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This study aimed to develop and validate a novel nomogram to predict the risk of non-infectious fever (NIF) in patients following laparoscopic myomectomy. A retrospective analysis was conducted on data from patients who underwent laparoscopic myomectomy between 2019 and 2023. Pertinent variables before, during, and after surgery were collected. Multivariate logistic regression analysis identified independent risk factors for postoperative NIF, from which a nomogram was constructed. The study included 576 patients, among whom 64 (11.1%) developed postoperative NIF. Multivariate analysis identified leiomyoma size, number of leiomyomas, preoperative hemoglobin levels, operative time, and estimated blood loss as independent risk factors for postoperative NIF. A predictive nomogram model incorporating these factors demonstrated good accuracy following internal validation. The developed nomogram represents the first tool tailored for predicting NIF after laparoscopic myomectomy. Its implementation can assist clinicians in early identification of high-risk patients, facilitating timely preventive and management strategies., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: We aimed to describe jaw function characteristics in patients with anterior disc displacement without reduction (ADDWoR) using the jaw function limitation scale (JFLS), and to investigate the effects of biopsychosocial risk factors on limited jaw function., Design: In this cross-sectional study of 636 patients with ADDWoR (females, 568; males, 68), we used the JFLS to assess jaw function. Behavioral, psychological, sociodemographic, and biomedical data were collected. Multivariate logistic regression analysis was used to determine risk factors affecting limited jaw function. A receiver operating characteristic curve was used to evaluate the predictive effect of these risk factors., Results: ADDWoR-associated limitations included restricted jaw mobility and mastication, which exceeded median global functional limitations scale scores, especially mouth opening to bite an apple and chewing tough food. Females had greater limitations in jaw mobility, verbal and emotional communication, and overall. Multivariate logistic regression analysis findings indicated that oral behaviors, anxiety, sex, pain intensity, and maximal mouth opening (MMO) were predictive of limited jaw function (area under the curve, 72 %)., Conclusion: Patients with ADDWoR reported mastication and jaw mobility restrictions, with females having more pronounced limitations, and specific risk factors identified as significant predictors of jaw function limitations. Along with pain relief and improvement in MMO, appropriate psychological counseling and oral behavioral correction facilitates recovery of jaw function in such patients., Competing Interests: Declaration of Competing Interest The authors state that they have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Risk factors for temporomandibular disorder (TMD) pain remain unclear., Objectives: This study aimed to identify risk factors for TMD pain using a biopsychosocial model and to investigate interactions between potential risk factors-oral behaviours (OBs), psychological factors and sleep quality-and their direct and indirect effects on TMD pain., Methods: This was a cross-sectional study of 488 patients with TMDs (422 women; 30.8 ± 9.4 years). Pain was assessed using the Numerical Rating Scale. Demographic, behavioural, psychological and biomedical data were collected through clinical examination, face-to-face interviews and questionnaires. Multiple linear regression analysis was used to identify factors associated with TMD pain. Mediation and moderation analysis were used to evaluate interactions between variables. Significant mediation ('0' not included in the 95% confidence interval (CI)) and moderation (p < .05) effects on TMD pain were identified., Results: Marital status, diagnosis subgroup, previous medication use, depression and sleep quality were significant risk factors for TMD pain (p < .05). Significant mediation effects were observed as follows: depression and sleep quality mediated the association between OBs and pain; sleep quality mediated the association between somatization, depression, anxiety and pain; and depression mediated the association between sleep quality and pain (all 95% CI did not contain '0')., Conclusions: (1) Marital status, diagnosis subgroup, previous medication use, depression and sleep quality were associated with TMD pain. (2) OBs can exacerbate pain by promoting depression and reducing sleep quality. Psychological factors and sleep quality can interact to exacerbate pain., (© 2024 John Wiley & Sons Ltd.)

The lacking of stable and susceptible cell lines has hampered research on pathogenic mechanism of crustacean white spot syndrome virus (WSSV). To look for the suitable cell line which can sustain WSSV infection, we performed the studies on WSSV infection in the Spodoptera frugiperda (Sf9) insect cells. In consistent with our previous study in vitro in crayfish hematopoietic tissue cells, the WSSV envelope was detached from nucleocapsid around 2 hpi in Sf9 cells, which was accompanied with the cytoplasmic transport of nucleocapsid toward the cell nucleus within 3 hpi. Furthermore, the expression profile of both gene and protein of WSSV was determined in Sf9 cells after viral infection, in which a viral immediate early gene IE1 and an envelope protein VP28 exhibited gradually increased presence from 3 to 24 hpi. Similarly, the significant increase of WSSV genome replication was found at 3-48 hpi in Sf9 cells after infection with WSSV, indicating that Sf9 cells supported WSSV genome replication. Unfortunately, no assembled progeny virion was observed at 24 and 48 hpi in Sf9 cell nuclei as determined by transmission electron microscope, suggesting that WSSV progeny could not be assembled in Sf9 cell line as the viral structural proteins could not be transported into cell nuclei. Collectively, these findings provide a cell model for comparative analysis of WSSV infection mechanism with crustacean cells., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients., Methods: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias., Results: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001)., Conclusions: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285)., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Breast cancer is a major public health concern. Proteomics enables identification of proteins with aberrant properties. Here, we identified proteins with abnormal expression levels in breast cancer tissues and systematically analyzed and validated the data to locate potential diagnostic and therapeutic targets., Methods: Protein expression level in breast cancer tissues and para-carcinoma tissues were detected by Isobaric Tags for Relative and Absolute Quantification (iTRAQ) technology and further screened through Gene Expression Profiling Interactive Analysis (GEPIA) database. Cellular components, protein domain and Reactome pathway analysis were performed to screen functional targets. Abnormal expression levels of functional targets were validated by Oncomine database, quantitative real time polymerase chain reaction (qRT-PCR) and proteomics detection. Protein correlation analysis was performed to explain the abnormal expression levels of potential targets in breast cancer., Results: Overall, 207 and 207 proteins were up- and down-regulated, respectively, in breast cancer tissues, and approximately 50% were also detected in the GEPIA database. The overlapping proteins were mainly extracellular proteins containing epidermal growth factor-like domain in leukocyte adhesion molecule (EGF-Lam) domain and enriched in laminin interaction pathway. Moreover, the downregulated laminin interaction proteins could be functional targets, which were also validated through Oncomine-Richardson and Oncomine-Curtis database. However, the lower expression level of laminin interaction proteins only fit for luminal breast cancer cells with no or low metastasis ability because the proteins achieved higher expression level in more invasive claudin-low breast cancer cells. In addition, when compared with corresponding in situ carcinoma tissues, above-mentioned proteins also showed higher expression levels in invasive carcinoma tissues. Finally, we have revealed the negative correlation between the laminin interaction proteins and the claudins., Conclusions: The laminin interaction protein, especially for laminins with β1 and γ1 subunits and their integrin receptors with α1 and α6 subunits, showed lower expression levels in luminal breast cancer with no or lower metastatic ability, but showed higher expression levels in claudin-low breast cancer with higher metastatic ability; and their higher expression could be related to the low claudin expression., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2214/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

The study aimed to compare the efficacy of platelet-rich plasma (PRP) injections for the treatment of temporomandibular joint osteoarthritis (TMJ-OA) with hyaluronic acid (HA) therapy. This randomized controlled trial included 70 patients with TMJ-OA, randomly divided into either a PRP or HA group. The pain intensity, maximum mouth opening (MMO), TMJ sound score, and proportion of crepitus were recorded and compared at baseline and at 1, 3, and 6 months. Both groups showed statistically significant improvements in pain intensity, MMO, TMJ sound, and scale scores during the 6-month follow-up period. The improvements in pain intensity during mouth opening at 1 month, MMO at 1, 3, and 6 months, TMJ sound score at 1 and 3 months, and GAD-7 score at 6 months in the PRP group were greater than in the HA group (p < 0.05). Compared with the HA group, imaging improvement in the PRP group was also higher (p < 0.05). Within the limitations of the study it seems that the application of PRP therapy in TMJ-OA is should be considered whenever possible., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the relation between the expression of PD-1, PD-L1, CD3, CD8, Foxp3 and clinicopathological features in patients with oral leukoplakia (OLK) and oral squamous cell carcinomas (OSCC) as well as the malignant outcome in OLK patients, and to study the effect of PD-1 and PD-L1 on immune microenvironment in the progression of oral carcinogenesis., Methods: We evaluated the expression of PD-1/PD-L1 and composition of CD3 + , CD8 + and Foxp3 + T lymphocytes in OLK and OSCC samples by immunohistochemical (IHC) staining and analyzed their relation with clinical information and malignant transformation in OLK patients., Results: IHC staining demonstrated that the expression of PD-1 was significantly increased in the high-grade OLK group than in the low-grade OLK group, while PD-L1 was detected mainly in OSCC. The expression of CD3, CD8, and Foxp3 was found higher in the high-grade OLK group than in the low-grade OLK group, and the Foxp3 + cells were found more in the OSCC group than in the high-grade OLK group. PD-1 was significantly correlated with CD3 (p < 0.05, R = 0.52), CD8 (p < 0.05, R = 0.46), and Foxp3 (p < 0.05, R = 0.46), and the low PD-1-expression group showed a better malignant-free survival than high PD-1 expression group in the OLK (p < 0.05)., Conclusion: The PD-1/PD-L1 may induce immune suppression in OLK and accelerate the progress of malignant transformation., (© 2022 Wiley Periodicals LLC.)

