Exploration of the combined role of immune checkpoints and immune cells in the diagnosis and treatment of ankylosing spondylitis: a preliminary study immune checkpoints in ankylosing spondylitis.

OBJECTIVE: Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of ankylosing spondylitis (AS) remain unclear. METHODS: Hip ligament samples were obtained from two patient groups: those with AS and femoral head deformity, and those with femoral head necrosis but without AS, undergoing hip arthroplasty. Label-Free Quantification (LFQ) Protein Park Analysis was used to identify the protein composition of the ligaments. Peripheral blood samples of 104 AS patients from public database were used to validate the expression of key proteins. KEGG, GO, and GSVA were employed to explore potential pathways regulated by immune checkpoints in AS progression. xCell was used to calculate cell infiltration levels, LASSO regression was applied to select key cells, and the correlation between immune checkpoints and immune cells was analyzed. Drug sensitivity analysis was conducted to identify potential therapeutic drugs targeting immune checkpoints in AS. The expression of key genes was validated through immunohistochemistry (IHC). RESULTS: HLA-DMB and HLA-DPA1 were downregulated in the ligaments of AS and this has been validated through peripheral blood datasets and IHC. Significant differences in expression were observed in CD8 + Tcm, CD8 + T cells, CD8 + Tem, osteoblasts, Th1 cells, and CD8 + naive T cells in AS. The infiltration levels of CD8 + Tcm and CD8 + naive T cells were significantly positively correlated with the expression levels of HLA-DMB and HLA-DPA1. Immune cell selection using LASSO regression showed good predictive ability for AS, with AUC values of 0.98, 0.81, and 0.75 for the three prediction models, respectively. Furthermore, this study found that HLA-DMB and HLA-DPA1 are involved in Th17 cell differentiation, and both Th17 cell differentiation and the NF-kappa B signaling pathway are activated in the AS group. Drug sensitivity analysis showed that AS patients are more sensitive to drugs such as doramapimod and GSK269962A. CONCLUSION: Immune checkpoints and immune cells could serve as avenues for exploring diagnostic and therapeutic strategies for AS.

Dexmedetomidine affects the NOX4/Nrf2 pathway to improve renal antioxidant capacity.

OBJECTIVES: The study aimed to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and explore the protective pathways of DEX on rat kidneys in terms of oxidative stress. METHODS: An acute restraint stress model was utilized, where rats were restrained for 3 hours after a 15-minute swim. Biochemical tests and histopathological sections were conducted to evaluate renal function, along with the measurement of oxidative stress and related pathway proteins. KEY FINDINGS: The open-field experiments validated the successful establishment of the acute stress model. Acute stress-induced renal injury led to increased NADPH oxidase 4 (NOX4) protein expression and decreased expression levels of nuclear transcription factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1). Following DEX treatment, there was a significant reduction in renal NOX4 expression. The DEX-treated group exhibited normalized renal biochemical results and less damage observed in pathological sections compared to the acute stress group. CONCLUSIONS: The findings suggest that DEX treatment during acute stress can impact the NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress, thereby preventing acute stress-induced kidney injury. Additionally, DEX shows promise for clinical applications in stress syndromes.

The AGAMOUS-LIKE 16-GENERAL REGULATORY FACTOR 1 module regulates axillary bud outgrowth via catabolism of abscisic acid in cucumber.

