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We investigate whether and how political diversity within corporate boards of directors and top management teams affect a firm’s environmental innovation performance. We employ personal political contributions’ data to measure political ideology distance among directors, and that within top management teams (TMTs). We predict that 1) political diversity (either board or TMTs) is positively associated with corporate environmental innovation; 2) firms’ environmental-related information disclosure mediates the effect of political diversity on environmental innovation; and 3) contextual factors (e.g., environmental partnership, product market competition, and state political diversity) moderate the effect of political diversity on environmental innovation. Taken together, we predict that our results lead us to conclude that political diversity in corporate boardrooms and TMTs is imperative for leadership effectiveness and corporate environmental innovation.

Background: To investigate and analyze the learning curve of totally thoracoscopic mitral valve replacement and provide a quantitative reference for cardiac surgeons to carry out the operation step by step. Methods: The clinical data were retrospectively analyzed of 100 consecutive patients with totally thoracoscopic mitral valve replacement successively performed by the same surgeon in a single center from May 2019 to June 2020. The learning curve was divided into 2 stages by using cumulative sum analysis, and relevant surgical parameters and perioperative indicators were analyzed. Results: The first stage of the learning curve is the skill acquisition stage, which includes 1 to 40 surgical procedures. The second stage is the proficiency stage, involving 41 to 100 operations. Among the surgical parameters of the patients in the 2 stages, detectable improvements were observed in operative time, cardiopulmonary bypass time, cross-clamp time, and intraoperative injury. After surgery, the amount of drainage, length of hospital stay, blood creatinine levels, and oxygenation index 24 h after surgery were also significantly different between the 2 groups (all P < .05). The age and sex distributions of the patients were balanced, and there was no statistically significant difference in terms of conversion to median sternotomy between the 2 stages (P > .05). Conclusions: Cumulative sum analysis was used to accurately analyze the learning curve of totally thoracoscopic mitral valve replacement, indicating that 40 cases are needed to master the technique.

Peritoneal loose body (PLB) is a rare clinical entity. It is generally agreed that the most common origin of the loose bodies is appendix epiploica. We here report a case of PLB that looks like a “boiled egg,” which was misdiagnosed preoperatively as a lesion of hepatic origin and was confirmed by operation and postoperative pathology. PLBs are rare entities, a good understanding of their specific imaging features can help prevent misdiagnosis, but sometimes an accurate preoperative diagnosis is still difficult to achieve. Exploratory laparoscopy is a recommended method for management of PLBs.

Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

Background The patch neointima technique is a modified valve-sparing aortic root repair surgery for acute type A aortic dissection and the short-term outcomes are satisfactory. The midterm outcomes have not been reported. Methods From January 2009 to December 2012, 147 patients underwent valve-sparing aortic root repair with the patch neointima technique for type A aortic dissection in our center. The midterm outcomes of the patients were evaluated by echocardiography and aortic computed tomography angiography. Results Of 147 patients, 32 patients (21.8%) underwent proximal arch repair, and 115 patients (78.2%) underwent proximal arch repair combined with triple-branched stent graft implantation. The perioperative mortality was 5.4%. Preoperative aortic insufficiency (AI) was observed in 94 patients (63.9%); 131 patients (89.1%) left the operating room with 0 AI; the remaining 16 patients (10.9%) had trace or less than 1+ AI. A total of 128 patients (87.1%) completed 7-year follow-up. The mean follow-up time was 5.7 ± 1.2 years. As many as 82% of patients (105) were 0 AI and 15.6% of patients (20) were 0.5+ trace or less than 1+ AI. No reoperation was performed for the aortic root. The diameters of sinotubular junction and sinus were reduced to the normal range (28.3 ± 4.2 mm and 30.5 ± 3.6 mm, respectively) and remained stable (28.9 ± 5.6 mm, P = .300, and 30.8 ± 4.2 mm, P = .540, respectively) during 7 years of follow-up. Conclusions Valve-sparing aortic root repair with patch neointima technique was associated with stable function of the aortic valves and no expansion of the aortic root in the midterm.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease, and its etiology and risk factors remain uncertain. AIM: To investigate the possible influence of Chinese herbal liquid containing geniposide on IMP. METHODS: The detailed formula of herbal liquid prescriptions of all patients was studied, and the herbal ingredients were compared to identify the toxic agent as a possible etiological factor. Abdominal computed tomography (CT) and colonoscopy images were reviewed to determine the extent and severity of mesenteric phlebosclerosis and the presence of findings regarding colitis. The disease CT score was determined by the distribution of mesenteric vein calcification and colon wall thickening on CT images. The drinking index of medicinal liquor was calculated from the daily quantity and drinking years of Chinese medicinal liquor. Subsequently, Spearman's correlation analysis was conducted to evaluate the correlation between the drinking index and the CT disease score. RESULTS: The mean age of the 8 enrolled patients was 75.7 years and male predominance was found (all 8 patients were men). The patients had histories of 5-40 years of oral Chinese herbal liquids containing geniposide and exhibited typical imaging characteristics (e.g., threadlike calcifications along the colonic and mesenteric vessels or associated with a thickened colonic wall in CT images). Calcifications were confined to the right-side mesenteric vein in 6 of the 8 patients (75%) and involved the left-side mesenteric vein of 2 cases (25%) and the calcifications extended to the mesorectum in 1 of them. The thickening of colon wall mainly occurred in the right colon and the transverse colon. The median disease CT score was 4.88 (n = 7) and the median drinking index was 5680 (n = 7). After Spearman's correlation analysis, the median CT score of the disease showed a significant positive correlation with the median drinking index (r = 0.842, P < 0.05). CONCLUSION: Long-term oral intake of Chinese herbal liquid containing geniposide may play a role in the pathogenesis of IMP.

Background: Cerebral infarction (CI) is a common disease with high morbidity and disability. Shuxuetong (SXT) injection is a Chinese Materia Medica standardized product used in the treatment of CI. Currently, there is a lack of high-quality evidence to support the effectiveness and safety of SXT on patients with CI. This systematic review protocol aims at describing a meta-analysis to evaluate the efficacy of SXT for the treatment of CI. Methods: We will search the databases of PubMed, MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, China national knowledge infrastructure database (CNKI), Wan fang database, Chongqing VIP information, and SinoMed from their inception to Jun 2020. Two reviewers will independently screen Randomized controlled trials of SXT for the treatment of CI. The meta-analysis will be conducted using RevMan V.5.3 software. Results: The results of this study will be published in a peer-reviewed journal. Conclusion: The conclusion of our systematic review will provide evidence to judge whether SXT is an effective intervention for patients with CI. Trial registration number: 10.17605/OSF.IO/3F6ZH.

