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Articular cartilage is a tissue with relatively poor self‐regeneration capacity due to insufficient blood vessels and chondrocytes in the region. Biomaterial‐assisted tissue engineering has shown great potential in cartilage regeneration. However, there are still many worries over the uses of exogenous growth factors, stem cells and scaffolds. To address these concerns, here a dynamic proteinaceous hydrogel with a self‐recruiting ability of cartilage‐inducing factor for in situ cartilage regeneration is reported. The dynamic hydrogel (Pep‐GelSH) is prepared by using thiol‐modified gelatin and thiol‐capped TGF‐β1‐affinity peptide through the Au‐S coordination. The injectability and self‐recovery of Pep‐GelSH hydrogel enabled not only minimally invasive implantation but also the adaptability of the scaffold to irregular defect shapes. Meanwhile, the dynamic hydrogel showed improved adherence to the host tissue and allowed quick infiltration of host cells. More importantly, the hydrogel significantly enhanced local enrichment of endogenous TGF‐β1 and led to the recruitment of stem cells in vivo. After implantation, the hydrogel scaffold triggered the innate repair capacity of cartilage defects by successively promoting stem cells recruitment, infiltration and differentiation, resulting in significantly enhanced chondrogenesis and improved cartilage repair. Therefore, the study in this work may provide a feasible and promising approach for in situ cartilage regeneration. [ABSTRACT FROM AUTHOR]

Piezoelectric cantilever beams are broadly implemented in energy harvesting. However, simple cantilever‐shaped harvesters are mostly unimodal. Herein, a T‐shaped cantilever beam harvester that can have a bimodal amplitude–frequency curve is developed. The modal of the system is designed in COMSOL finite‐element software and the dynamic behavior is carried out using the finite element simulation. Then, validation experiments are used to estimate the results of finite‐element analysis and it is concluded that the simulation results are in good agreement with the experimental data. Furthermore, the frequency response curves are plotted for various system parameters so as to discuss the influence of these parameters on the bandwidth of the harvester. It is found that there is an optimal resistance that can obtain the P = 2.87 mW maximum power. Finally, theoretical modeling is established and exact analytical solutions are derived, and the comparisons of theoretical, numerical, and experimental results are implemented. It is found that the results of these three methods are consistent. In addition, all of these predictions show that the bidirectional coupling induces the bandwidth increases. [ABSTRACT FROM AUTHOR]

Maintaining high conversion under the premise of high oxygenates selectivity in syngas conversion is important but a formidable challenge in Rh catalysis. Monometallic Rh catalysts provide poor oxygenate conversion efficiency, and efforts have been focused on constructing adjacent polymetallic sites; however, the one‐pass yields of C2+ oxygenates over the reported Rh‐based catalysts were mostly <20 %. In this study, we constructed a monometallic Rh catalyst encapsulated in UiO‐67 (Rh/UiO‐67) with enhanced proximity to dual‐site Rh1,2‐Rhn ensembles. Unexpectedly, this catalyst exhibited high efficacy for oxygenate synthesis from syngas, giving a high oxygenate selectivity of 72.0 % with a remarkable CO conversion of 50.4 %, and the one‐pass yield of C2+ oxygenates exceeded 25 %. The state‐of‐the‐art characterizations further revealed the spontaneous formation of an ensemble of Rh single atoms/dimers (Rh1,2) in the proximity of ultrasmall Rh clusters (Rhn) confined within the nanocavity of UiO‐67, providing adjacent Rh+‐Rh0 dual sites dynamically during the reaction that promote the relay of the undissociated CHO species to the CHx species. Thus, our results open a new route for designing highly efficient Rh catalysts for the conversion of syngas to oxygenates by precisely tuning the ensemble and proximity of the dual active sites in a confined space. [ABSTRACT FROM AUTHOR]

Maintaining high conversion under the premise of high oxygenates selectivity in syngas conversion is important but a formidable challenge in Rh catalysis. Monometallic Rh catalysts provide poor oxygenate conversion efficiency, and efforts have been focused on constructing adjacent polymetallic sites; however, the one‐pass yields of C2+ oxygenates over the reported Rh‐based catalysts were mostly <20 %. In this study, we constructed a monometallic Rh catalyst encapsulated in UiO‐67 (Rh/UiO‐67) with enhanced proximity to dual‐site Rh1,2‐Rhn ensembles. Unexpectedly, this catalyst exhibited high efficacy for oxygenate synthesis from syngas, giving a high oxygenate selectivity of 72.0 % with a remarkable CO conversion of 50.4 %, and the one‐pass yield of C2+ oxygenates exceeded 25 %. The state‐of‐the‐art characterizations further revealed the spontaneous formation of an ensemble of Rh single atoms/dimers (Rh1,2) in the proximity of ultrasmall Rh clusters (Rhn) confined within the nanocavity of UiO‐67, providing adjacent Rh+‐Rh0 dual sites dynamically during the reaction that promote the relay of the undissociated CHO species to the CHx species. Thus, our results open a new route for designing highly efficient Rh catalysts for the conversion of syngas to oxygenates by precisely tuning the ensemble and proximity of the dual active sites in a confined space. [ABSTRACT FROM AUTHOR]

Objective: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. Methods: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. Results: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. Conclusion: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy. [ABSTRACT FROM AUTHOR]

Background: Kaposiform hemangioendothelioma (KHE) is a rare neoplasm of vascular origin. It may involve skin, bone, connective tissue, and parenchymal organs, and it is difficult to make a definite diagnosis in the early stage because Kasabach-Merritt phenomenon may occur in some cases. Case presentation: On June 12, 2022, a 19-month boy was admitted to our department with the chief complaint of flexion of the right hip joint for over 1 year. An exploratory laparotomy and pelvic lesion resection were conducted and the resection of the iliopsoas muscle mass was performed. The intraoperative resection of the neoplasm confirmed the pathological diagnosis of kaposiform hemangioendothelioma. The vital signs of the child were stable and recovered well after surgery, and the platelet and coagulation indices were normal. Conclusion: KHE is a rare disease in clinics, the number of confirmed cases in the world is still relatively few, and the etiology and mechanism of the disease are still unknown, which could result in misdiagnose and delayed treatment in the disease early stages. It is necessary to continue to collect relevant cases, to unify the standard treatment guidelines as soon as possible, to reduce the mortality rate, and to improve the quality of life of the cases. [ABSTRACT FROM AUTHOR]

