Search

The ongoing COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a positive-stranded RNA genome. Current proteomic studies of SARS-CoV-2 mainly focus on the proteins encoded by its genomic RNA (gRNA) or canonical subgenomic RNAs (sgRNAs). Here, we systematically investigated the translation landscape of SARS-CoV-2, especially its noncanonical sgRNAs. We first constructed a strict pipeline, named vipep, for identifying reliable peptides derived from RNA viruses using RNA-seq and mass spectrometry data. We applied vipep to analyze 24 sets of mass spectrometry data related to SARS-CoV-2 infection. In addition to known canonical proteins, we identified many noncanonical sgRNA-derived peptides, which stably increase after viral infection. Furthermore, we explored the potential functions of those proteins encoded by noncanonical sgRNAs and found that they can bind to viral RNAs and may have immunogenic activity. The generalized vipep pipeline is applicable to any RNA viruses and these results have expanded the SARS-CoV-2 translation map, providing new insights for understanding the functions of SARS-CoV-2 sgRNAs.

Background: The Bosniak classification system based on contrast-enhanced computed tomography (CECT) is commonly used for the differential diagnosis of cystic renal masses. Contrastenhanced ultrasound (CEUS) is a relatively novel technique, which has gradually played an important role in the diagnosis of cystic renal cell carcinoma (CRCC) due to its safety and lowest price. Objective: The aim of the study is to investigate the application value of CEUS and Bosniak classification into the diagnosis of cystic renal masses. Method: 32 cystic masses from January 2018 to December 2019 were selected. The images of conventional ultrasound (US), CEUS and CECT from subjects confirmed by surgical pathology were retrospectively analyzed. The Bosniak classification system of cystic renal masses was implemented using CEUS and CECT, and the diagnostic ability was compared. Results: For the 32 cystic masses, postoperative pathology confirmed 11 cases of multilocular CRCC, 15 cases of clear cell carcinoma with hemorrhage, necrosis and cystic degeneration, 5 cases of renal cysts, and 1 case of renal tuberculosis. The Bosniak classification based on CEUS was higher than that based on CECT, and the difference was statistically significant (P = .024). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CEUS were comparable to CECT. There was no significant difference observed in the diagnosis of CRCC (P >.05). Conclusion: CEUS combined with Bosniak classification greatly improves the diagnosis of CRCC. CEUS shows a comparable diagnostic ability to CECT. In daily clinical routine, patients who require multiple examinations and present contraindications for CECT can particularly benefit from CEUS.

Background: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. Methods: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target

Aggregation-induced emission (AIE) nanoparticles have been widely applied in photodynamic therapy (PDT) over the past few years. However, amorphous nanoaggregates usually occur in their preparation, resulting in loose packing with disordered molecular structures. This still allows free intramolecular motions, thus leading to limited brightness and PDT efficiency. Herein, we report deep-red AIE nanocrystals (NCs) of DTPA-BS-F by following the facile method of nanoprecipitation. It is observed that DTPA-BS-F NCs possess not only a high photoluminescence quantum yield value of 8% in the deep-red region (600-850 nm) but also an impressive reactive oxygen species (ROS) generation efficiency of up to 69%. Moreover, DTPA-BS-F NCs targeting dual-organelles of lysosomes and nucleus to generate ROS are also achieved, thus boosting the PDT effect in cancer therapy both

Celastrol (CEL), a pentacyclic triterpene compound, has been proven to have a definite antipulmonary fibrosis effect. However, its direct targets for antipulmonary fibrosis remain unknown. In this study, we designed and synthesized a series of celastrol-based probes to identify the direct targets in human pulmonary fibroblasts using an activity-based protein profiling strategy. Among many fished targets, we identified a key protein, cullin-associated and neddylation-dissociated 1 (CAND1), which was involved in fibroblast-myofibroblast transformation (FMT). More importantly, we found that the inhibitory effect of celastrol on FMT is dependent on CAND1, through improving the interactions between CAND1 and Cullin1 to promote the activity of Skp1/Cullin1/F-box ubiquitin ligases. In silico studies and cysteine mutation experiments further demonstrated that Cys264 of CAND1 is the site for conjugation of celastrol. This reveals a new mechanism of celastrol against pulmonary fibrosis and may provide a novel therapeutic option for antipulmonary fibrosis.