Lateral branches are important components of shoot architecture and directly affect crop yield and production cost. Although sporadic studies have implicated abscisic acid (ABA) biosynthesis in axillary bud outgrowth, the function of ABA catabolism and its upstream regulators in shoot branching remain elusive. Here, we showed that the MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) is a positive regulator of axillary bud outgrowth in cucumber (Cucumis sativus). Functional disruption of CsAGL16 led to reduced bud outgrowth, whereas overexpression of CsAGL16 resulted in enhanced branching. CsAGL16 directly binds to the promoter of the ABA 8'-hydroxylase gene CsCYP707A4 and promotes its expression. Loss of CsCYP707A4 function inhibited axillary bud outgrowth and increased ABA levels. Elevated expression of CsCYP707A4 or treatment with an ABA biosynthesis inhibitor largely rescued the Csagl16 mutant phenotype. Moreover, cucumber General Regulatory Factor 1 (CsGRF1) interacts with CsAGL16 and antagonizes CsAGL16-mediated CsCYP707A4 activation. Disruption of CsGRF1 resulted in elongated branches and decreased ABA levels in the axillary buds. The Csagl16 Csgrf1 double mutant exhibited a branching phenotype resembling that of the Csagl16 single mutant. Therefore, our data suggest that the CsAGL16-CsGRF1 module regulates axillary bud outgrowth via CsCYP707A4-mediated ABA catabolism in cucumber. Our findings provide a strategy to manipulate ABA levels in axillary buds during crop breeding to produce desirable branching phenotypes.

Nanostructured, Biodoping-Activated Fungi-Modified Wood for Enhanced Cd2+ Removal: Performances and Insight on Adsorption Mechanisms.

Nanostructured activated carbon (AC) adsorbents derived from woody biomass have garnered attention for their potential usage to remove toxic substances from the environment due to their high specific surface area, superior micro/mesoporosity, and tunable surface chemistry profile. However, chemical dopants widely used to enhance the chemical reactivity with heavy metals would pollute the environment and conflict with the vision of a cleaner and sustainable environment. Herein, we report a facile, green, and sustainable approach using fungi modification combined with alkali activation to produce AC for heavy metal removal. The decayed wood-derived AC (DAC) exhibited a high specific surface area of 2098 m2/g, and the content of O and N functional groups was 18 and 2.24%, respectively. It showed remarkable adsorption capacity toward Cd2+ of 148.7 mg/g, which was much higher than most reported Cd2+ adsorbents. Such excellent adsorption capacity was primarily based on enhanced physical adsorption (pore filling, π-π) and chemical adsorption (functional group complexation, ion exchange, and precipitation). Additionally, the DAC showed rapid kinetics and remarkable applicability in both dynamic environments and actual water samples. These results suggest that decayed wood has excellent potential for efficient use in the removal of Cd2+ from wastewater. Furthermore, these results indicate that decayed wood can be cleanly produced into high efficiency heavy metal adsorbents to realize value-added utilization of decayed wood.

High temperature delays and low temperature accelerates evolution of a new protein phenotype.

Since the origin of life, temperatures on earth have fluctuated both on short and long time scales. How such changes affect the rate at which Darwinian evolution can bring forth new phenotypes remains unclear. On the one hand, high temperature may accelerate phenotypic evolution because it accelerates most biological processes. On the other hand, it may slow phenotypic evolution, because proteins are usually less stable at high temperatures and therefore less evolvable. Here, to test these hypotheses experimentally, we evolved a green fluorescent protein in E. coli towards the new phenotype of yellow fluorescence at different temperatures. Yellow fluorescence evolved most slowly at high temperature and most rapidly at low temperature, in contradiction to the first hypothesis. Using high-throughput population sequencing, protein engineering, and biochemical assays, we determined that this is due to the protein-destabilizing effect of neofunctionalizing mutations. Destabilization is highly detrimental at high temperature, where neofunctionalizing mutations cannot be tolerated. Their detrimental effects can be mitigated through excess stability at low temperature, leading to accelerated adaptive evolution. By modifying protein folding stability, temperature alters the accessibility of mutational paths towards high-fitness genotypes. Our observations have broad implications for our understanding of how temperature changes affect evolutionary adaptations and innovations.

Identification of the YIPF3-YIPF4 heterodimer as a novel Golgiphagy receptor.

