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Background The prevalence of inflammatory bowel disease (IBD) increases annually in China. The integrated traditional Chinese and western medicine is helpful to alleviate and control symptoms of IBD. Quality of life (QoL) is an important index to evaluate the clinical efficacy of IBD. However, there are few studies about IBD patient-reported outcomes (PROs) based on TCM theories. Objective To determine the framework and items, and then use them to develop the IBD PROs scale using TCM theories. Methods Under the guidance of the TCM theory of "body and mind harmony, and man's adaptation to his total environment" , literature review, core-group discussion and expert consultation were carried out. The conceptual framework and item pool of the draft of an IBD PROs scale were developed, then the corresponding items were determined, forming the draft of the IBD PROs scale. Then the draft scale was pre-tested in IBD patients treated in Department of Spleen and Stomach Diseases, the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January to June 2021. The dispersion tendency, Cronbach's α and correlation analysis were used for further item selection. Results The final IBD PROs scale is composed of two domains: body and mind harmony (12 body-related items, and 9 mind-related items) and man's adaptation to his total environment (6 items) . Conclusion The IBD PROs scale developed based on theories of TCM could be used to evaluate the QoL of IBD patients. But further clinical research is still needed to verify its reliability and validity.

Drug resistance after long‐term use of Tyrosine kinase inhibitors (TKIs) has become an obstacle for prolonging the survival time of patients with clear cell renal cell carcinoma (ccRCC). Here, genome‐wide CRISPR‐based screening to reveal that HDAC8 is involved in decreasing the sensitivity of ccRCC cells to sunitinib is applied. Mechanically, HDAC8 deacetylated ETS1 at the K245 site to promote the interaction between ETS1 and HIF‐2α and enhance the transcriptional activity of the ETS1/HIF‐2α complex. However, the antitumor effect of inhibiting HDAC8 on sensitized TKI is not very satisfactory. Subsequently, inhibition of HDAC8 increased the expression of NEK1, and up‐regulated NEK1 phosphorylated ETS1 at the T241 site to promote the interaction between ETS1 and HIF‐2α by impeded acetylation at ETS1‐K245 site is showed. Moreover, TKI treatment increased the expression of HDAC8 by inhibiting STAT3 phosphorylation in ccRCC cells is also found. These 2 findings highlight a potential mechanism of acquired resistance to TKIs and HDAC8 inhibitors in ccRCC. Finally, HDAC8‐in‐PROTACs to optimize the effects of HDAC8 inhibitors through degrading HDAC8 and overcoming the resistance of ccRCC to TKIs are synthesized. Collectively, the results revealed HDAC8 as a potential therapeutic candidate for resistance to ccRCC‐targeted therapies. [ABSTRACT FROM AUTHOR]

The current rehabilitation evaluation methods for patients with hand dysfunction face issues such as inconsistent standards and incomplete quantification processes. To address these challenges, this paper introduces a rehabilitation evaluation system that integrates various rehabilitation training modes and leverages an exoskeleton finger rehabilitation robot. This system is carefully designed and thoroughly analyzed based on the diverse training modes offered by the rehabilitation robot. Twenty stroke patients and six healthy subjects were recruited to perform grasping of static objects and gesture movement experiments, which were evaluated by Brunnstrom's motor evaluation and rehabilitation evaluation tests, respectively, and the results were compared. The experimental results showed that the results of the robotic rehabilitation evaluation of the 20 patients were consistent with the clinical Brunnstrom motor grades, which verified the accuracy of the rehabilitation evaluation system that was designed in this study. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the seasonal effects of constructed wetlands on water quality characteristics in a gate dam lake. The research reveals pronounced seasonal changes in the lake's water environment index. During winter, nitrate nitrogen and BOD5 interact significantly, jointly becoming the primary factors restricting lake water quality. In summer, the constructed wetlands effectively improve TN levels. Furthermore, water depth plays a regulatory role in Chl-a content, ammonia–nitrogen, and nitrite–nitrogen by influencing light penetration and water temperature. Urban lakes commonly suffer from nutrient over-enrichment, resulting in water quality deterioration and eutrophication. Constructed wetlands are widely employed for ecological restoration in such lakes but their efficacy in water purification noticeably fluctuates with the seasons. This study takes the constructed wetland of Jinshan Lake as an example. By analyzing the water quality parameters at three depths during both summer and winter, this study explores the influence of the constructed wetland on the water quality of each layer during different seasons and elucidates the potential mechanisms underlying these seasonal effects. The results indicate that the constructed wetland significantly enhances total nitrogen (TN) concentration during summer and exhibits the capacity for nitrate–nitrogen removal in winter. However, its efficacy in removing total phosphorus (TP) is limited, and may even serve as a potential phosphorus (P) source for the lake during winter. Water quality test results of different samples indicated they belong to Class III or IV. Restrictive factors varied across seasons: nitrate–nitrogen and BOD5 jointly affected water quality in winter, whereas TP predominantly constrained water quality in summer. These results could provide a reference for water quality monitoring and management strategies of constructed wetlands in different seasons in Jiangsu Province. [ABSTRACT FROM AUTHOR]