Background: Estrogen deficiency-mediated hyperactive osteoclast represents the leading role during the onset of postmenopausal osteoporosis. The activation of a series of signaling cascades triggered by RANKL-RANK interaction is crucial mechanism underlying osteoclastogenesis. Vorinostat (SAHA) is a broad-spectrum pan-histone deacetylase inhibitor (HDACi) and its effect on osteoporosis remains elusive. Methods: The effects of SAHA on osteoclast maturation and bone resorptive activity were evaluated using in vitro osteoclastogenesis assay. To investigate the effect of SAHA on the osteoclast gene networks during osteoclast differentiation, we performed high-throughput transcriptome sequencing. Molecular docking and the assessment of RANKL-induced signaling cascades were conducted to confirm the underlying regulatory mechanism of SAHA on the action of RANKL-activated osteoclasts. Finally, we took advantage of a mouse model of estrogen-deficient osteoporosis to explore the clinical potential of SAHA. Results: We showed here that SAHA suppressed RANKL-induced osteoclast differentiation concentration-dependently and disrupted osteoclastic bone resorption in vitro. Mechanistically, SAHA specifically bound to the predicted binding site of RANKL and blunt the interaction between RANKL and RANK. Then, by interfering with downstream NF-κB and MAPK signaling pathway activation, SAHA negatively regulated the activity of NFATc1, thus resulting in a significant reduction of osteoclast-specific gene transcripts and functional osteoclast-related protein expression. Moreover, we found a significant anti-osteoporotic role of SAHA in ovariectomized mice, which was probably realized through the inhibition of osteoclast formation and hyperactivation. Conclusion: These data reveal a high affinity between SAHA and RANKL, which results in blockade of RANKL-RANK interaction and thereby interferes with RANKL-induced signaling cascades and osteoclastic bone resorption, supporting a novel strategy for SAHA application as a promising therapeutic agent for osteoporosis. [ABSTRACT FROM AUTHOR]

In this work, we develop a complete robotic system to enable the robot to fulfill object-independent cooperative grasp tasks. The human subject initiates a task by either holding the object in hand or placing the object on the table. The human intention is inferred through body motions, after which the robot selects the corresponding grasp strategy. A novel real-time grasp detection model is proposed to choose the best picking locations according to the object’s shape. This module enables the robot to grasp any object placed on the table. Moreover, if handover grasp task is triggered, the hand pixels are detected and filtered out from candidate grasp poses for safety purpose. The proposed grasp detection model is evaluated on two public grasping datasets and a set of casual objects. The best model variant can achieve accuracy of 97.8% and 96.6% on image-wise splitting and object-wise splitting tests on Cornell Grasp Dataset respectively. The Jacquard Dataset accuracy is 93.9%. The overall system is also evaluated on real cooperative grasp tasks. The experimental results show effectiveness of the proposed robot grasp detection and implementation system. [ABSTRACT FROM AUTHOR]

C22H20O5, orthorhombic, P212121 (no. 19), a = 5.8585(3) Å, b = 16.2727(10) Å, c = 18.4886(11) Å, V = 1762.59(18) Å3, Z = 4, Rgt(F) = 0.0276, wRref(F2) = 0.0700, T = 100(2) K. [ABSTRACT FROM AUTHOR]

Bronchoscopic lung volume reduction (BLVR) is a feasible, safe, effective and minimally invasive technique to significantly improve the quality of life of advanced severe chronic obstructive pulmonary disease (COPD). In this study, three‐dimensional computed tomography (3D‐CT) automatic analysis software combined with pulmonary function test (PFT) was used to retrospectively evaluate the postoperative efficacy of BLVR patients. The purpose is to evaluate the improvement of lung function of local lung tissue after operation, maximize the benefits of patients, and facilitate BLVR in the treatment of patients with advanced COPD. All the reported cases of advanced COPD patients treated with BLVR with one‐way valve were collected and analysed from 2017 to 2020. Three‐dimensional‐CT image analysis software system was used to analyse the distribution of low‐density areas <950 Hounsfield units in both lungs pre‐ and post‐ BLVR. Meanwhile, all patients performed standard PFT pre‐ and post‐operation for retrospective analysis. We reported six patients that underwent unilateral BLVR with 1 to 3 valves according to the range of emphysema. All patients showed a median increase in forced expiratory volume in 1 second (FEV1) of 34%, compared with baseline values. Hyperinflation was reduced by 16.6% (range, 4.9%‐47.2%). The volumetric measurements showed a significant reduction in the treated lobe volume among these patients. Meanwhile, the targeted lobe volume changes were inversely correlated with change in FEV1/FEV1% in patients with heterogeneous emphysematous. We confirm that 3D‐CT analysis can quantify the changes of lung volume, ventilation and perfusion, to accurately evaluate the distribution and improvement of emphysema and rely less on the observer. [ABSTRACT FROM AUTHOR]

Objective: Investigate the use of endobronchial ultrasonography with a guide sheath (EBUS-GS) combined with Gene Xpert MTB/RIF (Xpert) for diagnosis of Mycobacterium tuberculosis (MTB) infection in isolated pulmonary nodules. Methods: Patients who had isolated pulmonary nodules and unknown diagnoses at our institution from October 2020 to December 2021 were prospectively examined using EBUS-GS and Xpert. The diagnostic values of using EBUS-GS or bronchoalveolar lavage fluid (BALF) with acid-fast staining, MGIT 960 culture, pathological examination, and Xpert for isolated pulmonary nodules caused by MTB infection were compared using receiver operating characteristic (ROC) analysis. Results: There were 135 patients, 64 with isolated pulmonary tuberculomas and 71 with non-tuberculous lesions. The sensitivity of EBUS-GS with Xpert was significantly higher than BALF with Xpert (57.81% vs. 34.78%, P = 0.017). Use of EBUS-GS with Xpert and MGIT 960 culture further increased the sensitivity to 62.50% (95%CI 50.64–74.36) and increased the specificity to 100%. The AUC values of BALF with MGIT 960 culture was 0.663(95%CI 0.543–0.783) and BALF with Xpert was 0.674 (95%CI 0.556–0.792). The AUC values of EBUS-GS with MGIT 960 culture was 0.680 (95%CI 0.554–0.743), with pathological examination was 0.713 (95%CI 0.573–0.760), and with Xpert was 0.789 (95%CI 0.655–0.829). Conclusion: Use of EBUS-GS with Xpert had high sensitivity and specificity in the diagnosis of isolated pulmonary tuberculoma. This method has significant potential for use in clinical practice. [ABSTRACT FROM AUTHOR]