Connected and autonomous vehicles is a disruptive technology that has the potential to transform the current transportation system by reducing traffic accidents and enhancing driving safety. One major challenge of building such a system is how to realize effective and efficient cooperative perception among vehicles, which enables them to share local (raw or processed) perception data with each other or roadside infrastructures through wireless communications. As machine learning techniques become prevalent in autonomous vehicles, particularly in their perception subsystem, we articulate the possibility to design a machine-learning-enabled cooperative perception system for connected autonomous vehicles. Not only are the research challenges in designing cooperative perception presented, but we also focus on how to reduce communication and data processing latency in order to meet the stringent time requirements posed by autonomous driving applications. The article outlines the research challenges and opportunities in designing cooperative perception for autonomous vehicles, leveraging the recent research outcomes from machine learning, feature map quantification, millimeter-wave communications, and vehicular edge computing.

Background The interference screw is the most popular device that fixes the graft for anterior cruciate ligament reconstruction, reducing the incidence of windshield effect and bungee effect. For the screw, either metallic, “bioresorbable,” or polyetheretherketone (PEEK) material is available. PEEK is popular and extensively used due to its stability, biocompatibility, radiolucency, and elastic modulus. Rare relevant complications were reported, but here, we report two cases of extra-articular migrations of PEEK interference screw from the tibial tunnel after anterior cruciate reconstruction. Case report An 18-year-old boy and a 56-year-old woman underwent anterior cruciate ligament reconstruction using a PEEK interference screw to fix the graft in the tibial tunnel. They suffered from screw extrusion from the tibial tunnel after 40 days and six months, respectively, with an incision rupture or palpable subcutaneous mass. They underwent a second operation and recovered well. Conclusions The exact incidence of extra-articular migrations of PEEK interference screws is unknown, but it seems to be quite low; despite this and its uncertain cause, the negative effects caused by the PEEK material need to be considered.

Proximal hypospadias management involves complex surgical interventions that can lead to the need for long-term specialized care. This review aims to explore the urinary, sexual, and psychosocial outcomes in patients with proximal hypospadias. Patients undergoing surgical correction of proximal hypospadias have generally acceptable urinary flow rates but can still suffer from increased rates of urinary tract infections, voiding difficulties, and leakage as compared to controls. Sexual outcomes of surgical repair closely mimic those of controls. However, a significant proportion of patients report dissatisfaction with their penile appearance after cosmetic surgery. While patients may report hesitancy in approaching sexual or emotional relationships, overall psychosocial outcomes were close to those reports in controls. While still generally very successful, proximal hypospadias surgery has been shown to have more complications in these areas than other milder forms of hypospadias and thus care must be taken to ensure patients are being treated with a holistic mindset throughout their journey.

Background Nicotine is beneficial to mood, arousal and cognition in humans. Due to the importance of cognitive functioning for archery athletes, we investigated the effects of nicotine supplementation on the cognitive abilities, heart rate variability (HRV), and sport performance of professional archers. Methods Eleven college archers were recruited and given 2 mg of nicotine supplementation (NIC group) and placebo (PLA group) in a crossover design. Results The results showed that at 30 min after the intake of nicotine gum, the “correct rejection” time in the NIC group was significantly lower than that of the PLA group (7.29 ± 0.87 vs. 8.23 ± 0.98 msec, p

Cisplatin chemotherapy is standard care for many cancers but is toxic to the kidneys. How this toxicity occurs is uncertain. In this study, we identified apurinic/apyrimidinic endonuclease 2 (APE2) as a critical molecule upregulated in the proximal tubule cells (PTC) following cisplatin-induced nuclear DNA and mitochondrial DNA damage in cisplatin-treated C57B6J mice. The APE2 transgenic mouse phenotype recapitulated the pathophysiological features of C-AKI (acute kidney injury, AKI) in the absence of cisplatin treatment. APE2 pulldown-MS analysis revealed that APE2 binds myosin heavy-Chain 9 (MYH9) protein in mitochondria after cisplatin treatment. Human MYH9-related disorder is caused by mutations in MYH9 that eventually lead to nephritis, macrothrombocytopenia, and deafness, a constellation of symptoms similar to the toxicity profile of cisplatin. Moreover, cisplatin-induced C-AKI was attenuated in APE2-knockout mice. Taken together, these findings suggest that cisplatin promotes AKI development by upregulating APE2, which leads to subsequent MYH9 dysfunction in PTC mitochondria due to an unrelated role of APE2 in DNA damage repair. This postulated mechanism and the availability of an engineered transgenic mouse model based on the mechanism of C-AKI provides an opportunity to identify novel targets for prophylactic treatment of this serious disease. Significance: These results reveal and highlight an unexpected role of APE2 via its interaction with MYH9 and suggest that APE2 has the potential to prevent acute kidney injury in patients with cisplatin-treated cancer.

Dexmedetomidine (Dex) possesses analgesic and anaesthetic values and reported being used in cerebral ischaemic injury therapeutics. Accumulating studies have determined the effect of microRNAs (miRNAs) on the cerebral ischaemic injury. Thus, the present study aimed to unravel the molecular mechanism of miR‐381 and Dex in cerebral ischaemic injury. For this purpose, the cerebral ischaemic injury rat model was established by induction of middle cerebral artery occlusion (MCAO) and expression of miR‐381 and IRF4 was determined. Thereafter, MCAO rats were treated with Dex, miR‐381 mimic, miR‐381 inhibitor and oe‐IRF4 respectively, followed by evaluation of neurological function. Furthermore, neuron cells were isolated from the hippocampus of rats and subjected to oxygen‐glucose deprivation (OGD). Then, OGD‐treated neuron cells and primary neuron cells were examined by gain‐ and loss‐of‐function assay. Neuron cell apoptosis was detected using TUNEL staining and flow cytometry. The correlation between interferon regulatory factor 4 (IRF4) and interleukin (IL)‐9 was detected. Our results showed down‐regulated miR‐38 and up‐regulated IRF4 in MCAO rats. Besides, IRF4 was targeted by miR‐381 in neuron cells. Dex and overexpressed miR‐381, or silenced IRF4 improved the neurological function and inhibited neuron cell apoptosis in MCAO rats. Additionally, in MCAO rats, Dex was found to increase the miR‐381 expression and reduced IRF4 expression to decrease the IL‐9 expression, which suppressed the inflammatory response and cell apoptosis both in vivo and in vitro. Importantly, our study demonstrated that Dex elevated the expression of miR‐381, which ultimately results in the inhibition of inflammation response in rats with cerebral ischaemic injury.

Kimura's disease (KD) is a rare chronic inflammatory disorder that mainly affects young Asian men. It is characterized by subcutaneous mass or nodule in the head and neck region1 . There is no standard treatment for KD.2.