Objectives: Clinical evidence has suggested that oral function is associated with cognitive, physical, and nutritional status of older people. A smaller volume of masseter, a crucial muscle for mastication, was associated with frailty. It has remained unknown if smaller masseter is associated with cognitive impairment. The current study investigated the association between masseter muscle volume, nutritional status, and cognitive status in older people., Materials and Methods: We recruited 19 patients with mild cognitive impairment (MCI), 15 patients with Alzheimer's disease (AD), and 28 sex and age-matched non-cognitive impairment (non-CI) older subjects. The number of missing teeth (NMT), masticatory performance (MP), maximal hand-grip force (MGF), and calf circumference (CC) were assessed. The masseter volume index (MVI) was calculated based on the masseter volume measured using magnetic resonance imaging., Results: The MVI was significantly lower in the AD group, compared to the MCI as well as the non-CI group. Multiple regression analyses revealed that the MVI was significantly associated with nutritional status (as indexed by CC) in the analysis of combination of NMT, MP, and the MVI. Moreover, the MVI was a significant predictor of CC only in patients with cognitive impairment (i.e., MCI+AD) but not in the non-CI group., Conclusions: Our findings suggested that in addition to the NMT and MP, masseter volume is a critical oral factor associated with cognitive impairment., Clinical Relevance: Reduction of MVI should be carefully monitored for patients with dementia and frailty, to whom a lower MVI may indicate worse nutrient intake., Competing Interests: Declaration of Conflicting Interest The authors report no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Degenerative joint disease (DJD) of the temporomandibular joint (TMJ) is an important type of temporomandibular disorders (TMDs) potentially leading to orofacial pain and jaw dysfunction. Magnetic resonance imaging (MRI) is important in TMD diagnosis; however, its diagnostic ability for DJD remains unknown., Objective: To explore the utility of MRI in diagnosing DJD according to the latest diagnostic criteria for TMD and detecting condylar bone abnormalities and their severity., Methods: Overall, 122 participants were examined using cone-beam computed tomography (CBCT) and MRI. The sensitivity, specificity and accuracy of MRI for detecting DJD and different types of TMJ condylar bone abnormalities were calculated (considering CBCT as gold standard); in addition, we tested MRI and CBCT's consistency in scoring five types of condylar bone abnormalities., Results: The sensitivity and specificity of MRI for DJD were 95.3% and 43.1%, respectively. The MRI sensitivities for condylar flattening, erosion, osteophytes, sclerosis and cysts were 98.6%, 96.2%, 79.4%, 50%, and 79.2% (specificity, 53.6%, 48.3%, 81.6%, 83.3%, and 88.2%, respectively), respectively. The consistency between MRI and CBCT in assessing the severity of condylar bone abnormalities was fair-to-moderate (kappa coefficient: 0.278-0.491). The inter-observer consistency for CBCT was good, whereas for MRI, it was relatively poor., Conclusion: MRI can detect DJD and condylar bone abnormalities. However, MRI could not efficiently detect the severity of condylar bone abnormalities., (© 2022 John Wiley & Sons Ltd.)

Objective: Tertiary lymphoid structures (TLSs) provide sites for antigen presentation and activation of lymphocytes, promoting their infiltration; thus, enhancing specific immune responses. The aim of this comparative cross-sectional study was to reveal the characteristics and influence of TLSs in oral lichen planus (OLP) and oral epithelial dysplasia (OED) with lichenoid features., Methods: Clinical information and samples of 51 OLP and 19 OED with lichenoid features were collected. Immunohistochemistry was performed, and the structures where CD20+ B cells and CD3+ T cells aggregated with peripheral lymph node addressin positive (PNAd+) vessels were defined as TLSs. The results and clinical information were analysed., Result: TLS were found in 44 (86.3%) patients with OLP and 19 (100%) patients with OED. The TLS score was higher in OED group (p = 0.023), accompanied by an increased number of PNAd+ vessels. The TLS was significantly correlated with PNAd+ vessels (p = 0.027), CD20+ B (p < 0.001) and CD208+ dendritic cells (p = 0.001). Foxp3+ Treg cells but not CD8+ T cells infiltrated more severely in OED (p = 0.003) and increased when TLS score was high (p = 0.002)., Conclusions: This study revealed the widespread development of TLSs in the OLP and OED. The presence of TLSs showed a close relationship with dysplasia and may increase malignant potency by over-inducing Treg cells., (© 2021 Wiley Periodicals LLC.)

Objective: When the lesions in the sellar region are large, they can involve both the inside and outside the sella, which brings challenges to the differential diagnosis of pituitary macroadenoma and lesions other than macroadenoma. Therefore, this study explored the diagnostic value of an ectopic posterior pituitary hyperintense signal (EPPHS) in pituitary macroadenoma and its possible causes., Methods: The clinical and imaging data of 131 patients with sellar tumors or tumor-like lesions involving both intrasellar and extrasellar regions in the Affiliated Hospital of Guizhou Medical University from February 2011 to December 2021 were analyzed retrospectively. The diagnostic value of EPPHS in pituitary macroadenoma was analyzed. The differences in clinical and imaging indexes between the EPPHS-positive group and the EPPHS-negative group were compared., Results: These 131 cases of sellar tumors or tumor-like lesions involving both intrasellar and extrasellar regions included 91 cases of pituitary macroadenoma and 40 cases of lesions other than macroadenoma. The receiver operator characteristic (ROC) curve analysis suggested that EPPHS had a diagnostic value in diagnosing pituitary macroadenoma [area under the curve (AUC) = 0.857, P = 0.0001]. Compared with the EPPHS negative group, the median prolactin level in the EPPHS positive group was significantly higher ( P < 0.05). Through ROC curve analysis, prolactin value was found to be of diagnostic value for EPPHS (AUC = 0.612, P = 0.0312)., Conclusion: In sellar tumors or tumor-like lesions involving both intrasellar and extrasellar regions, the appearance of EPPHS is helpful in the diagnosis of pituitary macroadenoma. The formation of EPPHS may be related to injuries to the pituitary stalk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Gu, Fan, Du, Yu, Liu and Liao.)

Objective: The goal of this paper is to investigate the use of Potentilla bifurca in the treatment of type 2 diabetes., Materials and Methods: We analyzed the improvement effect of 3T3-L1 adipocytes under insulin resistance (IR) with the compounds of Potentilla bifurca., Results: The Potentilla bifurca can significantly improve the glycolipid metabolism disorder in 3T3-L1 adipocytes (the effect of MC compounds is very significant). It can improve insulin resistance by enhancing the glucose uptake of 3T3-L1 adipocytes, decreasing IL-6 content, and regulating the content of p-Akt/Akt, IKKβ, and p-NF-κBp65/NF-κBp65 in the IRS/PI3K/Akt signaling pathway., Conclusions: Studies have shown that Potentilla bifurca has the ability to regulate glucolipid metabolism and can be used in the treatment of type 2 diabetes.