Objective To investigate the endoscopic transoral - medial pterygomandibular fold approach anatomic procedures for jugular foramen, and to analyze the clinical feasibility of this approach. Methods and Results In the anatomical laboratory of the Surgical Treatment Technology Innovation Unit of Nasal Skull Base Tumor in Eye & ENT Hospital of Fudan University, a total of 5 specimens of necroheads (10 sides) were taken as research objects to simulate the anatomical steps of entering the jugular foramina and its adjacent structures through the oral pterygomandibular fold medial approach, and observe and describe important anatomical markers. 1) Anatomical procedures of the jugular foramen: firstly, the soft palate mucosa and suprapharyngeal retractive muscle were cut through the medial incision of pterygomandibular fold to enter anterior parapharyngeal space, the adipose tissue in the space was removed, and the stylopharyngeal fascia and stylopharyngeal muscle group were exposed. After the stylopharyngeal fascia was removed, the internal carotid artery (ICA) was further exposed and the jugular foramen was exposed. 2) The jugular foramen and its adjacent anatomical structures: the upper boundary of the jugular foramen was jugular bulbous fossa, the anterior was ICA, the anterolateral lateral was styloid process, the posterolateral boundary was the lateral rectus of head and transverse process of atlas, the medial boundary was the hypoglossal nerve and medial of occipital condyle, and the lateral boundary was the mastoid, digastric and facial nerves. Conclusions Endoscopic transoral-medial pterygomandibular fold approach for jugular foramen has better visual field, wider exposure range and shorter path. [ABSTRACT FROM AUTHOR]

Background: Many studies have shown that circular RNAs (circRNAs) are abnormally expressed in various tumor tissues and served as a key regulator in the occurrence and development of cancer. However, in hepatocellular carcinoma (HCC), the molecular mechanism of circRNAs in body fluids remains to be further explored. Methods: The expression levels of genes and proteins were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting, respectively. Cell counting Kit‐8 (CCK‐8), 5‐Ethynyl‐2'‐deoxyuridine (EdU), wound healing assay, Transwell assays, flow cytometry, and tumor formation models in nude mice were conducted to investigate the effects of circFAM114A2 on HCC cells both in vitro and in vivo. RNA antisense purification (RAP), dual luciferase reporter assays and rescue assays were carried out to verify the interaction between circFAM114A2, miR‐630 and HHIP. Results: CircFAM114A2 was significantly downregulated in HCC tissues and was associated with microvascular invasion and lymph node metastasis of HCC patients. We also observed that circFAM114A2 was lowly expressed in HCC plasma, which may serve as an effective biomarker to screen HCC patients from healthy controls (area under curve (AUC)=0.922). In vitro, circFAM114A2 overexpression significantly blunted HCC cell proliferation, migration, invasion, and promoted apoptosis, whereas circFAM114A2 silencing posed opposite effects. In vivo, circFAM114A2 overexpression inhibited the growth of HCC cells. Mechanistically, circFAM114A2 could increase the expression of the tumor suppressor HHIP via acting as a sponge for miR‐630. Conclusions: CircFAM114A2 exerts a tumor suppressor role in HCC through miR‐630/HHIP axis, and may be served as a potential diagnostic and therapeutic biomarker for HCC patients. [ABSTRACT FROM AUTHOR]

Programmed cell death protein 1 (PD-1), expressed on tumor-infiltrating T cells, is a T cell exhaustion marker. The mechanisms underlying PD-1 upregulation in CD4 T cells remain unknown. Here we develop nutrient-deprived media and a conditional knockout female mouse model to study the mechanism underlying PD-1 upregulation. Reduced methionine increases PD-1 expression on CD4 T cells. The genetic ablation of SLC43A2 in cancer cells restores methionine metabolism in CD4 T cells, increasing the intracellular levels of S-adenosylmethionine and yielding H3K79me2. Reduced H3K79me2 due to methionine deprivation downregulates AMPK, upregulates PD-1 expression and impairs antitumor immunity in CD4 T cells. Methionine supplementation restores H3K79 methylation and AMPK expression, lowering PD-1 levels. AMPK-deficient CD4 T cells exhibit increased endoplasmic reticulum stress and Xbp1s transcript levels. Our results demonstrate that AMPK is a methionine-dependent regulator of the epigenetic control of PD-1 expression in CD4 T cells, a metabolic checkpoint for CD4 T cell exhaustion. The deprivation of amino acids in the tumor microenvironment affects T cell survival and activation. Here the authors show that reduced levels of methionine are associated with PD1 upregulation in CD4+ T cells and that methionine supplementation promotes CD4+ T cell dependent anti-tumor immune responses. [ABSTRACT FROM AUTHOR]

C20H18ClNO3, monoclinic, P21 (no. 4), a = 6.3252(4) Å, b = 7.3424(5) Å, c = 17.8513(12) Å, β = 90.902(2)°, V = 828.95(10) Å3, Z = 2, Rgt(F) = 0.0223, wRref(F2) = 0.0593, T = 100(2) K. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the diagnostic performance of endobronchial ultrasound with Xpert MTB/RIF Ultra (Ultra) for detecting smear-negative pulmonary tuberculosis (TB). Methods: 143 patients suspected of sputum smear-negative pulmonary tuberculosis were enrolled in this study in Shanghai Pulmonary Hospital, China. These patients underwent endobronchial ultrasound with a guide sheath (EBUS-GS) or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) based on their chest CT manifestations. We assessed the sensitivity and specificity of tissue specimens with Ultra in the TB group and non-TB group. Culture and clinical diagnosis were used as gold-standard for TB. Results: Among these 143 patients, 11 patients were culture-positive TB, 85 patients were diagnosed with culture-negative TB and 47 were with the non-TB diseases. Direct testing with microscopy (Acid-Fast Bacilli smear, AFB), liquid culture, pathology, Xpert MTB/RIF(Xpert) test and Ultra had a sensitivity of 8.3%, 11.5%, 42.7%, 64.6%, and 78.1% individually among all the TB patients. Ultra had a higher sensitivity than Xpert (P = 0.011). But Ultra had a specificity of 59.6% (95% CI 44.3–73.3), lower than that of Xpert (89.4%, 95% CI 76.1–96.0, P = 0.001). Ultra had the same sensitivity on specimens from EBUS-TBNA and EBUS-GS (P = 0.975). Ultra's positive predictive value and negative predictive value were 79.8% and 57.1% respectively. Conclusions: Tissue specimens from interventional bronchoscopy combined with Ultra provide a sensitive method for diagnosing smear-negative pulmonary tuberculosis, but its specificity was lower than Xpert. [ABSTRACT FROM AUTHOR]