Golgiphagy is a selective form of macroautophagy, characterized by the targeted degradation of Golgi compartments through specific receptors. In two recent studies, the YIPF3-YIPF4 heterodimer has been independently identified as the first Golgiphagy receptor within mammalian cells. This heterodimeric complex exhibits a direct affinity for mammalian Atg8-family proteins (ATG8s), thereby facilitating the expansion of phagophores in proximity to Golgi regions. Notably, the interaction between YIPF3-YIPF4 heterodimers and ATG8s undergoes regulatory modulation through phosphorylation. Furthermore, cells lacking either YIPF3 or YIPF4 display defects in Golgiphagy. To elucidate the physiological relevance of these proteins, the necessity of YIPF3-YIPF4 in orchestrating Golgi proteome remodeling was substantiated through experimentation in an in vitro neuronal differentiation model.Abbreviation: ATG: autophagy related; ATG8s: mammalian Atg8-family proteins; LIR, LC3-interacting region.

Optimization of Diagnosis-Related Groups for 14,246 Patients with Uterine Leiomyoma in a Single Center in Western China Using a Machine Learning Model.

Background: Uterine leiomyoma (UL) is one of the most common benign tumors in women, and its incidence is gradually increasing in China. The clinical complications of UL have a negative impact on women's health, and the cost of treatment poses a significant burden on patients. Diagnosis-related groups (DRG) are internationally recognized as advanced healthcare payment management methods that can effectively reduce costs. However, there are variations in the design and grouping rules of DRG policies across different regions. Therefore, this study aims to analyze the factors influencing the hospitalization costs of patients with UL and optimize the design of DRG grouping schemes to provide insights for the development of localized DRG grouping policies. Methods: The Mann-Whitney U-test or the Kruskal-Wallis H-test was employed for univariate analysis, and multiple stepwise linear regression analysis was utilized to identify the primary influencing factors of hospitalization costs for UL. Case combination classification was conducted using the exhaustive chi-square automatic interactive detection (E-CHAID) algorithm within a decision tree framework. Results: Age, occupation, number of hospitalizations, type of medical insurance, Transfer to other departments, length of stay (LOS), type of UL, admission condition, comorbidities and complications, type of primary procedure, other types of surgical procedures, and discharge method had a significant impact on hospitalization costs (P<0.05). Among them, the type of primary procedure, other types of surgical procedures, and LOS were the main factors influencing hospitalization costs. By incorporating the type of primary procedure, other types of surgical procedures, and LOS into the decision tree model, patients were divided into 11 DRG combinations. Conclusion: Hospitalization costs for UL are mainly related to the type of primary procedure, other types of surgical procedures, and LOS. The DRG case combinations of UL based on E-CHAID algorithm are scientific and reasonable.

Constructing Matching Cathode-Anode Interphases with Improved Chemo-mechanical Stability for High-Energy Batteries.

Coupling Ni-rich layered oxide cathodes with Si-based anodes is one of the most promising strategies to realize high-energy-density Li-ion batteries. However, unstable interfaces on both cathode and anode sides cause continuous parasitic reactions, resulting in structural degradation and capacity fading of full cells. Herein, lithium tetrafluoro(oxalato) phosphate is synthesized and applied as a multifunctional electrolyte additive to mitigate irreversible volume swing of the SiOx anode and suppress undesirable interfacial evolution of the LiNi0.83Co0.12Mn0.05O2 (NCM) cathode simultaneously, resulting in improved cycle life. Benefiting from its desirable redox thermodynamics and kinetics, the molecularly tailored additive facilitates matching interphases consisting of LiF, Li3PO4, and P-containing macromolecular polymer on both the NCM cathode and SiOx anode, respectively, modulating interfacial chemo-mechanical stability as well as charge transfer kinetics. More encouragingly, the proposed strategy enables 4.4 V 21700 cylindrical batteries (5 Ah) with excellent cycling stability (92.9% capacity retention after 300 cycles) under practical conditions. The key finding points out a fresh perspective on interfacial optimization for high-energy-density battery systems.

Developing high performance biodegradable film based on crosslinking of cellulose acetate and tannin using caprolactone.