Background: Pathological albuminuria (PAU) (urinary albumin creatinine ratio [UACR] ≥30 mg/g) is an independent risk factor of cardiovascular disease. PAU is more prevalent in men than women. We aimed to compare the association of PAU and the early phase of subclinical atherosclerosis (SA) between sexes., Methods: 1228 subjects aged 50-90 years were stratified by sex and UACR (normal or PAU). SA was defined as mean carotid intima-media thickness ≥75th percentile of the cohort. Demographics and SA prevalence were compared between groups. Multivariate logistic regression was performed to assess the relationship between PAU and SA., Results: Both men and women with PAU had increased prevalence of hypertension, anti-hypertensive therapy, and metabolic syndrome than controls. Men with PAU were older and had greater waist circumference and total body fat percentage. Sex disparity was observed in associations between waist-to-height ratio, total body fat, and UACR. After adjusting for traditional risk factors, multivariate logistic regression disclosed that PAU was independently associated with SA in men (adjusted odds ratio 1.867, 95% CI 1.066-3.210) but not in women., Conclusion: The relationship of PAU and SA differed between sexes. This result may highlight the need for sex-specific risk management strategies to prevent atherosclerosis.

Objective: Abscopal effect of radiotherapy refers to a clinical phenomenon that is characterized by the eradication of distant metastatic tumors following localized irradiation. Reports on the abscopal effect following pure radiotherapy have been relatively rare., Case Report: Herein, we reported a 70-year-old male patient, who has been subjected to swelling and pain in the left neck. Computed tomography examination presented a metastatic lymph node of the left cervical and an intra-abdominal mass which was located in hepatogastric space, upward of the pancreatic head. Histopathology of the left cervical lymph node further ensured a poorly-moderately differentiated form of squamous cell carcinoma. But the primary origin was not defined. This patient received radiotherapy on the metastatic lymph nodes of the left cervical (dose: 60 Gray in 30 fractions) only. After treatment, the pain in the left neck dramatically improved and the swelling of the radiation exposure site diminished gradually. Computed tomography examination also confirmed that the abdominal mass was significantly reduced., Conclusions: The abscopal effect, in this case, may help us to get a better understanding of the impact of radiotherapy.

Gut bacterial nitroreductases play an important role in reduction of various nitroaromatic compounds to the corresponding N-nitroso compounds, hydroxylamines or aromatic amines, most of which are carcinogenic and mutagenic agents. Inhibition of gut nitroreductases has been recognized as an attractive approach for reducing mutagen metabolites in the colon, so as to prevent colon diseases. In this study, the inhibitory effects of 55 herbal medicines against Escherichia coli(E. coli) nitroreductase (EcNfsA) were examined. Compared with other herbal extracts, Syzygium aromaticum extract showed superior inhibitory potency toward EcNfsA mediated nitrofurazone reduction. Then, the inhibitory effects of 22 major constituents in Syzygium aromaticum against EcNfsA were evaluted. Compared with other tested natural compounds, ellagic acid, corilagin, betulinic acid, oleanic acid, ursolic acid, urolithin M5 and isorhamnetin were found with strong to moderate inhibitory effect against EcNfsA, with IC 50 values ranging from 0.67 to 28.98 mol·L -1 . Furthermore, the inhibition kinetic analysis and docking simulation demonstrated that ellagic acid and betulinic acid potently inhibited EcNfsA (K i < 2 μmol·L -1 ) in a competitively inhibitory manner, which created strong interactions with the catalytic triad of EcNfsA. In summary, our findings provide new scientific basis for explaining the anti-mutagenic activity of Syzygium aromaticum, where some newly identified EcNfsA inhibitors can be used for developing novel agents to reduce the toxicity induced by bacterial nitroreductase., (Copyright © 2022 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The pathogenesis of white spot syndrome virus (WSSV) is largely unclear. In this study, we found that actin nucleation and clathrin-mediated endocytosis were recruited for internalization of WSSV into crayfish hematopoietic tissue (Hpt) cells. This internalization was followed by intracellular transport of the invading virions via endocytic vesicles and endosomes. After envelope fusion within endosomes, the penetrated nucleocapsids were transported along microtubules toward the periphery of the nuclear pores. Furthermore, the nuclear transporter Cq Importin α1/β1, via binding of ARM repeat domain within Cq Importin α1 to the nuclear localization sequences (NLSs) of viral cargoes and binding of Cq Importin β1 to the nucleoporins Cq Nup35/62 with the action of Cq Ran for docking to nuclear pores, was hijacked for both targeting of the incoming nucleocapsids toward the nuclear pores and import of the expressed viral structural proteins containing NLS into the cell nucleus. Intriguingly, dysfunction of Cq Importin α1/β1 resulted in significant accumulation of incoming nucleocapsids on the periphery of the Hpt cell nucleus, leading to substantially decreased introduction of the viral genome into the nucleus and remarkably reduced nuclear import of expressed viral structural proteins with NLS; both of these effects were accompanied by significantly inhibited viral propagation. Accordingly, the survival rate of crayfish post-WSSV challenge was significantly increased after dysfunction of Cq Importin α1/β1, also showing significantly reduced viral propagation, and was induced either by gene silencing or by pharmacological blockade via dietary administration of ivermectin per os . Collectively, our findings improve our understanding of WSSV pathogenesis and support future antiviral designing against WSSV. IMPORTANCE As one of the largest animal DNA viruses, white spot syndrome virus (WSSV) has been causing severe economical loss in aquaculture due to the limited knowledge on WSSV pathogenesis for an antiviral strategy. We demonstrate that the actin cytoskeleton, endocytic vesicles, endosomes, and microtubules are hijacked for WSSV invasion; importantly, the nuclear transporter Cq Importin α1/β1 together with Cq Ran were recruited, via binding of Cq Importin β1 to the nucleoporins Cq Nup35/62, for both the nuclear pore targeting of the incoming nucleocapsids and the nuclear import of expressed viral structural proteins containing the nuclear localization sequences (NLSs). This is the first report that NLSs from both viral structure proteins and host factor are elaborately recruited together to facilitate WSSV infection. Our findings provide a novel explanation for WSSV pathogenesis involving systemic hijacking of host factors, which can be used for antiviral targeting against WSSV disease, such as the blockade of Cq Importin α1/β1 with ivermectin.

Background: Sarcopenia, defined as age-related diminution of muscle mass and strength, is a key determinant of frailty status and progression. We investigated the hypothesis that changing masseter muscle structure with advancing age may contribute to the development of frailty., Methods: Study data were excerpted from the I-Lan Longitudinal Aging Study, a research cohort of community-dwelling residents aged ≥53 years from Yilan (I-Lan) County, Taiwan. The study sample comprised 56 subjects classified as frail, 41 pre-frail, and 41 robust, according to Cardiovascular Health Study criteria; all groups were matched by age and sex. Masseter muscle volume was quantified based on T1-weighted magnetic resonance imaging, and adjusted for height to derive the masseter volume index (MVI). Appendicular skeletal muscle mass index (SMI) was determined by dual-energy X-ray absorptiometry, and used to derive the height-adjusted skeletal mass index (SMI). Nutrition status was assessed with the Mini-Nutritional Assessment (MNA) form., Results: The MVI was significantly smaller in frail versus pre-frail subjects. Among frail individuals, only the MVI was significantly correlated with MNA scores. MVI, but not SMI, was associated with increased risk of being frail versus pre-frail. An MVI cut-off score of 9.5 cm 3 /m 2 in males discriminated frail from pre-frail status with acceptable sensitivity and specificity. Low MVI was associated with the frailty criteria of slowness., Conclusions: MVI is a potential clinical index for evaluating phenotypic frailty. Diminished masseter muscle volume may predispose pre-frail/frail elders to depletion of physical reserves, consequent to its detrimental effect on oral functioning and nutrient intake., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: This study aimed to analyze the current research status and trends of publications on relapsed/refractory Non-Hodgkin lymphoma (r/r NHL) using CiteSpace software and to know which centers and authors we should follow in the first place while doing research on r/r NHL., Materials and Methods: The publications were retrieved from the Web of Science Core collection database, and CiteSpace (5.5.R5) software was used to analyze the authors, institutions, countries, and keywords., Results: A total of 567 publications from 2009 to 2021 were retrieved, and the most fertile authors, institutions, nationalities and keywords in the field of r/r NHL were identified. Pier Luigi Zinzani team, Kensei Tobinai team, Andre Goy team, and Julie M. Vose team are recognized the main research teams in this field. USA makes the greatest contribution having research funds for r/r NHL. Key cluster areas of research include mantle cell lymphoma, pathway, lymphoma, relapse, pixantrone, Non-Hodgkin lymphoma, romidepsin, relapsed, T-cell lymphoma, and activated T cells. According to the keywords' timeline, the research trends of r/r NHL changed from bone marrow transplantation, radioimmunotherapy, chemotherapy to novel target drugs (like ibritumomab tiuxetan, inhibitor) and criteria EBM., Conclusions: The bibliometric study provides insights into hotspots and trends in the field of r/r NHL in the past 12 years. It serves us to extract useful information from complex data and provide information for clinicians and researchers.