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Using lactic acid bacteria (LAB) to ferment Huyou peel and pomace could provide a reference for making full use of Huyou resources and provide valuable suggestions for the industrial production of functional foods. The effects of LAB fermentation on the bioactive composition, volatile compounds and antioxidant activity of Huyou peel and pomace were studied. Results showed that both Huyou peel and pomace were good substrates for LAB growth. LAB had remarkable influence on bioconversion of organic acids, among which ascorbic acid content was increased significantly. In addition, LAB could produce flavonoids with enhanced bioactivity and absorption. In particular, the contents of rhoifolin, quercitrin and quercetin were increased by over 100%. Besides, the volatile compounds contents and aroma complexity were improved. Furthermore, the antioxidant activity was enhanced. Thus, our study provides high-value applications of Huyou, and fermented products with improved nutritional value and flavor are potentially beneficial to human health. [ABSTRACT FROM AUTHOR]

Argostemma ehuangzhangense, a new Rubiaceae species from E'huangzhang Nature Reserve, Guangdong Province, China, is here described and illustrated. A morphological comparison between the new species and its putative relatives, A. lamxayanum, A. laotica and A. verticillatum, is presented. The new species is mostly similar to A. laotica, but they can be distinguished from each other since Argostemma ehuangzhangense presents solitary flower (vs. 2-flowered inflorescences), flower lobes 4 (vs. 5) and anthers opening by longitudinal slits (vs. apical pores). In a preliminary IUCN Red List status of Argostemma ehuangzhangense this species is assigned as Vulnerable (VU). [ABSTRACT FROM AUTHOR]

Increased bone resorption by osteoclasts after estrogen deficiency is the main cause of postmenopausal osteoporosis. TET2 (tet methylcytosine dioxygenase 2) is a DNA demethylase that regulates cellular function and differentiation potential. Macroautophagy/autophagy maintains cellular homeostasis by recycling unnecessary and damaged organelles. This study revealed that TET2 promoted bone loss in oophorectomized (OVX) mice and that TET2 promoted osteoclast differentiation by regulating autophagy. Tet2 knockdown inhibited autophagy and osteoclast differentiation in vitro. Mechanistically, Tet2 knockdown increased BCL2 (B cell leukemia/lymphoma 2) expression and BCL2 exhibited increased binding to BECN1 and negatively regulated autophagy. Small interfering RNA specific to Bcl2 interfered with BCL2 expression in Tet2-knockdown bone marrow cells/precursors, partially reversing autophagy dysregulation and promoting osteoclast differentiation. Moreover, the LV-shTet2 lentivirus prevented bone loss in OVX mice. In summary, our findings provide evidence that TET2 promotes osteoclast differentiation by inhibiting BCL2 expression and positively regulating BECN1-dependent autophagy. Abbreviations: ACP5/TRAP: acid phosphatase 5, tartrate resistant; ATP6V0D2: ATPase, H+ transporting, lysosomal V0 subunit D2; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, autophagy related; BMs: bone marrow cells; CTSK: cathepsin K; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MMP9: matrix metallopeptidase 9; OVX: oophorectomy; RUNX1: runt related transcription factor 1; SOCS3: suppressor of cytokine signaling 3; SPI1/PU.1: Spi-1 proto-oncogene; TNFSF11/RANKL: tumor necrosis factor (ligand) superfamily, member 11; TET2: tet methylcytosine dioxygenase 2. [ABSTRACT FROM AUTHOR]

Traditional anthropometric evaluation needs professional measuring tools and operations, and it is time-consuming, expensive, and not suitable for virtual try-on. As the mobile internet develops, the issue of human body reconstruction toward virtual try-on needs to be tackled. This paper proposes a rapid human body reconstruction method for virtual try-on based on multidimensional dense net (MDD-Net) on mobile terminal. MDD-Net takes fusion features as input and predicts 3D human body model. The acquisition of fusion features and the display of 3D human body are implemented on mobile toward virtual try-on. In the learning fuzzy anthropometric feature module, the example-guided fuzzy anthropometric feature matrix is acquired and default coding elements are interpolated. In the learning multi-perspective silhouette feature module, the fine human body shape features are learned based on DenseNet201. A related fusion feature data set is generated for the training and testing of MDD-Net. Compared to shape pose estimation models, the shape representation spaces of HMR and SMPLify are only 20.34% and 7.59% of our method, and their prediction accuracies are approximately 50% of our method. Compared to accurate shape estimation models, our method is more robust against the pose and perspective noise. The prediction accuracies of our method are improved by 13.34%, 55.77%, 34.6%, and 43.4%, 37.2% 9.0% on four test sets. Extensive experiments have demonstrated the superiority of our method for human body shape estimation toward virtual try-on. [ABSTRACT FROM AUTHOR]