Background Household incense burning is a common ritual behaviour in the Asia-Pacific region but has been associated with inferior developmental outcomes in term infants. We aimed to examine these associations among preterm infants. Methods Information from 1190 mother-infant pairs during six- and eighteen-months follow-up to the Taiwan Birth Cohort Study was examined for associations between household incense burning exposure and infant neurodevelopmental milestone achievement using multivariable Cox proportional hazard model with propensity score weighting, along with stratified, sensitivity and decomposition analysis. Results Household incense burning exposure was associated with delayed gross motor milestone achievement among all preterm infants according to the Cox model and after propensity score weighting. Meanwhile, associations for delayed development were found in gross motor domain milestones among late preterm infants, while fine motor domain delay were found among other preterm infants. Furthermore, the associations between household incense burning status and gross motor milestone delays were attenuated by the interaction between higher education level and household incense burning exposure status. Conclusions Household incense burning exposure was associated with delays, and the motor domains affected differed according to degree of prematurity. These associations were modified by the attenuation upon higher maternal educational status and exposure status interaction.

Schisandra chinensis (Turcz.) Baill., Schisandraceae, is a common Chinese traditional medicine for the treatment of nervous system disorders and cardiovascular diseases. However, little is known about its efficacy in treating gastrointestinal diseases. In the present study, the protective effect of the ethanol extract of S. chinensis against ethanol-induced acute gastric lesions was investigated in mice. Furthermore, we developed a method based on high-performance liquid chromatography for the quantification of bioactive lignans with a dibenzocyclooctadiene skeleton. The ethanol extract of S. chinensis significantly decreased the ulcer index, sheltered mucosa from lesions, increased levels of superoxide dismutase, decreased malondialdehyde levels, and downregulated plasma levels of tumor necrosis factor-α and interleukin-1β. Our findings demonstrated the gastroprotective properties of the ethanol extract of S. chinensis.

We previously reported that intraspinal transplantation of human amniotic mesenchymal stem cells (hAMSCs) promotes functional recovery in a rat model of acute traumatic spinal cord injury (SCI). However, whether intravenous transplantation of hAMSCs also has therapeutic benefit remains uncertain. In this study, we assessed whether intravenous transplantation of hAMSCs improves outcomes in rats with acute traumatic SCI. In addition, the potential mechanisms underlying the possible benefits of this therapy were investigated. Adult female Sprague-Dawley rats were subjected to SCI using a weight drop device, and then hAMSCs or PBS were administered after 2 h via the tail vein. Our results indicated that transplanted hAMSCs could migrate to injured spinal cord lesion. Compared with the control group, hAMSCs transplantation significantly decreased the numbers of ED1 macrophages/microglia and caspase-3 cells, and reduced levels of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6 and IL-1β. In addition, hAMSCs transplantation significantly attenuated Evans blue extravasation, promoted angiogenesis and axonal regeneration. hAMSCs transplantation also significantly improved functional recovery. These results suggest that intravenous administration of hAMSCs provides neuroprotective effects in rats after acute SCI, and could be an alternative therapeutic approach for the treatment of acute SCI.

Cell death after spinal cord ischemia/reperfusion (I/R) can occur through necrosis, apoptosis, and autophagy, resulting in changes to the immune environment. However, the molecular mechanism of this immune regulation is not clear. Accumulating evidence indicates that microRNAs (miRs) play a crucial role in the pathogenesis of spinal cord I/R injury. Here, we hypothesized miR-22-3p may be involved in spinal cord I/R injury by interacting with interferon regulatory factor (IRF) 5. Rat models of spinal cord I/R injury were established by 12-min occlusion of the aortic arch followed by 48-hr reperfusion, with L4-6 segments of spinal cord tissues collected. MiR-22-3p agomir, a lentivirus-delivered siRNA specific for IRF5, or a lentivirus expressing wild-type IRF5 was injected intrathecally to rats with I/R injury to evaluate the effects of miR-22-3p and IRF5 on hindlimb motor function. Macrophages isolated from rats were treated with miR-22-3p mimic or siRNA specific for IRF5 to evaluate their effects on macrophage polarization. The levels of IL-1β and TNF-α in spinal cord tissues were detected by ELISA. miR-22-3p was down-regulated, whereas IRF5 was up-regulated in rat spinal cord tissues following I/R. IRF5 was a target gene of miR-22-3p and could be negatively regulated by miR-22-3p. Silencing IRF5 or over-expressing miR-22-3p relieved inflammation, elevated Tarlov score, and reduced the degree of severity of spinal cord I/R injury. Increased miR-22-3p facilitated M2 polarization of macrophages and inhibited inflammation in tissues by inhibiting IRF5, thereby attenuating spinal cord I/R injury. Taken together, these results demonstrate that increased miR-22-3p can inhibit the progression of spinal cord I/R injury by repressing IRF5 in macrophages, highlighting the discovery of a promising new target for spinal cord I/R injury treatment.

Two key challenges of the PHY-MAC layers of the wireless body area network (i.e., WBAN) are - achieving high system capacity and ensuring secure coexistence. Besides capacity and coexistence, a WBAN PHY (i.e., physical) layer is required to fulfill some preconditions such as it should not impose any detrimental effect on the human health, the network devices must be small enough to be wearable, and it should be suitable for the small area coverage. On the other hand, besides coexistence, the MAC (i.e., Media Access Control) layer needs to ensure service priority, and fairness in resource sharing. Traditionally, the WBAN PHY-MAC is based on 2.4 GHz microwave. However, recently, 60 GHz mmWave based WBAN has been envisioned as a possible solution to the above mentioned challenges. In this paper we have conducted the quantitative comparisons between the 60 GHz and the 2.4 GHz based WBANs. We have also shown the superiority of the 60 GHz based PHY over the 2.4 GHz based PHY grounded on the derived mathematical formulas and simulation results in terms of the system capacity, per cell channel ratio, co-channel reuse ratio, network coverage, device miniaturization, and health issues. Furthermore, we have proposed a game theory based solution for the WBAN MAC layer to ensure coexistence, service priority, and fairness in resource sharing.

Background Caregiver engagement and collaborative team early childhood intervention (ECI) services are international trends; however, relevant evidence of collaborative home-visiting ECI in rural areas is as yet undetermined. Objective The study aimed to investigate the effectiveness of a collaborative ECI program in a rural area of Taiwan. Design The study was a pilot randomized control led trial. Methods Children aged 6 to 33 months experiencing motor delays and their caregivers were enrolled in Taitung, Taiwan. Using stratified randomization, 24 participants were allocated to either experimental or control groups, and both received 5 home visits within 3 months. The experimental group received ECI services based on the International Classification of Functioning, Disability and Health framework and family-centered approaches. The control group received regular home visits by local social workers. Child outcomes included Pediatric Evaluation of Disability Inventory Chinese Version and Peabody Developmental Motor Scale, 2nd edition. Family outcomes included the Disability-Adapted Infant–Toddler version of Home Observation for Measurement, and Chinese versions of the Knowledge of Infant Development Inventory and Parental Stress Index-Short Form. A tester blinded to the study conducted assessments at baseline, postintervention, and 3-month follow-up. Two-way mixed analysis of variance was used with α = .05 (2-tailed). Results The experimental group improved scores on the Disability-Adapted Infant–Toddler version of Home Observation for Measurement significantly more than the control group with an effect size of 0.64 at follow-up. In other outcomes, both groups showed no significant differences. The follow-up rate was 69%, and adherence to the ECI program was acceptable. Limitations A limitation of the study was the heterogeneity of the sample. Conclusions This pilot study revealed possible effectiveness in implementing collaborative ECI programs based on family-centered approaches and the International Classification of Functioning, Disability and Health in rural areas. Larger field studies are needed to confirm our findings.