Background: The effectiveness of platelet-rich plasma (PRP) injection combined with physical therapy for the treatment of temporomandibular joint osteoarthritis (TMJ-OA) has not been studied., Objectives: To assess the effectiveness of PRP injection combined with individualised comprehensive physical therapy for the treatment of TMJ-OA., Methods: This prospective cohort study included 40 patients with TMJ-OA who received PRP injection or PRP injection combined with individualised comprehensive physical therapy. Pain intensity, maximum mouth opening, temporomandibular joint sounds, and the Jaw Functional Limitation Scale (JFLS) scores and imaging findings were compared before treatment and during follow-up., Results: The pain intensity, maximum mouth opening, and temporomandibular joint sounds of the two groups significantly improved with an increase in treatment time (p < .05). The pain improvement in the combined treatment group was greater than that in the PRP injection group at 3 and 6 months (p < .05). The improvement of mouth opening was better in the combined treatment group, whereas the improvement of joint sounds was better in the PRP injection group. The improvement in JFLS scores in the combined treatment group was greater than that in the PRP injection group at 6 months (p < .05). The imaging improvement rates of the two groups were similar., Conclusions: Platelet-rich plasma injection can significantly improve pain, mouth opening, abnormal joint sound, and mandibular function in patients with TMJ-OA and has good repair effect on condylar bone defects. PRP injection combined with individualised comprehensive physical therapy can effectively control the medium- and long-term pain of patients., (© 2021 John Wiley & Sons Ltd.)

Introduction: Colorectal cancer has been ranked third among the most common cancers worldwide and raised to the second leading cause of cancer death with nearly one-tenth of cancer-related deaths globally, and nearly half of colorectal cancer patients present with or develop colorectal cancer liver metastasis (CRLM). Buzhong Tiaogan Formula (BTF) has been proven to treat CRLM in our team, but there are lacking of evidence on its effective in delaying colorectal liver metastasis (liver depression spleen deficiency type), so we will evaluate the efficacy and safety of BTF in preventing the occurrence of CRLM., Methods: This randomized controlled trial (RCT) will be carried out in 3 different hospitals in Shanxi Province planning to recruit 150 CRLM patients with the type of liver depression spleen deficiency. The control group will be treated by basic antitumor therapy and the treatment group will use BTF plus basic antitumor therapy. The primary outcomes will be quality of life of included patients, the time of occurrence of liver metastasis, the score of traditional Chinese medicine symptom for the type of liver depression spleen deficiency; and the secondary outcomes will include overall survival, progression-free survival, DFS, tumor microenvironment and immune state of the included patient. Safety evaluation will be recorded during the whole study. All data in this RCT will be analyzed by SPSS 23.0 software. This study has been approved by the Clinical Research Ethics Committee of Shanxi Province Hospital of Traditional Chinese medicine (2021Y-06016)., Discussion: The results of this RCT will contribute to BTF for delaying colorectal liver metastasis (liver depression spleen deficient type). And the results from this RCT will be published in a relevant journal after finished., Trial Registration: ChiMCTR2100005268 (September 4, 2021)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, have prominent roles in the development of solid tumors as stromal targets. However, the underlying mechanism of CAFs' function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we investigated the role of lysyl oxidase (LOX) expression in CAFs in tumor stromal remodeling and the mechanism of its effect on OSCC progression., Methods: Multiple immunohistochemistry (IHC) staining was performed to detect the correlation of CAFs and LOX in the stroma of OSCC specimens, as well as the correlation with clinicopathological parameters and prognosis. The expression of LOX in CAFs were detected by RT-qPCR and western blot. The effects of LOX in CAFs on the biological characteristics of OSCC cell line were investigated using CCK-8, wound-healing and transwell assay. CAFs were co-cultured with type I collagen in vitro, and collagen contraction test, microstructure observation and rheometer were used to detect the effect of CAFs on remodeling collagen matrix. Then, collagen with different stiffness were established to investigate the effect of matrix stiffness on the progression of OSCC. Moreover, we used focal adhesion kinase (FAK) phosphorylation inhibitors to explored whether the increase in matrix stiffness promote the progression of OSCC through activating FAK phosphorylation pathway., Results: LOX was colocalized with CAFs in the stroma of OSCC tissues, and its expression was significantly related to the degree of malignant differentiation and poor prognosis in OSCC. LOX was highly expressed in CAFs, and its knockdown impaired the proliferation, migration, invasion and EMT process of OSCC cells. The expression of LOX in CAFs can catalyze collagen crosslinking and increase matrix stiffness. Furthermore, CAFs-derived LOX-mediated increase in collagen stiffness induced morphological changes and promoted invasion and EMT process in OSCC cells by activating FAK phosphorylation pathway., Conclusions: Our findings suggest that CAFs highly express LOX in the stroma of OSCC and can remodel the matrix collagen microenvironment, and the increase in matrix stiffness mediated by CAFs-derived LOX promotes OSCC development through FAK phosphorylation pathway. Thus, LOX may be a potential target for the early diagnosis and therapeutic treatment of OSCC., (© 2021. The Author(s).)

Autophagy is an evolutionarily conserved process of degradation in eukaryotes, which can form double-membrane vesicles for delivering the trapped cargo to lysosome for degradation, also facilitate host cells against the invasion of foreign pathogens. Recently, autophagy was reported to participate in viral infection in crustaceans. White spot syndrome virus (WSSV) is the most severely viral pathogen for farmed crustaceans, particularly in crayfish and shrimp. In this review, we summarized and discussed the current findings of autophagy involved in WSSV infection in crustaceans, particularly focusing on the identified autophagy-related molecules and their effects on viral infection. We hope this summary will provide us a better understanding of autophagy and its contribution to antiviral immunity in crustaceans., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Introduction: CRC, the incidence of the fourth highest among males and the third among females, is one of the malignant tumors that seriously threaten human health. The principle of treatment for advanced stage CRC is a multidisciplinary and comprehensive treatment based on chemotherapy, which always bring significant toxic side effects. CHM has advantages in the treatment of tumors with the effect on improving clinical symptoms and reducing side effects. GGQL formula is mainly used for treating abnormal defecates caused by damp-heat, so we will evaluate the clinical efficacy and safety of modified GGQL formula for patients with advanced CRC with the type of damp-heat in this study., Methods: Multicenter RCT with two parallel groups in three hospitals planning to recruit 120 CRC patients with the type of damp-heat will be conducted. The control group will be treated by basic antitumor therapy and the treatment group will use modified GGQL formula plus basic antitumor therapy. The primary outcomes will be quality of life, TCM symptom score, PFS and OS, and the secondary outcomes will be performance status, size of tumor, tumor marker in the serum, tumor microenvironment and immune status. All analyses will be based on an intention-to-treat principle. This study was approved by the Human Research Ethics Committee of Shanxi Province Hospital of Traditional Chinese medicine (2021Y-06017). The results will be published in relevant journal., Discussion: The results of this RCT will contribute to Chinese herbal medicine for treating CRC patients with the type of damp heat accumulation., Trial Registration: ChiCTR2100050754 (September 4, 2021)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Insulin resistance (IR) is a known risk factor for cardiovascular disease (CVD) in non-diabetic patients through the association of hyperglycemia or associated metabolic factors. The triglyceride glucose (TyG) index, which was defined by incorporating serum glucose and insulin concentrations, was developed as a surrogate marker of insulin resistance. We aimed to investigate the association between the TyG index and the early phase of subclinical atherosclerosis (SA) between the sexes., Methods: The I-Lan Longitudinal Aging Study (ILAS) enrolled 1457 subjects aged 50-80 years. For each subject, demographic data and the TyG index {ln[fasting triglyceride (mg/dL)  ×  fasting plasma glucose (mg/dL)]/ 2 } were obtained. Patients were further stratified according to sex and the 50th percentile of the TyG index (≥  8.55 or  <  8.55). SA was defined as the mean carotid intima-media thickness (cIMT) at the 75th percentile of the entire cohort. Demographic characteristics and the presence of SA were compared between the groups. Logistic regression analysis was performed to assess the relationship between TyG index and SA., Results: Patients with a higher TyG index (≥  8.55) had a higher body mass index (BMI), hypertension (HTN) and diabetes mellitus (DM). They had higher lipid profiles, including total cholesterol (T-Chol) and low-density lipoprotein (LDL), compared to those with a lower TyG index (<  8.55). Gender disparity was observed in non-diabetic women who had a significantly higher prevalence of SA in the high TyG index group than in the low TyG index group. In multivariate logistic regression analysis, a high TyG index was independently associated with SA in non-diabetic women after adjusting for traditional risk factors [adjusted odds ratio (OR): 1.510, 95% CI 1.010-2.257, p  =  0.045] but not in non-diabetic men. The TyG index was not associated with the presence of SA in diabetic patients, irrespective of sex., Conclusion: A high TyG index was significantly associated with SA and gender disparity in non-diabetic patients. This result may highlight the need for a sex-specific risk management strategy to prevent atherosclerosis., (© 2021. The Author(s).)