The goal of this study was to look into age, genetics,sex, oral mucosa diseases, and systemic diseases as potential risk factors for the geographic tongue (GT) in a Chinese population.This retrospective cross-sectional study used the demographic and medical data of 3400 patients between March 2021 and August 2021 from the Department of Oral Medicine at West China Hospital of Stomatology. Binary logistic regression was conducted to analyze the association of GT and age, fissured tongue (FT), burning mouth syndrome (BMS), oral lichen planus (OLP), gastrointestinal disorders, and hematologic disorders and to acquire the adjusted odds ratio (AOR).GT occurred in 3.6% of patients, with 15 out of 123 (12.2%) patients with GT having a family history. Binary logistic regression found age30 years (AOR: 4.4; [95% CI: 2.8-6.9]), FT (28.8 [17.1-48.4]), BMS (0.3 [0.1-0.6]), OLP (0.2 [0.0-0.5]), and gastrointestinal disorders (4.3 [2.7-6.7]) were significantly associated with GT, and GT was unrelated to recurrent aphthous ulcer (RAU) or systemic diseases such as cardiovascular diseases.In the Chinese population, GT was more prevalent in patients with30 years of age, FT, and gastrointestinal disorders, and it was less prevalent in BMS and OLP.

Women with labial hypertrophy may opt for labiaplasty. The aim of the study was to analyze the complications, long-term follow-up of clinical outcomes and satisfaction in this population over the past 10 years.All women who underwent labiaplasty with or without clitoral hood reduction at our center between January 2008 and August 2020 were retrospectively identified. Retrospective study was conducted, recording follow-up outcomes, motivations, techniques, postoperative complications, reasons requiring reoperation, and surgical satisfaction concerned different clinical characteristics. A concrete analysis of each specific outcome and a detailed knowledge of these procedures were performed.A total of 52.41% reported functional impairment, 20.25% cited aesthetics complains, and 27.34% were motivated by both the previously mentioned reasons. Women undergoing surgical correction sometimes mixed with various psychological aspects. A total of 91.06% reported that they were moderately (6.04%) or extremely (85.02%) satisfied with the outcomes after surgery, and 37 (8.94%) reported dissatisfied. Revision surgery was needed in a small number of patients (n = 7 of 414 patients, 1.69%) because of undesirable appearance. The most common complication in our patients was asymmetry (6.28%). Women requested labiaplasty in the last 2 reasons or procedures or without psychological distress were more likely feel satisfied with the results (satisfaction rate90%). There was a significant difference in satisfaction among the 3 concerns as well as between the 2 kinds of psychological conditions ( P0.05). Satisfaction of patients with aesthetic complains compared with the other 2 worries was significantly lower ( P0.05). There was no significant difference among the 3 procedures in this comparison group ( P0.05). In addition, satisfaction in labiaplasty with or without clitoral hoodoplasty, neither of which was statistically different ( P0.05). Patients aged 30 to 39 years reported the lowest satisfaction in comparison with the other age groups.Labiaplasty of the labia minora is the most commonly performed genital cosmetic surgery procedure. This study on 414 patients demonstrated that it is associated with a high degree of patient satisfaction and low morbidity and provided evidence of safety and effectiveness preliminary, indicating that the procedure may be regarded as safe.

The objective of the study was to evaluate the effect of proximal parent artery stenosis on the hemodynamics of aneurysms in the internal carotid artery-posterior communicating artery (ICA-Pcom).A retrospective study of 74 patients with aneurysms in the ICA-Pcom who underwent treatment at the Department of Neurosurgery of Changhai Hospital was conducted between January and June 2018. Patients with proximal parent artery stenosis were included. Case-specific three-dimensional images were reconstructed, and software-based simulations of different stenosis morphologies were performed, focusing on stenosis severity and the distance from the aneurysm to the stenosis. The wall shear stress (WSS) of the aneurysms and blood flow velocity of the aneurysm neck plane were calculated. We performed simulations to evaluate the outcomes of postballoon angioplasty by considering a virtual operation group. To further assess whether WSS after balloon angioplasty increases the risk of aneurysm rupture, a control group of ruptured ICA-Pcom aneurysms without parent artery stenosis was matched with the virtual operation group based on sex, age, history of hypertension, and aneurysm size. Thereafter, the normalized WSS of the 2 groups was calculated.Eight patients with parent artery stenosis were included (2 men and 6 women; average age: 64 ± 15 years). The patients were divided into eccentric and concentric stenosis groups according to the stenotic morphologies, with 4 patients in each group. In both groups, the average WSS of the aneurysm and average blood flow velocity at the neck plane increased with the severity of parent artery stenosis, whereas the WSS did not correlate with distance. In the concentric stenosis group, the average blood flow velocity generally decreased as the distance between stenosis and aneurysm increased; however, no such trend was observed in the eccentric stenosis group. The normalized WSS of aneurysms after virtual balloon angioplasty was higher than that of the ruptured aneurysms (0.599 [0.548, 0.800] vs. 0.367 [0.324, 0.407]; P = 0.007).Intensified severity of proximal stenosis increases the blood flow velocity and aneurysmal WSS, which may lead to the progression of ICA-Pcom aneurysms. Treatment of the stenosis can reduce the WSS of aneurysms; however, its effect on the prognosis of ICA-Pcom aneurysms requires more concrete evidence.