The 5G networks will see implementation in mHealth in the upcoming years, and it becomes increasingly important to be able to test and develop software for the new generation of hardware. This new generation will likely utilize higher frequency bands in order to be considered 5G. The proposed method of utilizing USRP devices as testbeds should inform researchers of possibilities of emulating new software in real-world environments, to test for various parameters. This article uses other sources to explain the extent of 60 GHz communication capabilities of USRP devices in modern 5G research.

Glioblastoma is the most common malignant brain tumor in central nervous system. Due to absence of the mechanism underlying glioblastoma, the clinical outcome is poor. RNF213 is a ring finger protein and mutation in RNF213 gene is detected in cancers. But the role of RNF213 in glioblastoma is unknown. RNF213 expression was detected by qPCR, western blotting, IHC technology. RNF213 was overexpressed in plasmid pcDNA3.1. Assays including CCK-8, plate colony formation, wound healing, transwell and FITC/PI dye were used to detect cell behaviors. RNF213 was shown to express much lower in tumor tissues and in tumor cell lines compared to control. The patients with higher RNF213 expression displayed longer survival time. When RNF213 was overexpressed in U87MG cells, cell proliferation and colony formation were inhibited significantly. The ability of cell migration and invasion was also suppressed. FAC analysis demonstrated that cell apoptosis was increased after RNF213 overexpression. But cell cycle distribution was not affected by RNF213. Then the expression level of MEKK1, JNK, c-Jun, and cdc42 was decreased after RNF213 overexpression, but increased reversely when RNF213 was knocked down by RNAi technology. RNF213 suppresses carcinogenesis and affects MAPK/JNK signaling pathway in glioblastoma. This study suggests that RNF213 might be a promising target for therapy of glioblastoma.

Purpose This paper aims to propose and test a moderated mediation model examining the relationships among ethical work climate, organizational identification, leader-member-exchange (LMX) and organizational citizenship behavior (OCB). Design/methodology/approach Numerous regression analyses were performed using PROCESS (version 2.13), a macro for SPSS developed by Hayes (2017) to test this moderated mediation model. Findings The analytical results showed that organizational identification mediates the positive relationship between an ethical work climate and OCB. The analytical results also showed that LMX moderates the direct effect of ethical work climate on organizational identification and that LMX also moderates the indirect effect of ethical work climate on OCB via organizational identification. Practical implications This study provides numerous valuable implications for hotels to develop effective strategies to promote employees’ OCB and improve their organizational identification. Originality/value This study was the first attempt to propose and test a moderated mediation model that explores the relationships among ethical work climate, organizational identification, leader-member-exchange (LMX) and OCB.

Background: A role of DNAJC10 has been reported in several cancers, but its function in glioma is not clear. The purpose of this study was to investigate the prognostic role and the underlying functions of DNAJC10 in glioma.Methods: Reverse transcription and quantitative polymerase chain reaction and western blotting were performed to quantify the relative DNAJC10 mRNA and protein expressions of clinical samples. Wilcoxon rank sum tests were used to compare DNAJC10 expression between or among glioma subgroups with different clinicopathological features. The overall survival (OS) rates of glioma patients with different DNAJC10 expression were compared with the Kaplan-Meier method (two-sided log-rank test). The prognosis-predictive accuracy of the DNAJC10 was evaluated by time-dependent receiver operating characteristic (ROC) curves. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations were conducted using the “clusterProfiler” package. Single-sample gene set enrichment analysis was used to estimate immune cell infiltrations and immune-related function levels. The independent prognostic role of DNAJC10 was determined by univariate and multivariate Cox regression analyses. A DNAJC10-based nomogram model was established using multivariate Cox regression in the R package “rms.” Results: Higher DNAJC10 expression was observed in gliomas. It was upregulated in tumors with higher World Health Organization grade, isocitrate dehydrogenase wild-type status, 1p/19q non-co-deletion, and methylguanine-DNA methyltransferase unmethylated gliomas. Patients with gliomas with higher DNAJC10 expression had poorer prognoses than those with low-DNAJC10 gliomas. The predictive accuracy of 1/3/5-year OS of DNAJC10 was stable and robust using a time-dependent ROC model. Functional enrichment analysis recognized that T cell activation and T cell receptor signaling were enriched in higher DNAJC10 gliomas. Immune cell and stromal cell infiltrations, tumor mutation burden, copy number alteration burden, and immune checkpoint genes were also positively correlated with glioma DNAJC10 expression. A DNAJ10-based nomogram model was established and showed strong prognosis-predictive ability.Conclusion: Higher DNAJC10 expression correlates with poor prognosis of patients with glioma and is a potential and useful prognostic biomarker.

BACKGROUND Social function and quality of life were negatively impacted by the sequelae of treatment for the disease in the head and neck cancer survivor with swallowing disorder. METHOD Data from a total of 1023 survivors between July 2012 and November 2017 were collected from the Taiwan Data Bank of Persons with Disability. Nonparametric rank F test was used to analyze the influence of different variables on social participation. RESULTS (a) All WHODAS (World Health Organization Disability Assessment Schedule) 2.0 scores revealed significantly increased difficulty when swallowing impairment increased (P

On the Internet platform, we can use big data mining technology to obtain rich teaching resources, assist classroom teaching, and change the previous relatively single word teaching content. When carrying out English word teaching, we should not only use textbooks to design courseware, but actively collect data resources such as pictures related to word teaching, and use these resources in courseware making to attract students' attention. In this paper, an intelligent recommendation system for English vocabulary learning is designed by using the intelligent recommendation model for English vocabulary learning. The function of uploading corpus is added to realize the automatic updating of the vocabulary. Integrate and update the learner ability model and learning style model, realize the accurate description of user groups, and improve the efficiency of system resource recommendation. Through static acquisition and dynamic mining method to obtain the basic information and behavior interaction data of users, form the characteristics of learners, infer the ability and learning style of learners through machine learning algorithm, improve the effectiveness of teaching and mobilize students' interest in learning.