Background: To observe the effect and mechanism of alpha-adrenergic receptor inhibitor phentolamine (PTL) in a rabbit model of acute pulmonary embolism (APE) combined with shock. Methods: Twenty-four New Zealand rabbits were randomly divided into sham operation group (S group, n = 8), model group (M group, n = 8) and PTL group (n = 8), the model of APE combined with shock was established. Mean pulmonary arterial pressure (MPAP), peripheral mean arterial pressure (MAP) and pulmonary circulation time were evaluated. The expression levels of α1 receptor, α2 receptor and their downstream molecules in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions lung tissues were detected and compared, respectively. Results: In M group, α receptor-related signaling pathways were significantly activated in both PE and non-PE areas as expressed by up-regulated α1, α2 receptor and phospholipase C (PLC); the expression level of phosphorylated protein kinase A (p-PKA) was significantly down-regulated; myosin light chain kinase (MLCK) and α-smooth muscle actin (α-SMA) levels were up-regulated. PTL treatment significantly improved pulmonary as well as systemic circulation failure: decreased MPAP, restored blood flow in non-PE area, shortened pulmonary circulation time, increased MAP, and restored the circulation failure. PTL induced significantly down-regulated expression of α1 receptor and its downstream molecule PLC in both PE and non-PE area, the expression level of α2 receptor was also down-regulated, the expression level of p-PKA was significantly up-regulated. PTL treatment can inhibit both α1 and α2 receptor-related signaling pathways in whole lung tissues, and inhibit Ca2+ signaling pathways. The expression level of MLCK and α-SMA were significantly down-regulated. Compared with PE area, the changes of expression levels of α receptor and its downstream molecules were more significant in the non-PE region. Conclusion: In this model of APE combined with shock, the sympathetic nerve activity was enhanced in the whole lung, α1 and α2 receptor and their downstream signaling activation might mediate blood flow failure in the whole lung. PTL treatment can effectively restore pulmonary blood flow in non-PE area and improve pulmonary as well as systemic circulation failure possibly through down-regulating α1 and α2 receptor and their downstream signaling pathways. [ABSTRACT FROM AUTHOR]

Data on safety and immunogenicity of coronavirus disease 2019 (COVID‐19) vaccinations in hepatocellular carcinoma (HCC) patients are limited. In this multicenter prospective study, HCC patients received two doses of inactivated whole‐virion COVID‐19 vaccines. The safety and neutralizing antibody were monitored. Totally, 74 patients were enrolled from 10 centers in China, and 37 (50.0%), 25 (33.8%), and 12 (16.2%) received the CoronaVac, BBIBP‐CorV, and WIBP‐CorV, respectively. The vaccines were well tolerated, where pain at the injection site (6.8% [5/74]) and anorexia (2.7% [2/74]) were the most frequent local and systemic adverse events. The median level of neutralizing antibody was 13.5 (interquartile range [IQR]: 6.9–23.2) AU/ml at 45 (IQR: 19–72) days after the second dose of vaccinations, and 60.8% (45/74) of patients had positive neutralizing antibody. Additionally, lower γ‐glutamyl transpeptidase level was related to positive neutralizing antibody (odds ratio = 1.022 [1.003–1.049], p = 0.049). In conclusion, this study found that inactivated COVID‐19 vaccinations are safe and the immunogenicity is acceptable or hyporesponsive in patients with HCC. Given that the potential benefits may outweigh the risks and the continuing emergences of novel severe acute respiratory syndrome coronavirus 2 variants, we suggest HCC patients to be vaccinated against COVID‐19. Future validation studies are warranted. [ABSTRACT FROM AUTHOR]

Quantification and classification of tissue features such as glomerulus are important elements of the histopathologic assessment of renal tissue. To fulfill this task, glomerulus segmentation is required. In this paper, we propose a multi-stream glomerulus segmentation framework based on three signature models: FCN, Deeplabv3 and Unet. Resnet is combined with FCN and Deeplabv3 model to enhance the encoding process. Meanwhile, Unet is upgraded to use EfficientNet as the backbone for feature extraction. Each individual model will output a local decision. On top of these base learners, ensemble approaches are proposed for robust performance through prediction aggregation. Among all the ensemble methods, the Bayesian voting method performs best and achieves F-score of 91.5% [ABSTRACT FROM AUTHOR]

Purpose: The disinfection robot developed by the authors and team focuses on achieving fast and precise disinfection under a given or specific disinfection zone. This looks to solve problems with traditional robots that pay less attention to the level, efficiency and zones of disinfection. To effectively support and guarantee normal running for the whole system, a digital twin system is applied to the disinfection robot. This study aims to achieve fast, precise and thorough disinfection via the developed mobile robot. Design/methodology/approach: The designed robot is composed primarily of the following three parts: a mobile platform, a six-axis robotic arm and a ultraviolet-C (UVC) LED array. The UVC LED array is installed on the end-effector to achieve large-scale, precise manipulation. The adoption of all types of advanced sensors and the development of an intuitive and user-friendly client interface are helpful in achieving remote control, path planning, data monitoring and custom disinfection functions. Findings: Disinfection of three different locations in the laboratory was performed; the dosage distribution of the surface as radiated by the UVC robot was detected; and feasibility of development was validated. Originality/value: The developed disinfection robot achieved fast, precise and thorough disinfection for a given or specific disinfection zone. [ABSTRACT FROM AUTHOR]

This paper presents a complete robotic portrait drawing system. First, facial features are extracted robustly using deep learning-based approaches. Then an efficient path planning algorithm is proposed to draw the portrait. To extract facial features, it goes through the following steps: face detection, facial edge extraction, image synthesis and image binarization. Given the processed image, the robot maps the coordinates of the image pixels to the coordinates of the drawing board after calibration. Then drawing paths are planned. The path planning principle is that the robot tries to travel as minimum distance as possible. To evaluate the proposed system, the facial landmarks are extracted from both the reference image and the binary image output of our system. Point-to-point distances are calculated to measure the binary image quality. On the other hand, the drawing time of each individual portrait is saved for efficiency comparison. [ABSTRACT FROM AUTHOR]

Objective: Preliminary clinical studies have confirmed that Shexiang Tongxin dropping pills (STDPs) could improve angina pectoris and attenuate vascular endothelial dysfunction in patients with slow coronary flow, but the underlying mechanism is not fully unclear. We aimed to investigate the impact of STDP in a swine model of coronary slow flow (SF) and related mechanisms. Methods: SF was induced by coronary injection of 40 μ m microspheres, and pigs were randomly divided into the SF group and SF plus STDP group. Pigs in the STDP group received sublingual STDP for 10 min, followed by 1 g STDP oral administration daily for 6 days. Coronary angiography was performed, the TIMI frame count (TFC) was determined, and hemodynamic measurements were performed before, at 30 min, and 7 days post-SF. Serum levels of total NO, NOS, ET-1, C-TNI, and BNP were measured. Myocardial expressions of TNF and IL-6, eNOS, VEGF, CD31, and α-SMA were analyzed by immunohistochemistry and Western blotting. Results: Compared to the SF group, LVEF and TFC were significantly improved at 7 days post-SF in the STDP group. The serum ET-1 level was significantly reduced at 7 days, and NO and NOS levels were significantly higher in the STDP group. Seven days post-SF, myocardial TNF and IL-6 expressions were significantly downregulated, while the expressions of eNOS and VEGF, CD31, and ɑ-SMA were significantly upregulated in the STDP group. Conclusion: Our results showed that STDP improved cardiac function and coronary flow, possibly through reducing inflammatory responses and upregulating myocardial eNOS and VEGF, CD31, and the ɑ-SMA expression. [ABSTRACT FROM AUTHOR]