The use of metal catalysts during the production process of cellulose acetate (CA) film can have an impact on the environment, due to their toxicity. Diphenyl phosphate (DPP) was used instead of toxic metal catalyst to react with cellulose acetate, tannin (T) and caprolactone (CL) for preparation of cellulose acetate-caprolactone-tannin (CA-CL-T) film. The results show that DPP can produce a cross-linked network structure composed of tannin, caprolactone and cellulose acetate. The maximum molecular weight reached 113,260 Da. The introduction of tannin and caprolactone into cellulose acetate caused the resulting CA-CL-T film acquire excellent strengthening/toughening effect, in which a tensile strength of 23 MPa and elongation at break of 18 % were attained. More importantly, the resistance of the film to UV radiation was significantly improved with the tannin addition, which was corroborated by the CA-CL-T film still exhibiting a tensile strength of 13 MPa and elongation at break around 13 % after continuous exposure to UV radiation for 9 days. On the other hand, the insertion of caprolactone provoked enhancement of the overall moisture resistance. Five days treatment of the films with Penicillium sp. induced gradual drop in quality, indicating the CA-CL-T film show response to biodegradation. In all, the effective crosslinking between the components of the developed material is responsible for the acquired set of these distinct characteristics.

Effect of tannic/gallic acid-iron dyeing treatment on surface color and light fastness of bamboo veneer.

Currently, the quest for bamboo materials with high color fastness, rich colors and environmental friendliness is rapidly rising due to its potential applications in construction, furniture and decoration. However, finding an easy-to-operate and environmentally friendly dye for bamboo is a necessary task because of the difficulty in treating the dyeing waste liquid of acid dyes and the complexity of the production process of reactive dyes.Five formulations involving metal polyphenol complexes were employed to straightforwardly produce eco-friendly dyed bamboo and the impact of various formulations on the light aging resistance of the dyed veneers was examined. The results indicated that the light resistance of bamboo veneer dyed with the solution containing only FeSO4·7H2O and tannic acid reached level 4, surpassing the undyed bamboo veneer by three levels. The mechanism of enhanced lightfastness of dyed bamboo veneer was elucidated by XPS analysis. The polyphenol iron complex serves a dual purpose: it absorbs ultraviolet rays and scavenges free radicals within the system. Additionally, it reduced the oxidation of phenolics in the substrate, transforming them into dark-colored quinone structures. This process enhanced the light-aging resistance of the finishing materials. Therefore, this work provides a simple and environmentally friendly method for changing the color of bamboo and provides a new idea for the selection of dyes for bamboo dyeing in actual production.

High-Performance Engineered Composites Biofabrication Using Fungi.

Various natural polymers offer sustainable alternatives to petroleum-based adhesives, enabling the creation of high-performance engineered materials. However, additional chemical modifications and complicated manufacturing procedures remain unavoidable. Here, a sustainable high-performance engineered composite that benefits from bonding strategies with multiple energy dissipation mechanisms dominated by chemical adhesion and mechanical interlocking is demonstrated via the fungal smart creative platform. Chemical adhesion is predominantly facilitated by the extracellular polymeric substrates and glycosylated proteins present in the fungal outer cell walls. The dynamic feature of non-covalent interactions represented by hydrogen bonding endows the composite with extensive unique properties including healing, recyclability, and scalable manufacturing. Mechanical interlocking involves multiple mycelial networks (elastic modulus of 2.8 GPa) binding substrates, and the fungal inner wall skeleton composed of chitin and ß-glucan imparts product stability. The physicochemical properties of composite (modulus of elasticity of 1455.3 MPa, internal bond strength of 0.55 MPa, hardness of 82.8, and contact angle of 110.2°) are comparable or even superior to those of engineered lignocellulosic materials created using petroleum-based polymers or bioadhesives. High-performance composite biofabrication using fungi may inspire the creation of other sustainable engineered materials with the assistance of the extraordinary capabilities of living organisms.

Activated carbon from Camellia oleifera shells for adsorption of Y(iii): experimental and DFT studies.