Objective: Early identification for the need of tracheostomy (TT) in aneurysmal subarachnoid hemorrhage (aSAH) patients remains one of the main challenges in clinical practice. Our study aimed to establish and validate a nomogram model for predicting postoperative TT in aSAH patients.Methods: Patients with aSAH receiving active treatment (interventional embolization or clipping) in our institution between June 2012 and December 2018 were retrospectively included. The effects of patients' baseline information, aneurysm features, and surgical factors on the occurrence of postoperative TT were investigated for establishing a nomogram in the training cohort with 393 patients. External validation for the nomogram was performed in the validation cohort with 242 patients.Results: After multivariate analysis, higher age, high neutrophil-to-lymphocyte ratio (NLR), high World Federation of Neurological Surgeons Scale (WFNS), and high Barrow Neurological Institute (BNI) grade were left in the final logistic regression model. The predictive power of the model was excellent in both training cohort and validation cohort [area under the curve (AUC): 0.924, 95% confidence interval [CI]: 0.893–0.948; AUC: 0.881, 95% CI: 0.833–0.919]. A nomogram consisting of these factors had a C-index of 0.924 (95% CI: 0.869–0.979) in the training cohort and was validated in the validation cohort (C-index: 0.881, 95% CI: 0.812–0.950). The calibration curves suggested good match between prediction and observation in both training and validation cohorts.Conclusion: Our study established and validated a nomogram model for predicting postoperative TT in aSAH patients.

To evaluate the value of serum Lactate Dehydrogenase (LDH) level in predicting recurrence and the overall survival (OS) of glioma patients.A total number of 216 patients with glioma in our institution were retrospectively recruited to analyze the relationship between preoperative serum LDH level and prognosis.Overall, the median age of patients was 46.0 (31.0-57.0) years old; 53.7% (116 of 216) of the enrolled patients were male. Multivariate analysis revealed that serum LDH level (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.96-0.98, P 0.001) and World Health Organization (WHO) grade (grade II: OR = 19.64, 95%CI = 5.56-69.35, P 0.001; grade III: OR =1 9.50, 95%CI = 7.08-53.73, P 0.001; grade IV: OR = 15.23, 95%CI = 4.94-46.97, P 0.001) were significant and independent of 1-year Progression-free survival (PFS) after adjusting for confounders. The predictive performance of serum LDH level was represented with area under curve (AUC) = 0.741, 95%CI = 0.677-0.798. Multivariate Cox analysis revealed that LDH level (hazard ratio [HR] = 2.56, 95%CI = 1.59-4.15, P 0.001) and WHO grade (grade II: HR = 4.58, 95%CI = 0.56-37.23, P = 0.155; grade III: HR = 16.35, 95%CI = 2.16-123.80, P = 0.007; grade IV: HR = 42.13, 95%CI = 5.83-304.47, P 0.001) remained associated with survival at 2-year follow-up. At 3-year follow-up, lymphocyte count (HR = 0.68, 95%CI = 0.51-0.91, P = 0.008), LDH level (HR = 2.21, 95%CI = 1.40-3.49, P = 0.001), and WHO grade (grade II: HR = 1.44, 95%CI = 0.44-4.68, P = 0.543; grade III: HR = 4.99, 95%CI = 1.68-14.87, P = 0.004; grade IV: HR = 16.96, 95%CI = 6.13-46.93, P 0.001) remained associated with survival in multivariate Cox analysis.Our study demonstrated that preoperative serum LDH level could serve as a reliable indicator for predicting prognosis of glioma patients. Further multicenter studies are still required to verify our findings.

Objective To investigate the correlation between acetylcholine receptor antibodies (AChR‐Ab) concentration levels and individualized clinical symptoms in patients with AChR myasthenia gravis (AChR‐MG) in China. Methods ELISA was used to determine the concentration of AChR‐Ab in patients with MG. The Myasthenia Gravis Foundation of America (MGFA) Clinical Classification, Quantitative Myasthenia Gravis (QMG) score, and MG‐specific activities of daily living (MG‐ADL) scoring systems were used to evaluate the clinical status of patients. Spearman correlation analysis was used to determine the correlation between the AChR‐Ab concentration and clinical score. The changes in the antibody concentration and clinical score are shown in MGFA‐antibody concentration–treatment plots. Results Autoantibody detection tests were performed in 67 patients, and their clinical scores were recorded. Forty‐nine patients received immunosuppressive therapy, 17 patients received pyridostigmine only, and 1 patient under thymectomy without any medication. The AChR‐Ab concentration correlated with the MGFA Classification in 5 (29.4%) patients in the pyridostigmine‐only group and 15 (30.6%) patients in the immunosuppressive drug group. The changes in the MGFA Classification preceded the changes in the AChR‐Ab concentration in 4 (23.5%) patients treated with pyridostigmine and 10 (20.4%) patients on immunosuppressive drugs. In patients on oral non‐steroidal immunosuppressants, the AChR‐Ab concentration changed by more than 50%, whereas the MGFA Classification did not increase. The AChR‐Ab concentration decreased in 17/32 (53.1%) patients after thymectomy, and then increased, whereas the AChR‐Ab concentration increased in 15/32 (46.9%) patients and the MGFA Classification decreased in 27/32 (81.8%) patients after thymectomy. The AChR‐Ab concentration presented a slight correlation with the corresponding MGFA, QMG, and MG‐ADL in patients with thymoma. Discussion In the Chinese AChR‐MG population, the Changes in the AChR‐Ab concentration in individuals with AChR‐MG did not consistently correlate with the severity of clinical symptoms., We detected AChR‐Ab concentration at least four times per patient and performed corresponding clinical evaluations on 67 patients, and MGFA‐antibody concentration–treatment plots were drawn for each patient. We found that patients receiving oral glucocorticoid doses greater than 40 mg/d and nonsteroidal immunosuppressive drugs may have increased or decreased AChR‐Ab concentrations, and the clinical symptoms often improved to varying degrees. We did not find a consistent correlation between the changes in individual AChR‐Ab concentrations and the severity of clinical symptoms in patients.

(1) Background: Busulfan has been used as a conditioning regimen in allogeneic hematopoietic cell stem transplantation (HSCT). Owing to a large inter-individual variation in pharmacokinetics, therapeutic drug monitoring (TDM)-guided busulfan dosing is necessary to reduce graft failure and relapse rate. As there exists no TDM of busulfan administration for HCT in Taiwan, we conducted a pilot study to assess the TDM-dosing of busulfan in the Taiwanese population, (2) Methods: Seven patients with HCT from The Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan, received conditioning regimens consisting of intravenous busulfan and other chemotherapies. After the initial busulfan dose, blood samples were collected for busulfan TDM at 5 min, 1 h, 2 h, and 3 h. Busulfan was extracted and detected by performing stable-isotope dilution LC–MS/MS. Plasma busulfan concentration was quantified and used for dose adjustment. Potential adverse effects of busulfan, such as mucositis and hepatic veno-occlusive disease (VOD), were also evaluated, (3) Results: The LC–MS/MS method was validated with an analyte recovery of 88–99%, within-run and between-run precision of &lt, 15%, and linearity ranging from 10 to 10,000 ng/mL. Using TDM-guided busulfan dosing, dose adjustment was necessary and performed in six out of seven patients (86%) with successful engraftments in all patients (100%). Mild mucositis was observed, and VOD was diagnosed in only one patient, (4) Conclusions: This single-center study in Taiwan demonstrated the importance of busulfan TDM in increasing the success rate of HCT transplantation. It is also necessary to further investigate the optimal busulfan target value in the Taiwanese population in the future.