An association between tumor necrosis factor (TNF)-α inhibitors and hypoglycemia has been detected in a few case reports and small case series; however, no relevant pharmacovigilance data have been published yet.The objective of this study was to detect and characterize relevant safety signals between hypoglycemia and TNF-α inhibitor use.Indication-focused disproportionality analysis was conducted to detect increased reporting of TNF-α-associated hypoglycemia compared with all other reports with the same indication during the same time period. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated to determine disproportionality. To reduce potential confounding factors, adjusted RORs were further calculated by logistic regression to control for age, sex, diabetes status, and concomitant drugs that potentially affect blood glucose levels.In all, 1086 adverse drug reactions related to TNF-α inhibitors were reported as 'hypoglycemia'. There were no disproportionality signals of hypoglycemia in TNF-α inhibitor users with indication of inflammatory bowel disease. When TNF-α inhibitors were considered as a class, disproportion for hypoglycemia only emerged in indication of psoriasis (n = 267, ROR 1.20, 95% CI 1.02-1.41). In further analyses of specific TNF-α inhibitor type, significant RORs for hypoglycemia were found in indication of rheumatic disease, including adalimumab in ankylosing spondylitis (n = 37, ROR 1.97, 95% CI 1.28-3.04), psoriasis (n = 160, ROR 1.64, 95% CI 1.37-1.97), and rheumatoid arthritis (n = 230, ROR 1.35, 95% CI 1.16-1.56) and infliximab in psoriasis (n = 18, ROR 2.14, 95% CI 1.33-3.42). After adjusting for confounding factors, only the signals of adalimumab were stable.Our study identified some potential pharmacovigilance signals between hypoglycemia and TNF-α inhibitors, which warrants further validation.

Virtual reality therapy (VRT) is a new psychotherapeutic approach integrating virtual reality technology and psychotherapy. This case series aimed to study effectiveness of VRT in treating psychological problems. We described four cases of first-line health care professionals with emerging clinically significant early psychological problems during the COVID-19 outbreak, and specifically received the VRT treatment. We compared the Patient Health Questionnaire 9 items (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), PHQ-15, and Athens Insomnia Scale to evaluate psychological symptoms and sleep quality before and after sessions. All four cases showed a reduction in scale comparison. General scores of the PHQ-9 reduced 65%, GAD-7 reduced 52.17%, PHQ-15 decreased 38.17%, and scores of the Athens Insomnia Scale reduced 67.44%. Meanwhile, a reduction in depression, anxiety, psychosomatic, and sleeping symptoms was also found, which decreased 76.92% in general. These results are highly significant statistically. This case series demonstrated the effectiveness of VRT on psychological problems as a promising approach to apply on various psychological distress and disorders.

Among numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concerns, Omicron is more infectious and immune-escaping, while Delta is more pathogenic. Here, we provide evidence for both intervariant and intravariant recombination of the rapidly evolving new SARS-CoV-2 genomes, including XD/XE/XF and BA.3, raising concerns of potential more infectious, immune-escaping, and disease-causing Omicron and Delta-Omicron variants.