Yttrium is an important rare earth element and is widely used in fields such as special glass preparation, metallurgy, and materials science. However, it is difficult to recover yttrium ion waste from dilute solutions with traditional processes, resulting in a significant waste of rare earth resources. The simple, effective, and easy-to-operate adsorption method is the most promising method for recovering yttrium, which is of great significance for sustainable development of the rare earth industry. In this study, activated carbon was prepared from Camellia oleifera fruit shells (COS) using phosphoric acid activation, and efficient recovery of Y(iii) from the Camellia oleifera fruit shell activated carbon was studied. Adsorption equilibrium data showed that this activated carbon had a Y(iii) adsorption capacity of 35.41 mg g-1, indicating significant potential for recovery of yttrium ions. The adsorption of Y(iii) by the activated carbon prepared from COS was consistent with the Langmuir model, and the adsorption data were consistent with the pseudo second-order kinetic model, indicating that the adsorption process was primarily chemical adsorption. After adsorption, the surface of the activated carbon contained large amounts of N, O, and Y, indicating that Y(iii) was stably adsorbed. The mechanisms for adsorption of Y(iii) on three types of activated carbon were studied through DFT calculations. The results showed that Y(iii) interacted with the carbon atoms on the surfaces to form new chemical bonds. The yttrium ion adsorption capacities for the three different activated carbons decreased in the order C I > C II > C.

[4D bioprinting technology and its application in cardiovascular tissue engineering].

3D bioprinting technology is a rapidly developing technique that employs bioinks containing biological materials and living cells to construct biomedical products. However, 3D-printed tissues are static, while human tissues are in real-time dynamic states that can change in morphology and performance. To improve the compatibility between in vitro and in vivo environments, an in vitro tissue engineering technique that simulates this dynamic process is required. The concept of 4D printing, which combines "3D printing + time" provides a new approach to achieving this complex technique. 4D printing involves applying one or more smart materials that respond to stimuli, enabling them to change their shape, performance, and function under the corresponding stimulus to meet various needs. This article focuses on the latest research progress and potential application areas of 4D printing technology in the cardiovascular system, providing a theoretical and practical reference for the development of this technology.

Full-Wood Utilization Strategy toward a Directional Luminescent Solar Concentrator.

Luminescent solar concentrators (LSCs) have proven to be highly effective in enhancing the conversion efficiency of photovoltaic (PV) cells. However, the traditional LSCs always suffer from self-absorption and escape the losses of luminescence. To these challenges, this study presents an ingenious all-wood-based LSC (W-LSC) with directional light-concentrating capabilities. By converting lignin into fluorescent carbon quantum dots (CQDs) and integrating them into transparent cellulose channels in delignified wood, we achieved efficient directional luminescence transmission in the W-LSC is achieved. The synthesized lignin-based CQDs (L-CQDs) exhibited a large Stokes shift (0.63 eV) and a bright yellow emission (540 nm). The prepared W-LSC possessed an external optical efficiency (ηopt) along the longitudinal (L) direction of 4.60% under a low irradiation intensity (40 mW·cm-2). Besides, contributed to the low thermal conductivity (0.300 W·m-1·K-1) of wood, the W-LSC maintained an ηopt of 4.03% at a temperature of 65 °C. Furthermore, the W-LSC demonstrated high tensile strength (424 MPa) and light transmission (85%). By leveraging the advantages of wood, this approach provides a different solution for enhancing solar energy utilization and advancing sustainable building.

Dual Modification of P3-Type Layered Cathodes to Achieve High Capacity and Long Cyclability for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have garnered extensive attentions in recent years as a low-cost alternative to lithium-ion batteries. However, achieving both high capacity and long cyclability in cathode materials remains a challenge for SIB commercialization. P3-type Na0.67Ni0.33Mn0.67O2 cathodes exhibit high capacity and prominent Na+ diffusion kinetics but suffer from serious capacity decay and structural deterioration due to stress accumulation and phase transformations upon cycling. In this work, a dual modification strategy with both morphology control and element doping is applied to modify the structure and optimize the properties of the P3-type Na0.67Ni0.33Mn0.67O2 cathode. The modified Na0.67Ni0.26Cu0.07Mn0.67O2 layered cathode with hollow porous microrod structure exhibits an excellent reversible capacity of 167.5 mAh g-1 at 150 mA g-1 and maintains a capacity above 95 mAh g-1 after 300 cycles at 750 mA g-1. For one thing, the specific morphology shortens the Na+ diffusion pathway and releases stress during cycling, leading to excellent rate performance and high cyclability. For another, Cu doping at the Ni site reduces the Na+ diffusion energy barrier and mitigates unfavorable phase transitions. This work demonstrates that the electrochemical performance of P3-type cathodes can be significantly improved by applying a dual modification strategy, resulting in reduced stress accumulation and optimized Na+ migration behavior for high-performance SIBs.