Background: Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with compensated (C-cirrhosis) and decompensated cirrhosis (D-cirrhosis) are limited. Methods: In this prospective multicenter study, adult participants with C-cirrhosis and D-cirrhosis were enrolled and received two doses of inactivated whole-virion COVID-19 vaccines. Adverse events were recorded within 14 days after any dose of vaccination, and serum samples of enrolled patients were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Risk factors for negative neutralizing antibody were analyzed. Results: In total, 553 patients were enrolled from 15 centers in China, including 388 and 165 patients with C-cirrhosis and D-cirrhosis. The vaccines were well tolerated, most adverse reactions were mild and transient, and injection site pain (23/388 [5.9%] vs 9/165 [5.5%]) and fatigue (5/388 [1.3%] vs 3/165 [1.8%]) were the most frequently local and systemic adverse events in both the C-cirrhosis and D-cirrhosis groups. Overall, 4.4% (16/363) and 0.3% (1/363) of patients were reported Grades 2 and 3 alanine aminotransferase (ALT) elevations (defined as ALT > 2 upper limit of normal [ULN] but ≤ 5 ULN, and ALT > 5 ULN, respectively). The positive rates of COVID-19 neutralizing antibodies were 71.6% (278/388) and 66.1% (109/165) in C-cirrhosis and D-cirrhosis groups. Notably, Child–Pugh score of B and C levels was an independent risk factor of negative neutralizing antibody. Conclusions: Inactivated COVID-19 vaccinations are safe with acceptable immunogenicity in cirrhotic patients, and Child–Pugh score of B and C levels is associated with hyporesponsive to COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Periprosthetic osteolysis (PPO) triggered by wear particles is the most severe complication of total joint replacement (TJR) surgeries, representing the major cause of implant failure, which is public health concern worldwide. Previous studies have confirmed the specialized role of osteoclast-induced progressive bone destruction in the progression of PPO. Additionally, the reactive oxygen species (ROS) induced by wear particles can promote excessive osteoclastogenesis and bone resorption. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), a cellular enzyme, is considered to be responsible for the production of ROS and the formation of mature osteoclasts. However, NOX4 involvement in PPO has not yet been elucidated. Therefore, we investigated the mechanism by which NOX4 regulates osteoclast differentiation and the therapeutic effects on titanium nanoparticle-induced bone destruction. We found that NOX4 blockade suppressed osteoclastogenesis and enhanced the scavenging of intracellular ROS. Our rescue experiment revealed that nuclear factor-erythroid 2-related factor 2 (Nrf2) silencing reversed the effects of NOX4 blockade on ROS production and osteoclast differentiation. In addition, we found increased expression levels of NOX4 in PPO tissues, while NOX4 inhibition in vivo exerted protective effects on titanium nanoparticle-induced osteolysis through antiosteoclastic and antioxidant effects. Collectively, these findings suggested that NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway and that NOX4 blockade may be an attractive therapeutic approach for preventing PPO. [ABSTRACT FROM AUTHOR]

Uro-A, which is a metabolite of intestinal flora and mainly produced from pomegranates and some nuts, suppresses osteoclast formation and bone resorption by activating autophagy. Uro-A upregulated the expression of Beclin 1 and LC3 and modulated bone homeostasis 4 in BMMs, thus resulting in decreased osteoclast-related markers and bone loss. Senile osteoporosis (SOP) is a systemic bone disease that is significantly associated with age and eventually leads to deteriorated bone strength and increased fracture risk. Urolithin A (Uro-A) is a gut microbiome-derived compound that is mainly produced from pomegranates and some nuts. Uro-A has attracted great attention in recent years in view of its protective effects on aging-related diseases, including muscle dysfunction, kidney disease and knee injury. However, its protective influence and possible mechanisms in senile osteoporosis remain unclear. Our study describes the beneficial effect of Uro-A on bone marrow macrophages (BMMs). The in vitro results demonstrated that Uro-A inhibited receptor activator for nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in BMMs in a concentration-dependent manner. Uro-A significantly reduced the expression of osteoclast-related genes and bone resorption. Mechanistically, we found that the autophagy ability of BMMs was significantly enhanced in the early stage of Uro-A treatment, accompanied by the activation of LC3 and Beclin 1. At the same time, this enhanced autophagy activity was maintained until the later stage after stimulation with RANKL. Furthermore, we found that the MARK signaling pathway was blocked by Uro-A treatment. In a mouse model of aging, Uro-A effectively inhibited bone loss in the proximal femur, spine and tibia of aging mice. These results indicated that Uro-A is a robust and effective treatment for preventing senile osteoporosis bone loss. [ABSTRACT FROM AUTHOR]

Wear particle-induced periprosthetic osteolysis (PPO) have become a major reason of joint arthroplasty failure and secondary surgery following joint arthroplasty and thus pose a severe threat to global public health. Therefore, determining how to effectively suppress particle-induced PPO has become an urgent problem. The pathological mechanism involved in the PPO signaling cascade is still unclear. Recently, the interaction between osteogenic inhibition and wear particles at the implant biological interface, which has received increasing attention, has been revealed as an important factor in pathological process. Additionally, Hedgehog (Hh)-Gli1 is a crucial signaling cascade which was regulated by multiple factors in numerous physiological and pathological process. It was revealed to exert a crucial part during embryonic bone development and metabolism. However, whether Hh-Gli1 is involved in wear particle-induced osteogenic inhibition in PPO remains unknown. Our present study explored the mechanism by which the Hh-Gli1 signaling cascade regulates titanium (Ti) nanoparticle-induced osteolysis. We found that Hh-Gli1 signaling was dramatically downregulated upon Ti particle treatment. Mechanistically, glycogen synthesis kinase 3β (GSK-3β) activation was significantly increased in Ti particle-induced osteogenic inhibition via changes in GSK-3β phosphorylation level and was found to participate in the posttranslational modification and degradation of the key transcription factor Gli1, thus decreasing the accumulation of Gli1 and its translocation from the cytoplasm to the nucleus. Collectively, these findings suggest that the Hh-Gli1 signaling cascade utilizes a GSK3β-mediated mechanism and may serve as a rational new therapeutic target against nanoparticle-induced PPO. [ABSTRACT FROM AUTHOR]