On-demand designed theranostics nanoagents show promising applications for next-generation precision-and-personalized oncotherapy. Researchers have since aimed to develop nanoplatforms that can efficiently deliver drugs and contrast medium to tumor and release active ingredients in response to tumor microenvironment (TME) conditions. Herein, we propose a modular strategy, and develop a series of nanoplatforms based on metal-coordinated-polyprodrugs for cancer theranostics. The polyprodrugs were synthesized through a click-reaction between amino acid and doxorubicin (DOX) with dipropiolate. The backbones of the polyprodrugs had intrinsic sensitivities to pH and/or GSH, and provided abundant -COOH, -NH2, or -S-S- to chelate with functional metal ions and further self-assembled to form different morphologies. Dicysteine, which contains disulfide bond (-S-S-), was chosen to copolymerize with DOX and triethylene glycol dipropiolate (TEP) to prepare the pH/GSH dual-responsive polyprodrug poly(dicysteine-co-TEP-co-DOX) (pDTD), then separately coordinated with Gd3+, Fe3+, and Mn2+ to construct nanoplatforms pDTD@M (M representing the metal ions). In vitro and in vivo investigations suggest the metal-coordinated-polyprodrug nanoplatforms have good magnetic resonance imaging (MRI) ability and efficient tumor-growth inhibition with high safety. The design strategy of nanoplatforms based on metal-coordinated-polyprodrugs provides a new idea for on-demand construction of promising theranostics agents. STATEMENT OF SIGNIFICANCE: Compared to small molecule antitumor drugs, polymeric drugs have high drug loading ratio and are easily enriched at the tumor site to achieve improved therapy efficacy. This work utilizes click reactions to link amino acids with anticancer drugs to produce polymeric drugs that are degraded in response to tumor microenvironment and released small molecule antitumor drugs mainly in tumor sites, and subtly utilizes the coordination of amino acid to chelate MRI functional metal ion to realize enhanced MRI imaging mediated tumor therapy. This strategy provides a new idea for the convenient construction of polymeric drugs for tumor theranostics.

Brown and beige adipocytes dissipate energy in a nonshivering thermogenesis manner, exerting beneficial effects on metabolic homeostasis. CHCHD10 is a nuclear-encoded mitochondrial protein involved in cristae organization; however, its role in thermogenic adipocytes remains unknown. We identify CHCHD10 as a novel regulator for adipocyte thermogenesis. CHCHD10 is dramatically upregulated during thermogenic adipocyte activation by PPARγ-PGC1α and positively correlated with UCP1 expression in adipose tissues from humans and mice. We generated adipocyte-specific Chchd10 knockout mice (Chchd10-AKO) and found that depleting CHCHD10 leads to impaired UCP1-dependent thermogenesis and energy expenditure in the fasting state, with no effect in the fed state. Lipolysis in adipocytes is disrupted by CHCHD10 deficiency, while augmented lipolysis through ATGL overexpression recovers adipocyte thermogenesis in Chchd10-AKO mice. Consistently, overexpression of Chchd10 activates thermogenic adipocytes. Mechanistically, CHCHD10 deficiency results in the disorganization of mitochondrial cristae, leading to impairment of oxidative phosphorylation complex assembly in mitochondria, which in turn inhibits ATP generation. Decreased ATP results in downregulation of lipolysis by reducing nascent protein synthesis of ATGL, thereby suppressing adipocyte thermogenesis. As a result, Chchd10-AKO mice are prone to develop high-fat diet–induced metabolic disorders. Together, our findings reveal an essential role of CHCHD10 in regulating lipolysis and the thermogenic program in adipocytes.

Background: LC–MS/MS methods were developed for pharmacokinetic analysis and verified to measure fluoropezil, a new AchE inhibitor for Alzheimer's disease treatment, and its two primary metabolites ( N-debenzyl fluoride fluoropezil [M1] and N-oxidized fluoropezil [M11]) in human plasma. Methods & results: Analytes were extracted from 50 μl plasma using protein precipitation and separated by HPLC using a bridged ethyl hybrid column and gradient elution procedure. Analytical detection was performed with a triple quadrupole mass spectrometer and electrospray ionization source in multiple reaction monitoring mode. The LC–MS/MS method was fully validated. The quantification linear ranges were 0.100–50.0 ng/ml (fluoropezil), 0.0500–25.0 ng/ml (M1) and 0.0500–25.0 ng/ml (M11). Conclusion: A sensitive, reliable LC–MS/MS method was established and used successfully to explore the pharmacokinetics of fluoropezil.