Fabrication of a dual-focus artificial compound eye with improved imaging based on modified microprinting and air-assisted deformation.

Natural compound eyes inspire the development of artificial optical devices that feature a large field of view and fast motion detection. However, the imaging of artificial compound eyes dramatically depends on many microlenses. The single focal length of the microlens array significantly limits the actual applications of artificial optical devices, like distinguishing objects at different distances. In this study, a curved artificial compound eye for a microlens array with different focal lengths was fabricated by inkjet printing and air-assisted deformation. By adjusting the space of the microlens array, secondary microlenses were created between intervals of the primary microlens. The diameter/height of the primary and secondary microlens arrays are 75/25 µm and 30/9 µm, respectively. The planar-distributed microlens array was transformed into a curved configuration using air-assisted deformation. Compared with adjusting the curved base to distinguish objects at different distances, the reported technique features simplicity and is easy to operate. The applied air pressure can be used to tune the field of view of the artificial compound eye. The microlens arrays with different focal lengths could distinguish the objects at different distances without additional components. When the external objects move a small distance, they can be detected by the microlens arrays due to their different focal lengths. It could effectively improve the motion perception of the optical system. Moreover, the focusing and imaging performances of the fabricated artificial compound eye were further tested. The compound eye combines the advantages of monocular eyes and compound eyes, holding great potential for developing advanced optical devices with a large field of view and automatic variable-focus imaging.

Molecular cloning and functional characterization of BcTSA in the biosynthesis of indole alkaloids in Baphicacanthus cusia.

Baphicacanthus cusia (Nees) Bremek (B. cusia) is an essential traditional Chinese herb that is commonly used to treat colds, fever, and influenza. Indole alkaloids, such as indigo and indirubin, are the primary active constituents of B. cusia. The indole-producing reaction is crucial for regulating the flow of indole alkaloids metabolites along the pathways and coordinating primary and secondary product biosynthesis in plants. The tryptophan synthase alpha-subunit (TSA) can catalyse a process that produces indole, which is free to enter secondary metabolite pathways; however, the underlying potential mechanism of regulating indigo alkaloids synthesis remains unknown. Here, a BcTSA was cloned from the transcriptome of B. cusia. The BcTSA has a significant degree of similarity with other plant TSAs according to bioinformatics and phylogenetic analyses. Quantitative real-time PCR (RT-qPCR) research showed that BcTSA was dramatically enhanced in response to treatment with methyl jasmonate (MeJA), salicylic acid (SA), and abscisic acid (ABA), and was predominantly expressed in the stems as opposed to the leaves and rhizomes. Subcellular localization revealed that BcTSA is localized in chloroplasts, which is compatible with the fact that the conversion of indole-3-glycerol phosphate (IGP) to indole occurs in chloroplasts. The complementation assay results showed that BcTSA was functional, demonstrating that it was capable of catalyzing the conversion of IGP to indole. BcTSA was shown to stimulate the manufacture of indigo alkaloids including isatin, indigo, and indirubin when the gene was overexpressed in the hairy roots of Isatis indigotica. In conclusion, our research provides novel perspectives that might be applied to manipulating the indole alkaloid composition of B. cusia.

Evaluation of left ventricular myocardial work in patients with hyperthyroidism with different heart rates with noninvasive pressure-strain loop based on two-dimensional speck tracking imaging.