Activin A, a cytokine belonging to the transforming growth factor-β family, has been shown to play pivotal roles in tissue remodeling after renal injury and is present in elevated levels in diabetic patients. However, the association between activin A and albuminuria remains unclear. We aimed to evaluate their association by using cross-sectional data from community-dwelling middle-aged and older adults in Taiwan. We assessed 466 participants (67% male; mean age 71 ± 13 years) from the I-Lan Longitudinal Aging study for whom data pertaining to serum activin A level and urine albumin-to-creatinine ratio (UACR) were available. Of these, 323 (69%) had normal albuminuria, 123 (26%) had microalbuminuria, and 20 (4%) had overt albuminuria. Patients with overt albuminuria and microalbuminuria had significantly higher activin A concentrations than those in the normal albuminuria group (p < 0.001). Circulating activin A was significantly correlated with multiple risk factors, including higher systolic blood pressure and higher UACR. Univariate and multivariate results indicated that activin A level was an independent variable for albuminuria. The cutoff value of 602 pg/mL of activin A demonstrated a sensitivity of 70.6% and specificity of 75.7% (AUC 0.774) in diagnosing overt albuminuria. In conclusion, middle-aged and older adults with elevated activin A levels were associated with a higher incidence of albuminuria., (© 2021. The Author(s).)

White spot syndrome virus (WSSV) is currently the most severely viral pathogen for farmed crustaceans such as shrimp and crayfish, which has been causing huge economic losses for crustaceans farming worldwide every year. Unfortunately, study on the molecular mechanisms of WSSV has been restricted by the lack of crustacean cell lines for WSSV propagation as well as the incompletely annotated genomes for host species, resulting in limited elucidation for WSSV pathogenesis at present. In addition to the findings of anti-WSSV response in shrimp, some of novel cellular events involved in WSSV infection have been recently revealed in crayfish, including endocytosis and intracellular transport of WSSV, innate immune pathways in response to WSSV infection, and regulation of viral gene expression by host genes. Despite these advances, many fundamental gaps in WSSV pathogenesis are still remaining, for example, how WSSV genome enters into nucleus and how the progeny virions are fully assembled in the host cell nucleus. In this review, recent findings in WSSV infection mechanism and the antiviral immunity against WSSV in crayfish are summarized and discussed, which may provide us a better understanding of the WSSV pathogenesis as well as new ideas for the target design of antiviral drugs against WSSV in crustaceans farming., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Protein phosphatase 2A (PP2A) is an important serine/threonine phosphatase, a highly conserved enzyme widely expressed in eukaryotic cells, which accounts for a majority of the serine/threonine phosphatase activity in cells implicated in regulation of immune signaling pathways and antiviral response. However, most of studies about PP2A have been conducted in mammals but few in crustaceans. In this study, two subunits of PP2A (named as CqPP2Ab and CqPP2Ac) were characterized to be involved in white spot syndrome virus (WSSV) infection in the haematopoietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus. The open reading frame (ORF) of CqPP2Ab was 1341 bp encoding 446 amino acids with seven WD40 domains, and the ORF of CqPP2Ac was 930 bp encoding 309 amino acids with a PP2Ac domain. Tissue distribution analysis showed that the mRNA transcript of CqPP2Ab and CqPP2Ac were both widely expressed in all the tested tissues with the highest expression in hemocyte, followed by high expression in Hpt. The gene expressions of CqPP2Ab and CqPP2Ac were both significantly down-regulated at 6 h post WSSV infection (6 hpi) in Hpt cells. Importantly, the expression of viral immediate early gene IE1 and late viral gene envelope protein VP28 were both significantly increased post WSSV infection after gene silencing of CqPP2Ab or CqPP2Ac in Hpt cells, suggesting that CqPP2Ab and CqPP2Ac could inhibit WSSV infection in Hpt cells, probably by increasing the antimicrobial substances expression in consideration to the significantly reduced expression of anti-lipopolysaccharide factor, crustin, and lysozyme after gene silencing of CqPP2Ab or CqPP2Ac, respectively. These findings provide a new light on the mechanism of WSSV infection and the antiviral response in crustaceans., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Gastrodiae Rhizoma-Uncariae Ramulus cum Uncis is the most frequently used herbal pair in the treatment of Parkinson's disease(PD). Gastrodin and isorhynchophylline are important components of Gastrodiae Rhizoma-Uncariae Ramulus cum Uncis herb pair with anti-Parkinson mechanism. This study aimed to investigate the effect of gastrodin combined with isorhynchophylline on 1-methyl-4-phenylpyridinium(MPP~+)-induced apoptosis of PC12 cells and their antioxidant mechanism. The leakage of lactate dehydrogenase(LDH) from cells to media was analyzed by spectrophotometry. Apoptotic cells were labeled with Annexin V-fluorescein isothiocyanate(FITC) and propidium iodide(PI) and analyzed by flow cytometry. The cell cycle was analyzed using propidium iodide(PI) staining. Lipid peroxidation(LPO) level was analyzed by spectrophotometry. The mRNA expression of caspase-3 was examined by Real-time RT-PCR. The protein expressions of heme oxygenase 1(HO-1) and NADPH: quinoneoxidore-ductase 1(NQO-1) were determined by Western blot. Gastrodin combined with isorhynchophylline reduced the percentage of Annexin V-positive cells and cell cycle arrest in MPP~+-induced PC12 cells. Gastrodin combined with isorhynchophylline down-regulated the mRNA expression of caspase-3, up-regulated the protein expressions of HO-1 and NQO-1, and reduced LPO content in MPP~+-induced PC12 cells. PD98059, LY294002 or LiCl could partially reverse these changes pretreated with gastrodin combined with isorhynchophylline, suggesting that gastrodin combined with isorhynchophylline inhibited MPP~+-induced apoptosis of PC12 cells and oxidative stress through ERK1/2 and PI3 K/GSK-3β signal pathways. Our experiments showed that gastrodin combined with isorhynchophylline could down-re-gulate the mRNA expression of caspase-3 and up-regulate the protein expressions of HO-1 and NQO-1, so as to reduce oxidative stress and inhibit apoptosis.

Both physical and cognitive deficits occur in the aging process. We operationally defined the phenomenon as physio-cognitive decline syndrome (PCDS) and aimed to decipher its corresponding neuroanatomy patterns and neurocircuit. High resolution 3T brain magnetic resonance imaging (MRI) images from a community-dwelling longitudinal aging cohort were analysed. PCDS was defined as weakness (handgrip strength) and/or slowness (gait speed) concomitant with impairment in any cognitive domain (defined by 1.5 standard deviation below age, sex-matched norms), but without dementia or disability. Among 1196 eligible ≥ 50-year-old (62±9 years, 47.6%men) subjects, 15.9% had PCDS. Compared to the other participants, individuals with PCDS had significantly lower gray-matter volume (GMV) in the bilateral amygdala and thalamus, right hippocampus, right temporo-occipital cortex, and left cerebellum VI and V regions. The regions of reduced GMV in people with PCDS were similar between the middle-aged and older adults; whereas larger clusters with more extensive GMV-depleted regions were observed in ≥65-year-olds with PCDS. Diffusion-weighted tractography showed disrupted hippocampus-amygdala-cerebellum connections in subjects with PCDS. The neuroanatomic characteristics revealed by this study provide evidence for pathophysiological processes associated with concomitant physio-cognitive decline in the elderly. This neurocircuit might constitute a target for future preventive interventions.