Glioma originated from excessively proliferative and highly invaded glial cells is a common intracranial malignant tumor with poor prognosis. Resistance to temozolomide (TMZ) is a clinical challenge in glioma treatment due to the fact that chemoresistance remains a main obstacle in the improvement of drug efficacy. Salvianolic acid A (Sal A), originated from traditional Chinese herbal medicine

Despite its small size, the pituitary gland plays a central role in the maintenance of normal homeostasis of most physiological systems through its regulation of the function of other endocrine glands. The complexity of the anterior pituitary gland, due to its composition of several different hormone-secreting cell types, begets a plethora of disorders and pathologies due primarily to hyposecretion or hypersecretion of hormones. The gonadotrophs, which make up less than 5% of the total number of cells in the anterior pituitary, serve to regulate gonad development and sexual reproduction in males and females. Despite the increased research on the development of models to study pituitary function within the last decade, a model specifically designed to study the gonadotrophs is still lacking. The development of organoid technology has facilitated research in the field of personalized medicine and physiological testing using patient-derived cells. The ability to produce pituitary organoids would allow researchers to construct an in vitro model of the human hypothalamic-pituitary-gonadal or hypothalamic-pituitary-adrenal axis to use in further fertility or endocrine research. The application of this technology in patients could revolutionize the treatment of infertility and a variety of neuroendocrine disorders. The impetus behind this study was to develop a pituitary-like organoid consisting only of gonadotrophs. Despite the lack of success in differentiating gonadotrophs, pituitary-like organoids were differentiated from human-induced pluripotent stem cells. In addition, two-dimensional and three-dimensional differentiated cultures were characterized and compared to human adult cadaveric pituitary tissue.

Background: Cancer stem cells could influence tumor recurrence and metastasis. Objective: To develop a new effective treatment modality targeting breast cancer stem cells (BCSCs) and to explore the role of Apatinib in BCSCs. Methods: BCSCs were isolated from MDA-MB-231 cells by the immune magnetic beads method. BCSCs were treated with Apatinib, lentiviral plasmids (lncRNA ROR), and iCRT-3 (Wnt pathway inhibitors). Viability, colony numbers, sphere numbers, apoptosis, migration, invasion of BCSCs were detected by MTT, colony formation, tumorsphere, flow cytometry, wound-healing, transwell assays, respectively. The expressions of markers (ABCG2, CD44, CD90, and CD24), epithelial-mesenchymal transition (EMT)-related molecules (Ecadherin, N-cadherin, Vimentin, MMP-2, MMP-9), and Wnt/β-catenin pathway-related proteins (Wnt3a, Wnt5a, β-catenin) in breast cancer stem cells were determined by performing Western blot and qRT-PCR analysis. Results: Apatinib decreased the viability and colony numbers of BCSCs in a concentration-dependent manner, and it also reduced sphere numbers, suppressed migration, invasion and lncRNA ROR expression, and induced apoptosis of BCSCs. However, these results were partially reversed by lncRNA ROR overexpression. Apatinib suppressed stem property, EMT process, and Wnt/β-catenin pathway in BCSCs, which was partially reversed by lncRNA ROR overexpression. Moreover, lncRNA ROR overexpression increased the colony and sphere numbers and promoted the cell viability, apoptosis inhibition, migration, and invasion of BCSCs, but these effects were partially reversed by iCRT-3. LncRNA ROR overexpression increased the stem property, EMT process, and Wnt/β-catenin pathway, which were partially counteracted by iCRT-3. Conclusion: Apatinib inhibited stem property and malignant biological behaviors of BCSCs by blocking the Wnt/β-catenin signal pathway through down-regulating lncRNA ROR.