Background: We investigated the application value of no-invasive myocardial work in evaluating left ventricular (LV) function in patients with hyperthyroidism. Methods: Sixty-five patients with an initial hyperthyroidism diagnosis were sorted into tachycardia (group TH1, n=31) and without tachycardia (group TH2, n=34) groups. Thirty healthy participants served as the control group (group CON). LV strain parameters and LV myocardial work parameters were evaluated at rest. Each parameter's value in identifying myocardial damage was analyzed using receiver operating characteristic curves. The correlation of myocardial work parameters with global longitudinal strain (GLS), longitudinal peak strain dispersion (normalized by heart rate, PSDN), and systolic blood pressure (SBP) was analyzed. Results: There was no difference in classic echocardiographic parameters between the groups. Compared with that in group CON, GLS decreased in groups TH1 and TH2 (TH1 17.99%±2.21% and TH2: 19.00%±2.85% vs. 20.27%±1.49%; both P<0.05); there was no significant difference between groups TH1 and TH2. PSDN increased in groups TH1 and TH2 (TH1 73.13±19.51 ms and TH2 55.06±17.03 vs. 44.13±8.65 ms; both P<0.05); it was higher in group TH1 than in group TH2 (P<0.05). Myocardial global work efficiency (GWE) decreased in groups TH1 and TH2 {TH1 95% [interquartile range (IQR), 94-95%] and TH2 96% (IQR, 95-97%) vs. 97% (IQR, 96-97%); both P<0.05}; it was lower in group TH1 than in group TH2 (P<0.05). Global constructive work (GCW) decreased in group TH1 (1,865.29±284.13 vs. 2,030.33±252.52 mmHg%; P<0.05), but was not different from that in group TH2; there was no difference between groups TH2 and CON. Global wasted work (GWW) increased in groups TH1 and TH2 [TH1 83.00 (IQR, 74.00-97.00) mmHg% and TH2 69.50 (IQR, 51.25-84.25) vs. 50.50 (IQR, 40.75-65.25) mmHg%; both P<0.05]; it was higher in group TH1 than in group TH2 (P<0.05). The area under the GWE curve was the largest (area under the curve =0.835), and the optimal cutoff point was 96.5%, with a sensitivity of 0.83 and a specificity of 0.70. GWE and GCW were positively correlated with GLS and negatively correlated with PSDN. GWW was negatively correlated with GLS and positively correlated with PSDN. In group CON, GCW and GWW were positively correlated with SBP; GWE was not correlated with SBP. In groups TH1 and TH2, GCW was positively correlated with SBP, but not with GWW or GWE. Conclusions: Hyperthyroidism can significantly decrease the GWE and increase GWW of the left ventricle. This change is more pronounced in patients with tachycardia. Myocardial work could be a novel method for the evaluation of LV myocardial function in patients with hyperthyroidism.

Early Changes of Serum Interleukin 14α Levels Predicts the Response to Anti-PD-1 Therapy in Cancer.

Background: Programmed cell death-1 (PD-1) blockade has been shown to confer clinical benefit in cancer patients. Here, we assessed the level of serum interleukin 14α (IL14α) in patients receiving anti-PD-1 treatment. Methods: This prospective study recruited 30 patients with advanced solid cancer who received pembrolizumab treatment in Northern Jiangsu People's Hospital between April 2016 and June 2018. The western blot analysis was used to assess the expression level of serum IL14α in patients at baseline and after 2 cycles of treatment. Interleukin 14α was performed using the unpaired 2-tailed Student test. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared by the log-rank test. Results: The early change of IL14α after 2 cycles of anti-PD-1 therapy was calculated as delta IL14α % change = (IL14α level after 2 cycles - IL14α level before treatment)/IL14α level before treatment × 100%. Receiver operating characteristic (ROC) was analyzed to get a cutoff point of delta IL14α % change as 2.46% (sensitivity = 85.71%, specificity = 62.5%; area under the ROC curve [AUC] = 0.7277, P = .034). Using this cutoff to subgroup the patients, an improved objective response rate was observed in patients with a delta IL14α change higher than 2.46% (P = .0072). A delta IL14α change over 2.46% was associated with a superior PFS (P = .0039). Conclusions: Early changes of serum IL14α levels may be a promising biomarker to predict outcomes in patients with solid cancer following anti-PD-1 treatment.