Replacement of topsoil to an appropriate depth is one of the key methods for ecological restoration. The objective of this study was to investigate the effects of topsoil replacement depth on vegetation and soil properties, and to identify the optimum soil depth for reclamation of coal mine spoils in a cold alpine mining area. We sowed 3 herbaceous species after coal mine spoil heaps were treated with topsoil to 3 depths (0, 20‒25, 40‒45 cm). The variations in vegetation community structure, plant growth, soil properties were measured at different replaced topsoil depths. The correlations between plant and soil properties were analyzed statistically. The results showed species richness, diversity and evenness were not significantly different among different depths of topsoil (P > 0.05). Vegetation coverage, density, height and aboveground biomass increased significantly (P < 0.05) with increasing topsoil depth. Soil properties did not change significantly with increasing topsoil depth (P > 0.05), but soil organic matter was significantly higher at 40‒45 cm topsoil depth than at other two depths (P < 0.05). All soil properties, with the exception of total potassium, were positively correlated with the plant growth parameters. The 40‒45 cm topsoil depth of replacement should be considered as effective method in reclaiming coal mine spoils. The use of both topsoil replacement to a depth of 40‒45 cm and sowing of suitable herbaceous seeds is found to be an effective restoration strategy. Additionally, fertilization might be used as a substitute for artificial topsoil replacement to improve soil quality and speed up revegetation process by the positive plant-soil interactions.

BACKGROUND In general, malignant tumors metastasize to the pancreas in < 1% of cases. Most patients miss the opportunity for further surgery due to distant metastases; however, for fibrosarcomas, aggressive surgery may be helpful even if distant metastases occur. Hence, we report such a case and share some valuable information about the disease. CASE SUMMARY A 45-year-old man was admitted with recurrent epigastric pain for 10 days. The abdominal pain was mainly related to bloating with nausea, but no other associated symptoms. No particular signs were found on abdominal examination or laboratory testing. In 2003, a local distal expanded resection of the primary fibrosarcoma in the left chest wall was performed. Then, a left pneumonectomy was performed in 2017 due to diffuse metastases from the fibrosarcoma to the left lung. Enhanced computed tomography (CT) and magnetic resonance imaging of the upper abdomen suggested multiple masses of different sizes involving the head and tail of the pancreas; no local lymph node enlargement was noted. The postoperative pathologic diagnosis revealed a fibrosarcoma of the pancreas. A CT re-examination 6 mo postoperatively showed no local recurrence or distant metastases. CONCLUSION A fibrosarcoma is a rare low-grade malignant tumor, and metastases to the pancreas are even rarer. Patients with a history of a fibrosarcoma should consider the possibility of metastasis when a pancreatic neoplasm is demonstrated. Surgical resection is the preferred treatment.

Objective Some lines of evidence show that D2/D3 receptor partial agonist pramipexole may be effective in the treatment of extrapyramidal symptoms (EPS) and psychiatric symptoms of schizophrenia. Therefore, we analyzed whether a low dose of pramipexole (0.375-0.75 mg/day) has efficacy on EPS and symptoms of schizophrenia while maintaining tolerability. Methods Ten subjects with EPS [including drug-induced parkinsonism (DIP) and akathisia] were recruited in a stage-1, open-label pilot study. All the subjects were treated with a low dose of pramipexole. The evaluations were performed at baseline, day 3, week 1, week 2, week 4, week 6, and week 8. The ratings of SAS, BARS, PANSS, CDSS, and CGI-S and adverse effects (AE) were recorded in every visit. Results SAS total scores decreased significantly during the study in patients with DIP (P

The rapid growth of Internet of Vehicles (IoV) has brought huge challenges for large data storage, intelligent management, and information security for the entire system. The traditional centralized management approach for IoV faces the difficulty in dealing with real-time response. The blockchain, as an effective technology for decentralized distributed storage and security management, has already showed great advantages in its application of Bitcoin. In this paper, we investigate how the blockchain technology could be extended to the application of vehicle networking, especially with the consideration of the distributed and secure storage of big data. We define several types of nodes such as vehicle and roadside for vehicle networks and form several sub-blockchain networks. In this paper, we present a model of the outward transmission of vehicle blockchain data, and then give detail theoretical analysis and numerical results. This paper has shown the potential to guide the application of blockchain for future vehicle networking.

Gateways play very important roles in smart homes. With gateways that can effectively separate applications and physical devices, the smart home architecture can be simplified. In the future, when more and more wireless devices are deployed in smart homes, gateways are facing critical challenges to accommodate the variety and heterogeneity of devices while maintaining enough simplicity, full interoperability, high energy and spectrum efficiency, and uncompromised system security. In this article, we first study the-state-of-the-art techniques and solutions for smart home infrastructure and present both their advantages and disadvantages. Then we propose a data-centric cognitive gateway, which is simple, efficient, and secure for smart homes. In addition, we investigate the trade-off among deployment cost, routine maintenance overhead, and system security. Our experiments verify the efficiency of our proposed solutions.

Recent advancements in wireless technology have tested Wireless Balloon Networks (WBNs) as an ideal solution for the provision of internet facilities in deprived and challenging areas. A few high profile companies, such as Google, Space Data Inc., etc., have already made news by initiating projects based on high-altitude WBNs in order to provide internet facilities in remote areas. Unfortunately, the technical details have mainly been kept confidential so far. In this paper, we attempt to analyze the percolation properties of large-scale WBNs, considering both homogenous and heterogenous wireless nodes. In order to do so, we modeled a WBN as a large-scale random network where the path-loss models of homogenous and heterogenous WBNs were reduced to GDM (Gilbert's Disk Model) and RGDM (Random Gilbert's Disk Model), respectively. The bounds of the critical density regime were derived for both percolation models. Additionally, this paper implemented an experimental test bed for the WBN percolation model. Consequently, the findings of this research may prove crucial in estimating critical network properties. Keywords: Percolation, Connectivity, WBN, PPP, GDM

Little is known about the changes of people with schizophrenia disability in Taiwan who receive routine treatments under the current mental healthcare system. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess and track changes in the degree of disability in people with schizophrenia before and after 4 years of follow-up. Data on 4497 people with schizophrenia were acquired from the Taiwan Data Bank of Persons with Disability. The WHODAS 2.0 was used for disability assessment, and the chi-square test, logistic regression and generalised estimating equations were adopted for statistical analysis. People with schizophrenia exhibited improvement in cognition, mobility and participation among the six domains as well as in the overall score. The degree of disability in all domains remained mild to moderate among people aged 18-64 years; the degree of disability in cognition declined from moderate to severe among patients aged ≥65 years. The degree of disability in all domains remained mild to moderate among people with mild to moderate impairment; among those with severe impairment, the degree of disability in the domains of cognition and life activities declined from moderate to severe and the degree of disability in the domain of mobility declined from mild to moderate. Community-dwelling patients exhibited less degree of disability in all domains than their institutionalised peers. Early detection and treatment and an emphasis on communication and social problem-solving skills in rehabilitation programmes are recommended for people with schizophrenia.