Post-treatment recurrence remains a challenge for the global control of tuberculosis (TB). This study investigated longitudinal data on pulmonary TB recurrence rates and risk factors for recurrence among successfully treated smear-positive tuberculosis cases in China.Between 1st January 2009 and 31st December 2016 we evaluated 33 441 treatment-naïve patients diagnosed with sputum-smear-positive, non-multidrug-resistant TB in Hangzhou, China. We included the data of 9828 patients with TB who were treated successfully.A total of 4.9% of the cases were recurrent (479/9828), identified within a median observation period lasting 1565 days. Altogether, 51.1% (245/479) of the recurrences occurred within 1 year. The cumulative 2- and 5-year recurrence rates were 3.90% (95% confidence interval (CI) 3.3-4.5%) and 5.4% (95%CI 4.8-6.0%), respectively. Prolonged treatment (over 7 months) occurred in 64.7% (6363/9828), with a median treatment duration of 242 days (interquartile range 195-348 days). Male sex (adjusted hazard ratio (aHR) (95%CI) 1.61 (1.30-2.00), p 0.001), age 60 years old or older (aHR (95%CI) 2.03 (1.70-2.44), p 0.001), pulmonary cavity (aHR (95%CI) 1.51 (1.25-1.82), p 0.001) and sputum positivity at 2 months (aHR (95%CI) 1.39 (1.05-1.81), p 0.02) all increased the risk of TB recurrence. Prolonged treatment was associated with reduced TB recurrence (aHR (95%CI) 0.73 (0.61-0.88), p 0.001).Recurrence remains a problem for successfully treated patients with sputum-smear-positive pulmonary TB, especially those with independent risk factors. Further analysis of prolonged treatment is required.

Gastric cancer is a global cancer with a high mortality rate. A growing number of studies have found the abnormal expression of lncRNA (long noncoding RNA) in many tumors, which plays a role in promoting or inhibiting cancer. Similarly, lncRNA abnormal expression plays an essential biological function in gastric cancer. This article focuses on lncRNA involvement in the development of gastric cancer in terms of cell cycle disorder, apoptosis inhibition, metabolic remodeling, promotion of tumor inflammation, immune escape, induction of angiogenesis, and Epithelial Mesenchymal Transition (EMT). The involvement of lncRNA in the development of gastric cancer is related to drug resistance, such as cisplatin and multi-drug resistance. It can also be used as a potential marker for the diagnosis and prognosis of gastric cancer and a target for the treatment. With an in-depth understanding of the mechanism of lncRNA in gastric cancer, new ideas for personalized treatment of gastric cancer are expected.

In mammals, cyclic GMP-AMP synthase (cGAS) recognizes cytosolic dsDNA to induce the type I IFN response. However, the functional role of cGAS in the IFN response of fish remains unclear or controversial. In this study, we report that cGAS orthologs from crucian carp Carassius auratus (CacGAS) and grass carp Ctenopharyngodon idellus (CicGAS) target the dsRNA sensor retinoic acid–inducible gene I (RIG-I) for negative regulation of the IFN response. First, poly(deoxyadenylic-deoxythymidylic) acid–, polyinosinic-polycytidylic acid–, and spring viremia of carp virus–induced IFN responses were impaired by overexpression of CacGAS and CicGAS. Then, CacGAS and CicGAS interacted with CiRIG-I and CiMAVS and inhibited CiRIG-I– and CiMAVS-mediated IFN induction. Moreover, the K63-linked ubiquitination of CiRIG-I and the interaction between CiRIG-I and CiMAVS were attenuated by CacGAS and CicGAS. Finally, CacGAS and CicGAS decreased CiRIG-I–mediated the cellular antiviral response and facilitated viral replication. Taken together, data in this study identify CacGAS and CicGAS as negative regulators in RIG-I–like receptor signaling, which extends the current knowledge regarding the role of fish cGAS in the innate antiviral response.

The Revised International Staging System (R-ISS) is a simple and powerful prognostic tool for multiple myeloma (MM). However, heterogeneity in R-ISS stage is still poorly characterised, hampering improvement of treatments. We used single-cell RNA-seq to examine novel cellular heterogeneity and regular networks in nine MM patients stratified by R-ISS. Plasma cells were clustered into nine groups (P1-P9) based on gene expression, where P1-P5 were almost enriched in stage III.PDIA6 was significantly upregulated in P3 and LETM1 was enriched in P1, and they were validated to be upregulated in the MM cell line and in 22 other patients' myeloma cells. Furthermore, in progression, PDIA6 was newly found and verified to be activated by UQCRB through oxidative phosphorylation, while LETM1 was activated by STAT1 via the C-type lectin receptor-signalling pathway. Finally, a subcluster of monocytes was exclusively found in stage III specifically expressed chemokines modulated by ATF3. A few ligand-receptor pairs (CCL3/CCL5/CCL3L1-CCR1) were obviously active in monocyte-plasma communications in stage III. Herein, this study identified novel molecules, networks and crosstalk pairs in different R-ISS stages of MM, providing significant insight for its prognosis and treatment.

