAT3-dependent epithelial cancer

Validation of the Chinese version of the diabetes health profile to predict the impact of mobile health education on quality of life in type 2 diabetes patients

PurposeThe Diabetes Health Profile (DHP18), initially created in the United Kingdom, currently lacks a Chinese version. This study endeavors to authenticate the Chinese adaptation of the DHP18 and assess the influence of mobile health (mHealth) education intervention on the quality of life of individuals living with diabetes.Patients and methodsThe study included 470 Type 2 diabetes Mellitus (T2DM) patients (204 men, 266 women), spanning an age range of 19–79 years, with an average age of 54 ± 12.40 years. Data analysis employed Jamovie and Mplus software. Moreover, test–retest reliability was evaluated in 52 hospitalized T2DM patients through two repeated measurements taken 4 weeks apart.ResultsThe Chinese version DHP18 scale exhibited high reliability, evidenced by a Cronbach’s alpha of 0.88, and coefficient of test–retest reliability of 0.84. Individual subscales also demonstrated strong reliability, ranging from 0.76 to 0.84, with test–retest reliability spanning from 0.71 to 0.74. Confirmatory Factor Analysis (CFA) employing a three-factor structure (χ2 = 294.69, GFI = 0.92, TLI = 0.91, RMSEA = 0.05, SRMR = 0.06) validated the scale’s construct validity. Notably, there was a statistically significant difference (p < 0.05) in the quality of life between Type 2 diabetes patients using mHealth education intervention and those without mHealth education intervention. Mediation analysis revealed that Appraisal of Diabetes (ADS) and Self-Management Efficacy (SED) mediated the effects of Psychological Distress (PD) and Behavior Adherence (BA) on quality of life, both significant direct and indirect effects (p < 0.001). In addition, Dietary Abstinence (DE) displayed significant overall impact (β = −0.13, p < 0.001) and indirect influence (β = −0.10, p < 0.01) on diabetic patients’ quality of life, though lacking a significant direct effect (β = −0.03, p = 0.38).ConclusionThe Chinese version of the Diabetes Health Profile Scale meets stringent psychometric standards and stands as an appropriate measurement tool for Chinese T2DM patients, maintaining comparable results to the original scale’s structure. The mHealth education intervention yielded a notably positive impact on the quality of life among T2DM patients. Mediation analysis revealed that the three dimensions of the DHP were mediated by Appraisal of Diabetes and Diabetes Self-Management Efficacy, partially mediated by Psychological Distress and Behavior Adherence, and fully mediated by Dietary Abstinence, providing insight into the positive effects of the mHealth model on the quality of life of diabetic patients

Genome-wide identification and comprehensive analysis of tubby-like protein gene family in multiple crops

IntroductionThe highly conserved tubby-like proteins (TLPs) play key roles in animal neuronal development and plant growth. The abiotic stress tolerance function of TLPs has been widely explored in plants, however, little is known about comparative studies of TLPs within crops.MethodsBioinformatic identification, phylogenetic analysis, Cis-element analysis, expression analysis, Cis-element analysis, expression analysis and so on were explored to analysis the TLP gene family of multiple crops.ResultsIn this study, a comprehensive analysis of TLP genes were carried out in seven crops to explore whether similar function of TLPs in rice could be achieved in other crops. We identified 20, 9, 14, 11, 12, 35, 14 and 13 TLP genes in Glycine max, Hordeum vulgare, Sorghum bicolor, Arabidopsis thaliana, Oryza sativa Japonica, Triticum aestivum, Setaria italic and Zea mays, respectively. All of them were divided into two groups and ten orthogroups (Ors) based on amino acids. A majority of TLP genes had two domains, tubby-like domain and F-box domain, while members of Or5 only had tubby-like domain. In addition, Or5 had more exons and shorter DNA sequences, showing that characteristics of different Ors reflected the differentiated function and feature of TLP genes in evolutionary process, and Or5 was the most different from the other Ors. Besides, we recognized 25 cis-elements in the promoter of TLP genes and explored multiple new regulation pathway of TLPs including light and hormone response. The bioinformatic and transcriptomic analysis implied the stresses induced expression and possible functional redundancy of TLP genes. We detected the expression level of 6 OsTLP genes at 1 to 6 days after seed germination in rice, and the most obvious changes in these days were appeared in OsTLP10 and OsTLP12.DiscussionCombined yeast two-hybrid system and pull down assay, we suggested that the TLP genes of Or1 may have similar function during seed germination in different species. In general, the results of comprehensive analysis of TLP gene family in multiple species provide valuable evolutionary and functional information of TLP gene family which are useful for further application and study of TLP genes

Octadecyltrimethoxysilane functionalized ZnO nanorods as a novel coating for solid-phase microextraction with strong hydrophobic surface

National Natural Scientific Foundation of China [21105123, 21105084]; Science and Technology Projects of Fujian Province [2011Y0007]; Shandong Young Scientist Awards [BS2012CL037]In this paper, we have, for the first time, proposed an approach by combining self-assembled monolayers (SAMs) and nanomaterials (NMs) for the preparation of novel solid-phase microextraction (SPME) coatings. The self-assembly of octadecyltrimethoxysilane (OTMS) on the surface of ZnO nanorods (ZNRs) was selected as a model system to demonstrate the feasibility of this approach. The functionalization of OTMS on the surface of ZNRs was characterized and confirmed using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). The OTMS-ZNRs coated fiber exhibited stronger hydrophobicity after functionalization, and its extraction efficiency for non-polar benzene homologues was increased by a factor of 1.5-3.6 when compared to a ZNRs fiber with almost identical thickness and facade. In contrast, the extraction efficiency of the OTMS-ZNRs coated fiber for polar aldehydes was 1.6-4.0-fold lower than that of the ZNRs coated fiber, further indicating its enhanced surface hydrophobicity. The OTMS-ZNRs coated fiber revealed a much higher capacity upon increasing the OTMS layer thickness to 5 mm, leading to a factor of 12.0-13.4 and 1.8-2.5 increase in extraction efficiency for the benzene homologues relative to a ZNRs coated fiber and a commercial PDMS fiber, respectively. The developed HS-SPME-GC method using the OTMS-ZNRs coated fiber was successfully applied to the determination of the benzene homologues in limnetic water samples with recovery ranging from 83 to 113% and relative standard deviations (RSDs) of less than 8%