Aims High glucose (HG)-induced pancreatic β-cell apoptosis may be a major contributor to the progression of diabetes mellitus (DM). NADPH oxidase (NOX2) has been considered a crucial regulator in β-cell apoptosis. This study was designed to evaluate the impact of GLP-1 receptor agonist (GLP-1Ra) liraglutide on pancreatic β-cell apoptosis in diabetes and the underlying mechanisms involved. Methods The diabetic rat models induced by streptozotocin (STZ) and a high fat diet (HFD) received 12 weeks of liraglutide treatment. Hyperglycemic clamp test was carried out to evaluate β-cell function in vivo. Flow cytometry analysis was used to measure apoptosis rates in vitro. DCFH-DA method was used to detected ROS level in vivo and in vitro. Results Liraglutide significantly improved islet function and morphology in diabetic rats and decreased cell apoptosis rates. Thr183/Thr185 p-JNK1/2 and NOX2 levels reduced in diabetic rats and HG-induced INS-1 cell following liraglutide treatment. In addition, liraglutide upregulated the phosphorylation of AMPKα (p-AMPKα), which prevented NOX2 activation and alleviated HG-induced β-cell apoptosis. Conclusion The p-AMPKα/NOX2/JNK1/2 pathway is essential for liraglutide to attenuate HG-induced β-cell apoptosis, which further proves that GLP-1Ras may become promising therapeutics for diabetes mellitus.

Rotational malalignment between the femoral and tibial components in total knee arthroplasty (TKA) can affect clinical outcomes, but there is no consensus on how to best determine tibia tray orientation. The posterolateral corner-locked (PLCL) technique may be a new method. This study aims to assess the applicability of this technique in a Chinese population. Forty normal Chinese volunteers were recruited and underwent computed tomography (CT) of the lower limbs. Knee model reconstructions and simulated standard tibial osteotomy were conducted digitally. The transepicondylar axis (TEA), the Akagi line, and the line connecting the medial third of the tibial tubercle with the midpoint of the posterior cruciate ligament (PCL) were projected to the tibial cross-section and marked. The PLCL technique was applied using either symmetrical or asymmetrical tibial tray templates, and the anteroposterior (AP) axis of the tibial tray was marked. The angles between the TEA and these lines were calculated, and the statistical differences were analyzed. The angle between the TEA and the Akagi line and between the TEA and the line connecting the medial third of the tibial tubercle with the midpoint of the PCL were 96.90 ± 5.57 and 107.31 ± 5.95 degrees, respectively. The angles between the TEA and the AP axis of the symmetrical and the asymmetrical design tibial trays were 94.01 ± 4.21 and 96.65 ± 4.70 degrees, respectively. Except for the Akagi line and AP axis of the asymmetrical tibial tray, statistical differences were found between all lines (p

Photovoltaic cells based on halide perovskites, possessing remarkably high power conversion efficiencies have been reported. To push the development of such devices further, a comprehensive and reliable understanding of their electronic properties is essential but presently not available. To provide a solid foundation for understanding the electronic properties of polycrystalline thin films, we employ single-crystal band structure data from angle-resolved photoemission measurements. For two prototypical perovskites (CH3NH3PbBr3 and CH3NH3PbI3), we reveal the band dispersion in two high-symmetry directions and identify the global valence band maxima. With these benchmark data, we construct "standard" photoemission spectra from polycrystalline thin film samples and resolve challenges discussed in the literature for determining the valence band onset with high reliability. Within the framework laid out here, the consistency of relating the energy level alignment in perovskite-based photovoltaic and optoelectronic devices with their functional parameters is substantially enhanced.

Advancements in miniaturized electronics and smart sensors combined with a broad platform of smart phones, big data, cloud service, and wireless communication have not only empowered wearable technology, they have also increased users life expectancy. For example, a wearable system provides unobtrusive ambulatory, continuous, ubiquitous health measurement, and real-time solution for patients physical without hampering the natural movement of the wearer. However, the ability to measure one’s Autonomic Nervous System (ANS) using wearable biosensors in healthcare applications has been limited due to several challenges related to a lack in wearability, accuracy, reliability, and low-power consumption. In this paper, we presented a novel wearable ring sensor for the continuous measurement of four ANS activities: 1) electrodermal activity; 2) heart rate; 3) skin temperature; and 4) locomotion. Detailed information is given regarding the development of the proposed ring sensor followed by a discussion of the evaluation that was done utilizing the wearable sensor on volunteers to gather data. Specifically, volunteers wore the ring sensor while being simultaneously monitored with real-time telemetry, the sensor values are processed and analyzed. This paper is a continuation and extension of earlier work by the authors. New validation, experimental results, and development of the mobile application have been added to improve the previous system. The experiment demonstrated accurate results, and data were collected from 43 participants of diverse age, body mass, height, and race. Additionally, to evaluate the performance of the developed ring sensor, we compared the results with a state-of-the-art open source device. This paper aims to improve the worn biomedical sensor market, specifically when it comes to size and accuracy of worn sensors.

Background: Previous studies suggest S100A9 is a promising biomarker for prognosis in cancer, including hepatocellular carcinoma (HCC). We examined the utility of serum S100A9 in predicting prognosis in HCC after curative resection. Methods: We conducted a retrospective study of 379 HCC patients who underwent curative resection. Patients were randomly stratified into two independent groups to evaluate the prognostic value of S100A9. S100A9 was determined by ELISA. Results: Patients with advanced disease showed significantly higher S100A9 levels (all P < 0.050). Serum S100A9 was elevated in patients who developed recurrence and death in both training and validation cohorts (all P < 0.050). In the training cohort, patients with higher preoperative S100A9 had a significantly shorter time to recurrence (15.50 vs. 64.00 months, P < 0.001) and decreased overall survival (34.80 months vs. not reached, P < 0.001). Cox regression demonstrated S100A9 was an independent indicator for poor prognosis after resection (both P < 0.050). These results were confirmed by the independent validation cohort. Conclusions: Serum S100A9 is associated with dismal outcomes in HCC patients and can serve as a novel prognostic indicator for HCC patients after resection. Determination of S100A9 might help tailor treatment strategy to improve HCC patient prognosis.