Understanding disease-associated stem cell abnormality has major clinical implications for prevention and treatment of human disorders, as well as for regenerative medicine. Here we report a multifaceted study on airway epithelial stem cells in Tracheobronchopathia Osteochondroplastica (TO), an under-detected tracheobronchial disorder of unknown etiology and lack of specific treatment. Epithelial squamous metaplasia and heterotopic bone formation with abnormal cartilage proliferation and calcium deposits are key pathological hallmarks of this disorder, but it is unknown whether they are coincident or share certain pathogenic mechanisms in common. By functional evaluation and genome-wide profiling at both transcriptional and epigenetic levels, we reveal a role of airway basal cells in TO progression by acting as a repository of inflammatory and TGFβ-BMP signals, which contributes to both epithelial metaplasia and mesenchymal osteo-chondrogenesis via extracellular signaling and matrix remodeling. Restoration of microenvironment by cell correction or local pathway intervention may provide therapeutic benefits. Tracheobronchopathia osteoplastica (TO), is an underreported affliction characterized by squamous metaplasia and heterotopic bone formation in trachea and bronchi. Here the authors apply functional, as well as genome-wide transcriptional and epigenetic profiling to identify airway basal cells dysfunction underlying TO. [ABSTRACT FROM AUTHOR]

The association between fragmented QRS (fQRS) and autonomic nervous dysfunction, and major adverse cardiovascular events (MACE) is not fully clear in patients with acute myocardial infarction (AMI). This study aimed to observe whether combined assessment with fQRS and cardiac autonomic nervous function could enhance the predicting efficacy on outcome in AMI patients. A total of 153 consecutive hospitalized AMI patients were included in this retrospective study. Patients were divided into non-fQRS (nfQRS) group and fQRS group according to 12-lead electrocardiogram, into sHRV [severely depressed heart rate variability (HRV): standard deviation of NN intervals (SDNN) < 100 ms and very low frequency (VLF) < 26.7 ms] group and nsHRV (non-severely depressed HRV) group according to 24 h Holter monitoring, and into non-MACE (nMACE) group and MACE group according to 12 months' follow-up results. The incidence of sHRV was significantly higher in the fQRS group than in the nfQRS group (71.9 vs. 39.3%, p < 0.05). The incidences of MACE were 7.4, 22.2, 25.7 and 56.5%, respectively, in nsHRV + nfQRS group, nsHRV + fQRS group, sHRV + nfQRS group and sHRV + fQRS group (p < 0.05). Multivariable Cox regression analysis showed that patients in the sHRV + fQRS group had a sixfold higher risk of MACE compared to patients in the nsHRV + nfQRS group (HR = 6.228, 95% CI 1.849–20.984, p = 0.003). The predicting sensitivity and specificity on MACE were 81.4 and 58.2% by sHRV, 69.8 and 69.1% by fQRS in these AMI patients. The specificity (81.8%) was the highest with the combination of sHRV and fQRS. Adding sHRV and fQRS to clinical data offered incremental prognostic value. Present results indicate that fQRS is closely related to sHRV, suggesting significant impairment of sympathetic nerve function in AMI patients with fQRS. Combined assessment with fQRS and sHRV enhances the predicting efficacy on outcome in AMI patients. [ABSTRACT FROM AUTHOR]

Background: AMP-activated protein kinase (AMPK) is a metabolic sensor that maintains energy homeostasis. AMPK functions as a tumor suppressor in different cancers; however, its role in regulating antitumor immunity, particularly the function of regulatory T cells (Tregs), is poorly defined. Methods: AMPKα1fl/flFoxp3YFP-Cre, Foxp3YFP-Cre, Rag1−/−, and C57BL/6 J mice were used for our research. Flow cytometry and cell sorting, western blotting, immuno-precipitation, immuno-fluorescence, glycolysis assay, and qRT-PCR were used to investigate the role of AMPK in suppressing programmed cell death 1 (PD-1) expression and for mechanistic investigation. Results: The deletion of the AMPKα1 subunit in Tregs accelerates tumor growth by increasing the expression of PD-1. Metabolically, loss of AMPK in Tregs promotes glycolysis and the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme of the mevalonate pathway. Mechanistically, AMPK activates the p38 mitogen-activated protein kinase (MAPK) that phosphorylates glycogen synthase kinase-3β (GSK-3β), inhibiting the expression of PD-1 in Tregs. Conclusion: Our study identified an AMPK regulatory mechanism of PD-1 expression via the HMGCR/p38 MAPK/GSK3β signaling pathway. We propose that the AMPK activator can display synergic antitumor effect in murine tumor models, supporting their potential clinical use when combined with anti-PD-1 antibody, anti-CTLA-4 antibody, or a HMGCR inhibitor. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is a significant global health problem and > 42–52% of patients are infected during perinatal period. Tenofovir alafenamide fumarate (TAF) and tenofovir disoproxil fumarate (TDF) have been widely recognized as the main compounds used for antiviral treatment of hepatitis B. The present study evaluated the efficacy and safety of TAF in reducing HBV vertical transmission. Methods: A total of 72 pregnant women, who met the inclusion criteria, were randomly divided into the TDF (300 mg/day, n = 36) and TAF (25 mg/day, n = 36) groups. Clinical and laboratory data were analyzed and compared between the two groups. Results: No significant differences in alanine aminotransferase, total bilirubin, blood creatinine and blood urea nitrogen levels were noted between the two groups after treatment. The serum HBV DNA viral load and hepatitis B e antigen (HBeAg) levels of the two groups were significantly decreased following treatment, whereas the difference between the two groups was not statistically significant. The levels of urine retinol-binding protein and β2-microglobulin had no significant change after TAF treatment (p > 0.05), but increased significantly after TDF treatment (p < 0.05). All drug concentrations were undetectable in umbilical cord blood (UCB) and breast milk samples of the TAF group, while the drug concentration of UCB and breast milk samples in the TDF group was 2.98 ± 1.44 and 19.16 ± 15.26 ng/ml, respectively. All infants were tested negative for serum hepatitis B surface antigen, HBV DNA, and HBeAg. Conclusions: Both TAF and TDF effectively block the mother-to-child transmission of hepatitis B. TAF was superior to TDF with regard to renal safety and breastfeeding. [ABSTRACT FROM AUTHOR]