Development of New Coatings for Solid Phase Microextraction

As a kind of sampling preparation method, solid phase microextraction (SPME) has many advantages such as simplicity, versatility, sensitivity and solvent free. It has gained widespread acceptance in separation and analysis. As the key factor of the SPME technique, coatings on SPME fiber determine the performance and application of SPME technique. Consequently, developing new coatings is the most important work for SPME. With the development of preparation methods of SPME coatings, many new coatings have appeared in recent years, and these new coatings expand the application fields of SPME technique. This review summaries the development of new SPME coatings in the past three years, and mainly focuses on the preparation methods and properties of new SPME coatings

One-Pot Visual Detection of African Swine Fever Virus Using CRISPR-Cas12a

African swine fever virus (ASFV) is a leading cause of worldwide agricultural loss. ASFV is a highly contagious and lethal disease for both domestic and wild pigs, which has brought enormous economic losses to a number of countries. Conventional methods, such as general polymerase chain reaction and isothermal amplification, are time-consuming, instrument-dependent, and unsatisfactorily accurate. Therefore, rapid, sensitive, and field-deployable detection of ASFV is important for disease surveillance and control. Herein, we created a one-pot visual detection system for ASFV with CRISPR/Cas12a technology combined with LAMP or RPA. A mineral oil sealing strategy was adopted to mitigate sample cross-contamination between parallel vials during high-throughput testing. Furthermore, the blue fluorescence signal produced by ssDNA reporter could be observed by the naked eye without any dedicated instrument. For CRISPR-RPA system, detection could be completed within 40 min with advantageous sensitivity. While CRISPR-LAMP system could complete it within 60 min with a high sensitivity of 5.8 × 102 copies/μl. Furthermore, we verified such detection platforms display no cross-reactivity with other porcine DNA or RNA viruses. Both CRISPR-RPA and CRISPR-LAMP systems permit highly rapid, sensitive, specific, and low-cost Cas12a-mediated visual diagnostic of ASFV for point-of-care testing (POCT) applications

NBR/CR‐Based High‐Damping Rubber Composites Containing Multiscale Structures for Tailoring Sound Insulation

Abstract High‐damping acoustic composites with unique sound insulation feature is reported, demonstrating surprisingly stable soundproof properties over a wide bandwidth of frequency (63–6300 Hz) with good mechanical properties. The extraordinary acoustic properties are attributed to the multiscale synergy of lamellar and hollow structures by multifillers adding. The acoustic composites are designed and fabricated through a low‐temperature one‐time rubber mixing process using nitrile butadiene rubber(NBR), chloroprene rubber (CR) as matrix and mica powder (MP), hollow glass beads (HGB), and montmorillonite (MMT) as multifillers. The soundproof mechanism is discussed in detail. Results indicate that the synergism of damping and sound absorption behaviors in the composition has a considerable impact on the acoustic characteristics, which can be controlled by the blending ratio of NBR/CR matrixes and the multiscale structures of MP/HGB/MMT multifillers. The designed multifillers acoustic composites can adapt to broadband engineering noise control including walls in express train constructions, panels of vessel or aircraft cabins, and large transportation pipelines

Application, knowledge and training needs regarding comprehensive geriatric assessment among geriatric practitioners in healthcare institutions: a cross-sectional study

Abstract Background This study aimed to investigate the actual application, knowledge, and training needs of comprehensive geriatric assessment (CGA) among geriatric practitioners in China. Methods A total of 225 geriatric practitioners attending the geriatric medicine or geriatric nursing training were recruited for this cross-sectional study. The questionnaire included demographics, healthcare institution characteristics, the actual application, knowledge, training needs, and barriers to CGA and geriatric syndromes (GS). Results Physicians and nurses were 57.3% and 42.7%, respectively. 71.1% were female, with a median age was 35 years. Almost two-thirds (140/225) of geriatric practitioners reported exposure to CGA in their clinical practice. The top five CGA evaluation items currently used were malnutrition risk (49.8%), fall risk (49.8%), activity of daily living (48.0%), pain (44.4%), and cognitive function (42.7%). Median knowledge scores for the management procedures of GS ranged from 2 to 6. Physicians identified medical insurance payment issues (29.5%) and a lack of systematic specialist knowledge and technology (21.7%) as the two biggest barriers to practicing geriatrics. Nurses cited a lack of systematic specialist knowledge and technology (52.1%) as the primary barrier. In addition, physicians and nurses exhibited significant differences in their knowledge of CGA-specific evaluation items and management procedures for GS (all P < 0.05). However, there were no significant differences in their training needs, except for polypharmacy. Conclusions The rate of CGA application at the individual level, as well as the overall knowledge among geriatric practitioners, was not adequate. Geriatric education and continuous training should be tailored to address the specific roles of physicians and nurses, as well as the practical knowledge reserves, barriers, and training needs they face