Intestinal Behçet's syndrome (IBS) has high morbidity and mortality rates with serious complications. The purpose of this study was to investigate the expression of pyroptosis-related proteins in the intestinal tissues of IBS patients and explore the role of plasma exosomes derived from IBS patients in the pyroptosis of intestinal epithelial cells.Immunohistochemistry was used to investigate the expression of nucleotide-binding domain-like receptor protein 3 (NLRP3), caspase-1, and gasdermin D (GSDMD). Quantitative real-time PCR was employed to measure the mRNA levels of IL-1β and IL-18 in the intestinal tissues. Plasma exosomes were isolated and observed by transmission electron microscopy. The exosomes were co-cultured with intestinal epithelial cells in vitro. Western blot was used to measure the expression of pyroptosis-related proteins including NLRP3, full-length GSDMD, N-terminal GSDMD, pro-caspase-1, and cleaved caspase-1. The levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay. Cell death was measured by using the lactate dehydrogenase (LDH) release assay.Expression of NLRP3 (12.2% ± 1.2%, 8.1% ± 0.9%, t = 4.692, p = 0.009), caspase-1 (24.6% ± 2.1%, 4.2% ± 1.8%, t = 12.842, p = 0.000), and GSDMD (16.6% ± 1.9%, 9.8% ± 1.3%, t = 5.194, p = 0.007) were significantly increased in the intestinal tissues of patients with IBS compared with normal control (NC) group, respectively. The relative mRNA levels of IL-1β (t = 4.308, p = 0.005) and IL-18 (t = 3.096, p = 0.021) in the intestinal tissues were significantly higher in IBS patients than in NC group, while the protein levels of IL-1β (t = 3.873, p = 0.018) and IL-18 (t = 4.389, p = 0.012) were also significantly increased, which was consistent with the results of the relative mRNA levels. Moreover, we found that exosomes from IBS patients significantly induced pyroptosis of intestinal epithelial cells via the activation of NLRP3 inflammasome in vitro experiments.Plasma exosomes derived from IBS patients may induce pyroptosis of intestinal epithelial cells via the activation of NLRP3 inflammasome. Key Points •The role of exosomes in IBS is first reported in this study. • In this study, we explored the mechanism that plasma exosomes derived from IBS patients may induce pyroptosis of intestinal epithelial cells via the activation of NLRP3 inflammasome.

Spinal cord ischemia-reperfusion (SCIR) injury is a serious complication of open surgical and endovascular aortic procedures. MicroRNA-132-3p (miR-132-3p) has been reported to be involved in the progression of various diseases, but its role in SCIR injury is unclear. Thus, we aimed in this study to investigate the mechanism of miR-132-3p in SCIR injury and explore its pathway as a therapeutic target for SCIR injury. We first constructed a SCIR injury rat model and documented motor function in the model. Reverse transcription quantitative polymerase chain reaction (RT-qPC)R and Western blot analysis were used to detect the expression of miR-132-3p and mitogen-activated protein kinase kinase kinase 3 (MEKK3) in SCIR injury rats. The interaction between miR-132-3p and MEKK3 was identified by dual-luciferase reporter gene assay. Then, the effects of miR-132-3p and MEKK3 on macrophage M1 polarization were evaluated in vitro and in vivo by altering their expression in macrophages of SCIR injury rats, with treatments altering the nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)/p38 signaling pathways using SP600125, SB203580, or PDTC. The SCIR injury rats had a high Tarlov score and low miR-132-3p expression along with high MEKK3 expression. miR-132-3p could directly bind to MEKK3, and that macrophage M1 polarization and inflammation could be inhibited by overexpression of miR-132-3p through downregulating MEKK3 and inactivating the NF-κB and p38/JNK signaling pathways. Besides, increased miR-132-3p expression could decrease the injured rat Tarlov score. Overall, our study demonstrated that miR-132-3p can suppress M1 polarization of macrophages and alleviate SCIR injury by blocking the MEKK3-dependent activation of the NF-κB and p38/JNK signaling pathway. Thus, miR-132-3p and its downstream pathways may be useful targets to alleviate the symptoms of SCIR injury.

BackgroundCD40 agonist immunotherapy can potentially license antigen-presenting cells to promote antitumor T-cell activation and re-educate macrophages to destroy tumor stroma. Systemic administration of CD40 agonists has historically been associated with considerable toxicity, providing the rationale for development of tumor-targeted immunomodulators to improve clinical safety and efficacy. This phase I study assessed the safety, tolerability, preliminary antitumor activity, and preliminary biomarkers of ABBV-428, a first-in-class, mesothelin-targeted, bispecific antibody designed for tumor microenvironment-dependent CD40 activation with limited systemic toxicity.MethodsABBV-428 was administered intravenously every 2 weeks to patients with advanced solid tumors. An accelerated titration (starting at a 0.01 mg/kg dose) and a 3+3 dose escalation scheme were used, followed by recommended phase II dose cohort expansions in ovarian cancer and mesothelioma, tumor types associated with high mesothelin expression.ResultsFifty-nine patients were treated at doses between 0.01 and 3.6 mg/kg. The maximum tolerated dose was not reached, and 3.6 mg/kg was selected as the recommended phase II dose. Seven patients (12%) reported infusion-related reactions. Treatment-related grade ≥3 treatment-emergent adverse events were pericardial effusion, colitis, infusion-related reaction, and pleural effusion (n=1 each, 2%), with no cytokine release syndrome reported. The pharmacokinetic profile demonstrated roughly dose-proportional increases in exposure from 0.4 to 3.6 mg/kg. Best response was stable disease in 9/25 patients (36%) treated at the recommended phase II dose. CD40 receptor occupancy >90% was observed on peripheral B-cells starting from 0.8 mg/kg; however, no consistent changes from baseline in intratumoral CD8+ T-cells, programmed death ligand-1 (PD-L1+) cells, or immune-related gene expression were detected post-ABBV-428 treatment (cycle 2, day 1). Mesothelin membrane staining showed greater correlation with progression-free survival in ovarian cancer and mesothelioma than in the broader dose escalation population.ConclusionsABBV-428 monotherapy exhibited dose-proportional pharmacokinetics and an acceptable safety profile, particularly for toxicities characteristic of CD40 agonism, illustrating that utilization of a tumor-targeted, bispecific antibody can improve the safety of CD40 agonism as a therapeutic approach. ABBV-428 monotherapy had minimal clinical activity in dose escalation and in a small expansion cohort of patients with advanced mesothelioma or ovarian cancer.Trial registration numberNCT02955251.