As the most severely lethal viral pathogen for crustaceans in both brackish water and freshwater, white spot syndrome virus (WSSV) has a mechanism of infection that remains largely unknown, which profoundly limits the control of WSSV disease. By using a hematopoietic tissue (Hpt) stem cell culture from the red claw crayfish Cherax quadricarinatus suitable for WSSV propagation in vitro , the intracellular trafficking of live WSSV, in which the acidic-pH-dependent endosomal environment was a prerequisite for WSSV fusion, was determined for the first time via live-cell imaging. When the acidic pH within the endosome was alkalized by chemicals, the intracellular WSSV virions were detained in dysfunctional endosomes, resulting in appreciable blocking of the viral infection. Furthermore, disrupted valosin-containing protein ( C. quadricarinatus VCP [ Cq VCP]) activity resulted in considerable aggregation of endocytic WSSV virions in the disordered endosomes, which subsequently recruited autophagosomes, likely by binding to Cq GABARAP via Cq VCP, to eliminate the aggregated virions within the dysfunctional endosomes. Importantly, both autophagic sorting and the degradation of intracellular WSSV virions were clearly enhanced in Hpt cells with increased autophagic activity, demonstrating that autophagy played a defensive role against WSSV infection. Intriguingly, most of the endocytic WSSV virions were directed to the endosomal delivery system facilitated by Cq VCP activity so that they avoided autophagy degradation and successfully delivered the viral genome into Hpt cell nuclei, which was followed by the propagation of progeny virions. These findings will benefit anti-WSSV target design against the most severe viral disease currently affecting farmed crustaceans. IMPORTANCE White spot disease is currently the most devastating viral disease in farmed crustaceans, such as shrimp and crayfish, and has resulted in a severe ecological problem for both brackish water and freshwater aquaculture areas worldwide. Efficient antiviral control of WSSV disease is still lacking due to our limited knowledge of its pathogenesis. Importantly, research on the WSSV infection mechanism is also quite meaningful for the elucidation of viral pathogenesis and virus-host coevolution, as WSSV is one of the largest animal viruses, in terms of genome size, that infects only crustaceans. Here, we found that most of the endocytic WSSV virions were directed to the endosomal delivery system, strongly facilitated by Cq VCP, so that they avoided autophagic degradation and successfully delivered the viral genome into the Hpt cell nucleus for propagation. Our data point to a virus-sorting model that might also explain the escape of other enveloped DNA viruses., (Copyright © 2020 American Society for Microbiology.)

The current evidence regarding the association between vitamin D deficiency and cardiovascular diseases/metabolic disorders is contradictory and inconclusive. In this large-scale observational study, we investigated the relationship between the serum 25-hydroxy vitamin D3 [25(OH)D] concentration and subclinical atherosclerosis in an elderly Asian population. In the I-Lan longitudinal study (ILAS), 1798 elderly, aged 50 and older, were enrolled. For each subject, serum 25-hydroxy vitamin D3 [25(OH)D] concentration and demographic data were recorded. The participants were divided into two groups according to their serum 25(OH)D level (sufficient, > 20 ng/mL and deficient, ≤ 20 ng/mL). Carotid intima-media thickness (cIMT) was measured at bilateral common carotid arteries. Subclinical atherosclerosis was defined as a mean cIMT > 0.81 mm. The mean subject age was 64 ± 9 years old, and 604 (33.6%) were identified as having serum 25(OH)D level ≤ 20 ng/mL. Subjects with serum 25(OH)D level ≤ 20 ng/mL were younger, more likely to be female and smoker, and had a higher incidence of hypertension, dyslipidemia, and metabolic syndrome, compared to those with serum 25(OH)D level > 20 ng/mL. Additionally, patients with serum 25(OH)D level ≤ 20 ng/mL were associated with a lower risk of subclinical atherosclerosis (crude OR: 0.63, 95% CI 0.50-0.81, p < 0.001), according to univariate analysis. However, after adjusting for gender and age, serum 25(OH)D level ≤ 20 ng/mL was not a significant risk factor for subclinical atherosclerosis. Serum 25(OH)D level ≤ 20 ng/mL was not an independent risk factor for subclinical atherosclerosis in this large elderly Asian population. Association observed in the univariate analysis may be confounded by gender or comorbidities.

Mounting lines of evidence indicated that the "colony stimulating factor-1 (CSF-1)/tumor-associated macrophage (TAM)" signature plays an important role in the progression, invasion and metastasis of multiple tumors. However, the potential role of CSF-1/TAM in oral squamous cell carcinoma (OSCC) remains largely unknown. In the present study, the expression of CSF-1 from 99 OSCC specimens and its correlation with clinicopathological features and patient outcomes were investigated. Meanwhile, the correlation between CSF-1 expression and TAM infiltration was also explored. To investigate the potential effect of CSF-1 on tumor growth, nude mice were subcutaneously injected with Cal27 cell line and a small molecule inhibitor of CSF-1 (BZL945). The results showed that the high expression rate of CSF-1 (52%) was found in OSCC, and the upregulation of CSF-1 was closely correlated with lymph node metastasis and clinical stage. Additionally, there was a positive correlation between a high CSF-1 level and elevated TAM infiltration. The xenograft model study showed that CSF-1 signal blockade inhibited tumor growth, with a significant synchronous decrease in CSF-1 expression and TAM infiltration. Overall, our findings indicated that CSF-1 plays a crucial role in TAMs-mediated OSCC tumor progression and invasion. The "CSF-1/TAM" signaling axis may serve as a prospective target for anti-tumor therapy of OSCC., Competing Interests: None., (AJTR Copyright © 2020.)