The gut-uterus axis plays a pivotal role in the pathogenesis of endometrial cancer (EC). However, the correlations between the endometrial microbiome and endometrial tumor transcriptome in patients with EC and the impact of the endometrial microbiota on hematological indicators have not been thoroughly clarified. In this prospective study, endometrial tissue samples collected from EC patients (n = 30) and healthy volunteers (n = 10) were subjected to 16S rRNA sequencing of the microbiome. The 30 paired tumor and adjacent nontumor endometrial tissues from the EC group were subjected to RNAseq. We found that Pelomonas and Prevotella were enriched in the EC group with a high tumor burden. By integrating the microbiome and hematological indicators, a correlation was observed between Prevotella and elevated serum D-dimer (DD) and fibrin degradation products (FDPs). Further transcriptome analysis identified 8 robust associations between Prevotella and fibrin degradation-related genes expressed within ECs. Finally, the microbial marker of Prevotella along with DD and FDPs showed a high potential to predict the onset of EC (AUC = 0.86). Our results suggest that the increasing abundance of Prevotella in endometrial tissue combined with high serum DD and FDP contents may be important factors associated with tumor burden. The microbe-associated transcripts of host tumors can partly explain how Prevotella promotes DD and FDPs. [ABSTRACT FROM AUTHOR]

Purpose: Microsatellite instability (MSI) and mismatch repair deficiency (dMMR) are important biomarkers for predicting responses to immune checkpoint inhibitor (ICI) therapies. Although PCR-based tests for high MSI (MSI-H) and dMMR yield highly concordant results in endometrial cancer (EC), it is unclear whether this is true for MSI-H and MMR detected by next-generation sequencing (NGS) and immunohistochemistry (IHC), respectively. This study investigated whether EC with MSI-H identified by NGS and dMMR identified by IHC have similar tumor immune microenvironments. Patients and Methods: EC tissue and corresponding peripheral blood lymphocyte samples were collected from 99 randomly selected patients. MSI status and tumor mutation burden (TMB) were examined by NGS. MMR protein and programmed death ligand (PD-L)1 expression and tumor-infiltrating lymphocyte (TIL) abundance were evaluated by IHC. Results: Of the 99 EC samples, 29 (29%) had dMMR by IHC, while 18 (18%) had MSI-H by NGS. MSI and MMR status identified by the two methods were discordant in the 99 EC patients, and 2/18 NGS-identified MSI-H patients (11%) retained MMR protein expression. MSI-H and dMMR endometrial tumors had similar numbers of cluster of differentiation (CD)3+ TILs (T cells) and CD8+ TILs (cytotoxic T cells) in the tumor center and periphery, which differed from those in microsatellite stable (MSS) and mismatch repair-proficient (pMMR) EC; they also showed similar TMB, PD-L1 expression, and TIL counts with higher TMB and PD-L1 expression than MSS and pMMR ECs. The abundance of CD3+ and CD8+ TILs was increased in PD-L1-positive EC. Conclusion: NGS-identified MSI status and IHC-identified MMR status were inconsistent in EC, and 11% of NGS-identified MSI-H tumors retained MMR protein expression. Conversely, MSI and MMR status determined by the two methods provided similar data on TMB, PD-L1 expression, and TIL abundance, which can guide treatment decisions with ICIs. [ABSTRACT FROM AUTHOR]

Blocking the mevalonate pathway for cholesterol reduction by using statin may have adverse effects including statin‐induced colitis. Moreover, one of the predisposing factors for colitis is an imbalanced CD4+ T cell, which can be observed on the complete deletion of HMG‐CoA reductase (HMGCR), a target of statins. In this study, we inquired geranylgeranyl pyrophosphate (GGPP) is responsible for maintaining the T‐cell homeostasis. Following dextran sulfate sodium (DSS)‐induced colitis, simvastatin increased the severity of disease, while cotreatment with GGPP, but not with cholesterol, reversed the disease magnitude. GGPP ameliorated DSS‐induced colitis by increasing Treg cells. GGPP amplified Treg differentiation through increased IL‐2/STAT 5 signaling. GGPP prenylated Ras protein, a prerequisite for extracellular signal‐regulated kinase (ERK) pathway activation, leading to increased IL‐2 production. Higher simvastatin dose increased the severity of colitis. GGPP ameliorated simvastatin‐increased colitis by increasing Treg cells. Treg cells, which have the capacity to suppress inflammatory T cells and were generated through IL‐2/STAT5 signaling, increased IL‐2 production through prenylation and activation of the Ras/ERK pathway. [ABSTRACT FROM AUTHOR]

The conversion from functional requirements (FRs) to design parameters is the foundation of product customization. However, original customer needs usually result in incomplete FRs, limited by customers' incomprehension on the design requirements of these products. As the incomplete FRs may undermine the design activities afterwards, managers need to develop an effective approach to predict the missing values of the FR. This study proposes an integrative approach to obtain the complete FR. The k nearest neighbor (KNN) algorithm is employed to predict the missing continuous variables in FR, using the improved distance formula for two incomplete FRs. Support vector machine (SVM) classifiers are adopted to classify the missing categorical variables in FR, combined with directed acyclic graph for multi-class classification. KNN and SVM are then integrated into a multi-layer framework to predict the missing values of FR, where categorical and continuous variables both exist. A case study on the elevator customization is conducted to verify that KNN-SVM is feasible in accurate prediction of elevator FR values. Furthermore, KNN-SVM outperforms other five single and five composite methods, with average reduction in root mean squared error (RMSE) of 39% and 21% against KNN and KNN-Tree, respectively. [ABSTRACT FROM AUTHOR]