During childhood, the ability to detect audiovisual synchrony gradually sharpens for simple stimuli such as flashbeeps and single syllables. However, little is known about how children perceive synchrony for natural and continuous speech. This study investigated young children's gaze patterns while they were watching movies of two identical speakers telling stories side by side. Only one speaker's lip movements matched the voices and the other one either led or lagged behind the soundtrack by 600 ms. Children aged 3-6 years (n = 94, 52.13% males) showed an overall preference for the synchronous speaker, with no age-related changes in synchrony-detection sensitivity as indicated by similar gaze patterns across ages. However, viewing time to the synchronous speech was significantly longer in the auditory-leading (AL) condition compared with that in the visual-leading (VL) condition, suggesting asymmetric sensitivities for AL versus VL asynchrony have already been established in early childhood. When further examining gaze patterns on dynamic faces, we found that more attention focused on the mouth region was an adaptive strategy to read visual speech signals and thus associated with increased viewing time of the synchronous videos. Attention to detail, one dimension of autistic traits featured by local processing, has been found to be correlated with worse performances in speech synchrony processing. These findings extended previous research by showing the development of speech synchrony perception in young children, and may have implications for clinical populations (e.g., autism) with impaired multisensory integration.

In the past decade, an increasing number of studies have found a relationship between the occurrence and development of depression and autoimmune diseases, and the high prevalence of depression in patients with connective tissue diseases has also been confirmed. Primary Sjögren's syndrome (pSS) is a chronic autoimmune exocrinopathy characterised by lymphocytic infiltration and exocrine gland destruction. Depression in pSS patients is common, and the factors contributing to this condition are complicated. pSS patients with depression generally have a lower quality of life than pSS patients without depression. Several pathophysiological mechanisms involved in the condition have been proposed in recent years. Thus, in this review, we summarised recent progress on the impact of depression on pSS patients' quality of life, the possible pathogenesis underlying the development of depression in pSS patients and the management of such patients.

Although osteosarcoma (OS) is the most common malignant bone tumor, the biological mechanism underlying its incidence and improvement remains unclear. This study investigated early diagnosis and treatment objectives using bioinformatics strategies and performed experimental verification.The top 10 OS hub genes-CCNA2, CCNB1, AURKA, TRIP13, RFC4, DLGAP5, NDC80, CDC20, CDK1, and KIF20A-were screened using bioinformatics methods. TRIP13 was chosen for validation after reviewing literature. TRIP13 was shown to be substantially expressed in OS tissues and cells, according to Western blotting (WB) and quantitative real-time polymerase chain reaction data. Subsequently, TRIP13 knockdown enhanced apoptosis and decreased proliferation, migration, and invasion in U2OS cells, as validated by the cell counting kit-8 test, Hoechst 33,258 staining, wound healing assay, and WB. In addition, the levels of p-PI3K/PI3K and p-AKT/AKT in U2OS cells markedly decreased after TRIP13 knockdown. Culturing U2OS cells, in which TRIP13 expression was downregulated, in a medium supplemented with a PI3K/AKT inhibitor further reduced their proliferation, migration, and invasion and increased their apoptosis.TRIP13 knockdown reduced U2OS cell proliferation, migration, and invasion via a possible mechanism involving the PI3K/AKT signaling pathway.

As our research on the physiopathology of intervertebral disc degeneration (IVD degeneration, IVDD) has advanced and tissue engineering has rapidly evolved, cell-, biomolecule- and nucleic acid-based hydrogel grafting strategies have been widely investigated for their ability to overcome the harsh microenvironment of IVDD. However, such single delivery systems suffer from excessive external dimensions, difficult performance control, the need for surgical implantation, and difficulty in eliminating degradation products. Stimulus-responsive composite hydrogels have good biocompatibility and controllable mechanical properties and can undergo solution-gel phase transition under certain conditions. Their combination with ready-to-use particles to form a multiscale delivery system may be a breakthrough for regenerative IVD strategies. In this paper, we focus on summarizing the progress of research on the stimulus response mechanisms of regenerative IVD-related biomaterials and their design as macro-, micro- and nanoparticles. Finally, we discuss multi-scale delivery systems as bioinks for bio-3D printing technology for customizing personalized artificial IVDs, which promises to take IVD regenerative strategies to new heights.