Objective: To evaluate the impact of individual components of unfavorable body composition and their combinations on quality of life (QoL) among middle-aged and older adults., Methods: Data from 1779 participants (53.1 % female; mean age 63.9 ± 9.2 years) from the I-Lan Longitudinal Aging Study were analyzed in this study. Demographic characteristics of all participants and data from anthropometric measurements, functional assessments, dual-energy X-ray absorptiometry scans, and surveys of QoL were obtained. Low skeletal muscle mass was defined by the Asian Working Group of Sarcopenia consensus, and obesity was defined by waist circumference (WC), body fat percentage, or body mass index (BMI). QoL was assessed by the 12-Item Short Form Health Survey version 2, which was divided into the physical component summary (PCS) and mental component summary (MCS). The composite score was determined based on the items of unfavorable body composition. Independent associations between unfavorable body composition components and QoL were evaluated by the multivariate linear regression model. Z transformation was performed to facilitate evaluation between different components of body composition and their relationship with QoL., Results: All definitions of obesity were significantly associated with a lower PCS score (WC: β=-1.2, SE = 0.3, p < 0.001; body fat percentage: β=-1.0, SE = 0.3, p < 0.001; BMI: β=-0.9, SE = 0.3, p = 0.002 in the fully adjusted model). The PCS score decreased linearly as the composite score of unfavorable body composition increased, especially when obesity was defined by WC (score = 1: β=-0.7, SE = 0.4, p = 0.053, score = 2: β=-1.1, SE = 0.4, p = 0.008; score = 3: β=-2.4, SE = 1.0, p = 0.013). After Z transformation, obesity was significantly negatively associated with the PCS score (β=-0.9∼-0.2, SE = 0.1∼0.2, p values all less than 0.01). In contrast, a one-standard-deviation increase in WC was associated with a significantly higher MCS score (β = 0.3, SE = 0.1, p = 0.019)., Conclusions: Community-dwelling middle-aged and older people with obesity had significantly lower PCS scores, and the effect was enhanced when low skeletal muscle mass or osteopenia/osteoporosis was present. Central obesity was the only unfavorable body composition parameter with negative effects on both the physical and the mental domains of QoL. Further longitudinal or intervention studies are needed to evaluate the impact on QoL of changes in body composition that occur with aging., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway is pivotal in immune responses for a variety of pathogens in both vertebrates and invertebrates. Domeless (Dome), as a unique cytokine receptor, involves in the upstream JAK/STAT pathway in invertebrates. In this study, the full-length cDNA sequence of a cytokine receptor Dome was identified from red claw crayfish Cherax quadricarinatus (named as CqDome), which contained an open reading frame of 4251 bp, encoding 1416 amino acids. The CqDome contained extracellular conservative domains of a signal peptide, two cytokine binding modules (CBM), three fibronectin-type-III-like (FN3) domains and a transmembrane region. Tissue distribution analysis showed that CqDome generally expressed in all the tissues selected with a high expression in hemocyte. The gene expression of both the viral immediately early gene (IE1) and a late gene envelope protein VP28 of white spot syndrome virus (WSSV) were significantly decreased after gene silencing of CqDome in crayfish haematopoietic tissue (Hpt) cells, indicating a key role of CqDome in promoting WSSV infection. Furthermore, the phosphorylation level of CqSTAT was significantly inhibited by gene silencing of CqDome in Hpt cells, indicating that CqDome participated in signal transduction of JAK/STAT pathway in red claw crayfish. These data together suggest that CqDome is likely to promote WSSV infection via JAK/STAT pathway, which sheds new light on further elucidation of the pathogenesis of WSSV., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Barrier-to-autointegration factor (BAF) is a highly conserved DNA binding protein that participates in a variety of biological processes such as transcription, epigenetic regulation and antiviral immunity in vertebrates. However, the function of BAF is poorly understood in crustaceans. In this study, we identified a barrier-to-autointegration factor (CqBAF) from red claw crayfish Cherax quadricarinatus, which was responsive to white spot syndrome virus (WSSV) infection. The full-length cDNA sequence of CqBAF was 544 bp, including an open reading frame of 273 bp encoding 90 amino acids, a 107 bp of 5'-Untranslated Regions (5'-UTR) and a 164 bp of 3'-UTR. Gene expression analysis showed that CqBAF was distributed in all tissues examined with the highest expression in the crayfish haematopietic tissue (Hpt), which protein expression was also significantly up-regulated by WSSV infection in Hpt cells. Furthermore, the transcripts of both an immediate early gene IE1 and a late envelope protein gene VP28 of WSSV were clearly reduced in Hpt cells after gene silencing of CqBAF. Importantly, the promoter activity of two immediate early genes of WSSV, including WSV051 and IE1, was strongly enhanced by the increased phosphorylation of CqBAF, which also facilitated the accumulation of CqBAF protein in the cytoplasm of Sf9 cells. Taken together, these data suggest that CqBAF is likely to increase the replication of WSSV by promoting the transcription of viral immediate early genes, probably regulated by phosphorylation of CqBAF, which sheds new light on the molecular mechanism of WSSV infection., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The aging process is accompanied by changes in the brain's cortex at many levels. There is growing interest in summarizing these complex brain-aging profiles into a single, quantitative index that could serve as a biomarker both for characterizing individual brain health and for identifying neurodegenerative and neuropsychiatric diseases. Using a large-scale structural covariance network (SCN)-based framework with machine learning algorithms, we demonstrate this framework's ability to predict individual brain age in a large sample of middle-to-late age adults, and highlight its clinical specificity for several disease populations from a network perspective. A proposed estimator with 40 SCNs could predict individual brain age, balancing between model complexity and prediction accuracy. Notably, we found that the most significant SCN for predicting brain age included the caudate nucleus, putamen, hippocampus, amygdala, and cerebellar regions. Furthermore, our data indicate a larger brain age disparity in patients with schizophrenia and Alzheimer's disease than in healthy controls, while this metric did not differ significantly in patients with major depressive disorder. These findings provide empirical evidence supporting the estimation of brain age from a brain network perspective, and demonstrate the clinical feasibility of evaluating neurological diseases hypothesized to be associated with accelerated brain aging., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Invertebrates rely solely on the innate immune system to protect against virus infection, while the viral infection must rely on the transcriptional system of the host cell to achieve the expression of viral genes, which is naturally regulated by the host's transcriptional system. However, the mechanism of the host against viral transcription in host cells is still poorly understood in crustaceans. Previously, we found that the partial transcript sequence of a negative elongation factor E (named as CqNELF-E) was up-regulated in a differentially expressed transcriptome library of the haematopietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus upon white spot syndrome virus (WSSV) infection, suggesting a possible role of CqNELF-E in WSSV-host interaction. In the present study, we revealed the function of CqNELF-E. The full-length cDNA sequence of CqNELF-E was identified with 1726 bp from red claw crayfish, which contained an open reading frame of 816 bp, encoding 271 amino acids. Amino acid sequencing analysis revealed that the CqNELF-E had a conserved RNA recognition motif (RRM) and a leucine zipper motif (LZM). Tissue distribution analysis showed that CqNELF-E was widely expressed in various tissues with the highest expression in muscle, relatively abundant in Hpt and the lowest presence in heart. Interestingly, the gene expression of CqNELF-E was significantly up-regulated at both 6 and 12 hpi after WSSV infection in Hpt cell cultures in red claw crayfish. In addition, the expression of both the viral immediately early gene (IE) 1 (IE1) and a late gene envelope protein VP28 were significantly increased after gene silencing of CqNELF-E in Hpt cells, indicating the potential suppression role of CqNELF-E against the viral infection. Further study revealed that the CqNELF-E had an inhibitory effect on the promoter activity of WSSV IE genes WSV051, WSV069 (IE1) and WSV083 by a dual luciferase reporter gene assay. Taken together, these results suggest that CqNELF-E plays an antiviral role, probably via inhibition on the viral transcription activity in WSSV infection in a crustacean., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In contrast to that hypoacetylation of histones is associated with condensed chromatin and gene silencing, the hyperacetylation of histones can promote an "open chromatin" conformation and transcriptional activation, which is recruited by some viruses to enhance the viral genome replication in host cells. However, the function of histone acetylation modification in the infection of white spot syndrome virus (WSSV), one of the most virulent pathogens for crustaceans like shrimp and crayfish at present, is still unknown. Previously, we found that the transcript of a histone K-Lysine acetyltransferase CqKAT2A-like gene was down-regulated in a differentially expressed transcriptome library of the haematopietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus upon WSSV infection at 12 hpi. To further reveal its possible role in anti-WSSV response, CqKAT2A-like gene was then identified with an open reading frame (ORF) of 2523 bp encoding 840 amino acids, which contained a conserved PCAF-N domain, acetyltransf1 domain and bromo domain. Gene expression analysis showed that CqKAT2A-like was distributed in all tissues examined with high presence in haemocyte and muscle, and the transcript was significantly down-regulated after WSSV infection in Hpt cells. Furthermore, the level of histone H3 acetylation (H3ac) was strongly reduced by gene silencing of CqKAT2A-like, which was accompanied with the significantly decreased gene expression of WSSV in Hpt cells, suggesting that CqKAT2A-like gene can promote the activity H3ac and the replication of WSSV. When the H3ac was induced by histone deacetyltransferase inhibitor TSA, the transcription of WSSV genes including both IE1 and VP28 genes was significantly increased, indicating that H3ac participated in WSSV infection in Hpt cells. Taken together, these data suggest that CqKAT2A-like gene might promote the replication of WSSV by regulating H3ac, which sheds new light on the pathogenesis of WSSV in crustaceans., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: This study aimed to assess the clinical significance of the maximal first derivative of the radial pulse wave (Rad dP/dtmax) in monitoring cardiac function with different perioperative patients by researching the relationship between Rad dP/dtmax and cardiac output (CO)., Methods: Patients with non-pump coronary artery bypass grafting (CABG) and open liver tumor resection (OLTR) were enrolled in this study (n=10). CO was measured using the thermodilution Swan-Ganz catheter method and Rad dP/dtmax was acquired by the analysis of patients' left radial artery pressure waveform through the PowerLab data acquisition device. CO, Rad dP/dtmax, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary artery wedge pressure (PAW), and body surface area was recorded. Data were analyzed using a mixed linear model of time-dependent covariates to duplicate the data., Results: The bivariate correlation coefficients of Rad dP/dtmax and CO were 0.526 and 0.413. The result of the multivariate mixed linear model analysis showed that compared with other indicators, Rad dP/dtmax had the greatest standardized coefficient with CO in CABG patients. While in OLTR patients, HR, SBP, PAW, and DBP had larger standardized coefficients., Conclusions: Rad dP/dtmax could be a useful indicator to reflect and predict the acute changes in cardiac function in perioperative patients, especially for patients with cardiac dysfunction or contractility abnormality., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-19-3161). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Food supplements can modulate the composition of human intestinal microflora due to the potential capacity of improving the host health. Chitosan (CS) possesses diverse biological and pharmacological effects and has been used as a new source of prebiotic. In this study, ERIC (Enterobacterial Repetitive Intergenic Consensus)-PCR and viable counts methods were combined to explore the prebiotic-like effects of CS on the intestinal microflora in mice. Mice were divided into 3 groups randomly, and treated with water, 1g/kg of CS, 0.25g/kg of CS, respectively for 24 days. Subsequently, they were treated with levofloxacin (65mg/kg) for 6 days. Viable counts method indicated the growth of Lactobacillus was promoted with CS treatment while at the same time Enterobacteria and Enterococcus were inhibited. ERIC-PCR fingerprint, UPGMA dendrogram, PCA and diversity analysis showed that the intestinal microflora composition was changed with antibiotics treatment, and that samples were significantly separated from those of the control and long-term CS-treated groups. Together, our results demonstrated that CS could be regarded as a potential food supplement for protecting intestinal microflora and regulate imbalance.