BACKGROUND:Post-infarction cardiovascular remodeling and heart failure are the leading cause of myocardial infarction (MI)-driven death during the past decades. Experimental observations have involved intestinal microbiota in the susceptibility to MI in mice; however, in humans, identifying whether translocation of gut bacteria to systemic circulation contributes to cardiovascular events post-MI remains a major challenge. RESULTS:Here, we carried out a metagenomic analysis to characterize the systemic bacteria in a cohort of 49 healthy control individuals, 50 stable coronary heart disease (CHD) subjects, and 100 ST-segment elevation myocardial infarction (STEMI) patients. We report for the first time higher microbial richness and diversity in the systemic microbiome of STEMI patients. More than 12% of post-STEMI blood bacteria were dominated by intestinal microbiota (Lactobacillus, Bacteroides, and Streptococcus). The significantly increased product of gut bacterial translocation (LPS and D-lactate) was correlated with systemic inflammation and predicted adverse cardiovascular events. Following experimental MI, compromised left ventricle (LV) function and intestinal hypoperfusion drove gut permeability elevation through tight junction protein suppression and intestinal mucosal injury. Upon abrogation of gut bacterial translocation by antibiotic treatment, both systemic inflammation and cardiomyocyte injury in MI mice were alleviated. CONCLUSIONS:Our results provide the first evidence that cardiovascular outcomes post-MI are driven by intestinal microbiota translocation into systemic circulation. New therapeutic strategies targeting to protect the gut barrier and eliminate gut bacteria translocation may reduce or even prevent cardiovascular events post-MI.

Persistent, high-risk human papillomavirus (HPV) infection is the primary cause of cervical cancer. Neutralizing antibodies elicited by L1-only virus-like particles (VLPs) can block HPV infection; however, the lack of high-resolution structures has limited our understanding of the mode of virus infection and the requirement for type specificity at the molecular level. Here, we describe two antibodies, A12A3 and 28F10, that specifically bind to and neutralize HPV58 and HPV59, respectively, through two distinct binding stoichiometries. We show that the epitopes of A12A3 are clustered in the DE loops of two adjacent HPV58 L1 monomers, whereas 28F10 recognizes the HPV59 FG loop of a single monomer. Via structure-based mutagenesis and analysis of antibody binding, we further identified the residues HPV58 D154, S168, and N170 and HPV59 M267, Q270, E273, Y276, K278, and R283, which play critical roles in virus infection. By substituting these strategic epitope residues into other HPV genotypes, we could then redirect the type-specific binding of the antibodies to these genotypes, thus highlighting the importance of these specific residues, HPV58 R161, S168, and N308 and HPV59 Q270, E273, and D281. Overall, our findings provide molecular insights into potential structural determinants of HPV required for infectivity and type specificity.IMPORTANCE High-risk human papillomaviruses (HPVs) are considered the major causative pathogens of cancers that affect epithelial mucosa, such as cervical cancer. However, because of the lack of high-resolution structural information on the sites of neutralization, we have yet to determine the precise mode of HPV infection and how different types of HPV cause infection. Our crystal structures in this study have uncovered discrete binding stoichiometries for two different antibodies. We show that one A12A3 Fab binds to the center of one HPV58 pentamer, whereas five 28F10 Fabs bind along the top fringe of one HPV59 pentamer. Furthermore, through targeted epitope analysis, we show that 6 to 7 discontinuous residues of the L1 major capsid protein of HPV are determinants, at least in part, for virus infection and type specificity. This knowledge will help us to unravel the process of HPV infection and can potentially be used to drive the development of therapeutics that target neutralization-sensitive sites.

CoCrFeNiZr0.3 is a two-phase coexisting (Laves + FCC) high-entropy alloy with high strength, excellent corrosion resistance, and thermal stability. However, the inhomogeneous distribution of the eutectic structure among the dendrites has a detrimental effect on the coordinated deformation of the material. The current study shows that the grain size, weave structure, and second phase distribution of high-entropy alloys can be significantly changed by thermal deformation, which affects the mechanical and physical properties, as well as the chemical stability of the alloys. In this study, the thermal deformation behavior of CoCrFeNiZr0.3 biphasic hypoeutectic high-entropy alloy was investigated using a Gleeble-3500 thermal simulation tester under the conditions of deformation temperature of 950–1100 °C and deformation rate of 0.001–1 s−1. The results show that CoCrFeNiZr0.3 high-entropy alloy has higher deformation activation energy, which means its deformation resistance is larger. In addition, the microstructure with finer grain size and uniform distribution of Laves phase can be obtained by EBSD analysis after compression at 1000 °C and 0.01 s−1. [ABSTRACT FROM AUTHOR]