Cerebral small vessel diseases (CSVD), such as white matter hyperintensities (WMH), have been acknowledged as a cause of brain atrophy. However, the relationship between brain volumes and cerebral microbleeds (CMBs) has not yet been determined. We aimed to evaluate whether the presence and topography of CMBs are associated with altered volumes of gray matter (GMV) and white matter (WMV). Non-stroke and non-demented subjects were prospectively recruited from the I-Lan Longitudinal Aging Study. High-resolution 3-T MRI was performed to quantify total and regional WMV and GMV, including Alzheimer's disease-susceptible areas. CMBs were assessed with susceptibility-weighted imaging. Six hundred and fifty-nine subjects (62.1 ± 8.3 years, 290 (44%) men) were included. Thirty-two (4.9%) subjects had strictly lobar CMBs (SL-CMBs) and 51 (7.7%) had deep or infratentorial CMBs (DI-CMBs). We observed an association between CMBs and WMV, independent of age, sex, and vascular risk factors; the direction of association depended on the location of the CMBs. The SL-CMB group had an increased total, frontal, and occipital WMV compared with the no-CMB group, which remained significant after adjusting for other CSVDs (WMH volumes and lacune numbers). In contrast, the DI-CMB group had a decreased occipital WMV compared to the no-CMB group. However, this significance disappeared after taking other CSVDs into consideration. Our results showed no relationship between CMBs and GMV. In conclusion, the increased WMV in non-stroke, non-demented subjects with SL-CMBs observed here provides insight into the early pathogenesis of SL-CMBs. This may be a result of increased water content or amyloid accumulation.

Correction for 'The first two examples of halogen bonding with a sigma hole-donating fluorine in the C sp 3 -FO sp 3 interaction from polyfluorinated trans-dihalo-palladium(ii) di-substituted pyridine complexes' by Vijayanath Elakkat et al., Chem. Commun., 2019, DOI: .

Inflammation is closely related to oral squamous cell carcinoma (OSCC). However, its mechanism is still obscure. Toll-like receptor 2 (TLR2) plays an important role in oral chronic inflammatory diseases, but the role of TLR2 in OSCC is unclear. Here, we investigated the expression of TLR2 expression in OSCCs and examined the potential role of TLR2 in OSCC through its association with clinicopathological features and patient outcome. We used 4-nitroquinoline 1-oxide (4-NQO) to induce a tongue cancer model in TLR2-/- and wild type (WT) mice. Histological and clinical results both indicated that TLR2 played a protective role in oral tumorigenesis. The results of a cytometric bead array (CBA) indicated that TLR2 deficiency resulted in Th1 and Th2 cytokine abnormalities, especially Th2 abnormalities. Immunohistochemistry also showed that TLR2 deficiency increases the number of tongue-infiltrating M2 macrophages. Overall, our results demonstrated that TLR2 plays an important role in the prevention of oral tumorigenesis and affects the levels of Th2 cytokines and tongue-infiltrating M2 macrophages; therefore, it may be used to prevent the development of oral cancer., Competing Interests: None., (AJCR Copyright © 2019.)

The first two examples of halogen bonding in the Csp3-FOsp3 interaction have been both experimentally and theoretically proved for trans-[PdX2(3-HCF2CF2CH2OCH2py)2] complexes where X = Cl and Br. Both metal complexes with a Csp3-FOsp3 halogen bond have a σ hole donating fluorine.

Objective: Increased arterial pulsatility index (API), usually representative of distal vascular resistance, have been linked to cerebral small vessel disease. However, their relationship with cerebral microbleeds (CMBs) is less well-studied. The present study aimed to evaluate the relationship between CMBs and API. Methods: We cross-sectionally evaluated participants from a non-clinical stroke, non-demented community-based population. APIs of cervical internal carotid and vertebral arteries were measured by ultrasonography. CMBs were assessed by susceptibility-weighted-imaging on 3T magnetic resonance imaging (MRI). Subjects were classified according to CMB locations: deep/infratentorial (DI) or strictly lobar (SL) CMB groups. DI-CMB group also included subjects with simultaneous lobar CMBs. Results: Of the 681 subjects [62.2 (8.4) years, 43.5% men] included, CMBs were found in 92 (13.5%) subjects: 57 (8.4%) with DI-CMB and 35 (5.1%) with SL-CMB. The results showed that CMB location influenced their association with API. DI-CMB was significantly associated with elevated API of internal carotid arteries (β = 0.031; 95% confidence interval = 0.002-0.059; P = 0.03), while SL-CMB was significantly associated with elevated API of vertebral arteries (β = 0.050; 95% confidence interval = 0.006-0.094; P = 0.025) in multivariate analyses adjusting for age, sex, cardiovascular risk factors, white matter hyperintensities (WMH), and lacunes. Conclusion: Our study again emphasizes (1) the association between API and cerebral small vessel disease and (2) the pathogenic differences between DI- and SL-CMBs. Our results lead to the postulation that in the presence of CMBs without clinical dysfunction yet, insidious small vascular disorders might already occur with corresponding topography., (Copyright © 2019 Chou, Wang, Peng, Liu, Lee, Chen, Lin and Chung.)

The complete chloroplast genome (plastome) of Suaeda glauca , an annual halophytic herb, was determined in this study. The plastome was 149,807 bp in size, containing a large single-copy region (82,162 bp), a small single-copy region (18,191 bp), and two inverted repeats regions (24,727 bp). The overall GC content of this plastome was 36.5%. In total, 113 unique genes, including 79 protein-coding genes (PCGs), 30 tRNAs and 4 rRNAs, were annotated. Phylogenomic analysis showed that S. glauca was sister to other Suaeda species., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

High phosphate is linked to vascular calcification and endothelial dysfunction; however, its relationship with cerebral small-vessel diseases (CSVDs) is still unknown. Study subjects were prospectively recruited from the community-based I-Lan Longitudinal Aging Study. CSVDs including lacunes, white matter hyperintensities (WMHs), and cerebral microbleeds were evaluated using 3T magnetic resonance images. Multivariate analyses were performed to study the associations between circulatory phosphate level and the presence of CSVDs. In vitro experiments included human brain microvascular endothelial cell (HBMEC) studies and western blotting. The present study included 186 subjects (age [mean ± standard deviation, range] 64.7 ± 8.6, 50-86.8 years; 93 men). Multivariate analysis revealed that circulatory phosphate levels > 3.925 mg/dL were associated with severe WMH with an odds ratio of 3.7 (95% confidence interval = 1.3-10.6) independent of age, sex, traditional vascular risk factors, total cholesterol, renal function, or circulatory calcium level. The in vitro study revealed a downregulation of tight junction protein (zona occludens-1, occludin, and claudin-5) expression in HBMECs after 48 h of treatment with high phosphate (2.5/5 mM). We are the first to report a relationship between circulatory phosphate and CSVDs. Our results suggest that high circulatory phosphate level might be a novel risk factor for CSVD, possibly by impairing BBB structures.

Heat shock factor 1 (HSF1) is highly expressed in various malignancies and is a potential modulator of tumor progression. Emerging evidence suggests that HSF1 activation in stromal cells is closely related to poor patient prognosis. However, the role of HSF1 in oral squamous cell carcinoma (OSCC) remains elusive. We aimed to investigate the function of HSF1 in cancer-associated fibroblasts (CAFs) of the tumor microenvironment (TME) and in tumor development. In the present study, we found that HSF1 was highly expressed in both CAFs and tumor cells, and was significantly correlated with poor prognosis and overall survival. Moreover, HSF1 overexpression in CAFs resulted in a fibroblast-like phenotype of Cal27 cells, induced epithelial-mesenchymal transition (EMT), and promoted proliferation, migration and invasion in Cal27 cells. HSF1 knockdown attenuated features of CAFs and reduced EMT, proliferation, migration and invasion in Cal27 cells. Furthermore, HSF1 in CAFs promoted tumor growth in nude mice. Taken together, these data suggest that HSF1 expression in CAFs drive OSCC progression, and could serve as an independent prognostic marker of patients with OSCC. Thus, HSF1 is a potent mediator of OSCC malignancy., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)