Chemoresistance is closely related to the therapeutic effect and prognosis in breast cancer patients. Increasing evidences demonstrated that RNA binding proteins (RBPs) have notable roles in regulating cancer cell proliferation, metastasis and chemotherapeutic sensitivity. RNA binding motif single stranded interacting protein 2 (RBMS2), an RBP, has been considered to be a tumor suppressor in several cancers. However, its role of doxorubicin sensitivity in breast cancer patients has not yet been fully revealed. Here, we performed doxorubicin cytotoxicity assay, flow cytometry and mouse xenograft model to examine the influence of RBMS2 on doxorubicin sensitization

Hypoglycemia induced by direct-acting antiviral agents (DAAs) for chronic hepatitis C virus (HCV) infection is a rare but potentially life-threatening adverse reaction, which led to warnings by competent authorities. We therefore aimed to examine the hypoglycemic safety signal for DAAs.Reports to the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 1 October 2012 to 31 March 2020 were analyzed. The Medical Dictionary for Regulatory Activities was used to identify hypoglycemia cases. A case by non-case disproportionality approach was used whereby reporting odds ratio (ROR) with 95% confidence intervals (CI) were calculated.In HCV infection with diabetes patients, the cumulative frequency of hypoglycemic ADRs was 21.85/1000 for reports involving DAAs versus 13.50/1000 for reports involving other medications; For DAAs as a class drug, a nearly double increased reporting odds for hypoglycemia was observed (ROR: 1.63, 95% CI: 1.11-2.41). However, in DAAs subgroup analysis, only telaprevir (ROR: 1.66, 95% CI: 1.01-2.74) and elbasvir/grazoprevir (ROR: 2.25, 95% CI: 1.05-4.83) were associated with increased reporting risk of hypoglycemia during corresponding marketing period; when combined with insulins and sulfonylureas, DAAs were associated with increased reporting risk for hypoglycemia (ROR: 1.98, 95% CI: 1.36-2.88; ROR: 1.62, 95% CI: 1.06-2.48), but concomitant biguanides, dipeptidyl peptidase IV (DPP-4) inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1RAs) were not significant.This study supports the current recommendation for cautious about hypoglycemic risk relating to the use of DAAs. Treatment with DAAs and antidabetic agents (especially insulins and sulfonylureas) will increase hypoglycemia reporting risk. Physicians and pharmacists should be aware of this risk when prescribing DAAs for patients suffering from diabetes, advanced age or liver decompensation.

To explore the efficacy and safety of Zhuang medicine medicated thread moxibustion (ZMTM) on psoriasis vulgaris.A multicenter, randomized, parallel controlled clinical trial was designed. A total of 241 outpatients with psoriasis vulgaris were randomly divided into a control group (120 cases) and a treatment group (121 cases) using a central block randomization from June 2015 to May 2018. The control group was treated with Western medicines alone including pidotimod dispersible tablets, vitamin B compound tablets, and compound cod liver oil-zinc oxide ointment. The treatment group was treated with ZMTM every 2 days combined with Western medicines. The two groups received continuous intervention for 30 days. The primary outcome was Psoriasis Area and Severity Index (PASI), and the secondary outcomes included Itch Rating Scale, Dermatology Quality of Life Index (DLQI), Hamilton Anxiety Rating Scale (HAMA), as well as PASI response rate. Meanwhile, adverse events were evaluated during the whole clinical trial. Follow-up was carried out 30 days after treatment.There were 5 cases of shedding in this trial. In intention-to-treat analysis, 236 cases were included and each group contained 118 cases. On the 30th and 60th days, PASI scores of patients in each group were significantly lower than that at baseline (P0.01) and the PASI score reduction of the treatment group was greater than that of the control group (P0.01). Itch Rating Scale, DLQI, and HAMA scale were decreased in both groups after treatment, and the treatment group showed a better therapeutic effect (P0.01). The response rates of PASI 50 and 75 were significantly higher than those in the control group [81.4% (96/118), 43.2% (51/118) vs. 41.5% (49/118), 11.0% (13/118), respectively, P0.05]. During follow-up, the improvements in scores of PASI, Itch Rating Scale, DLQI, and HAMA of the treatment group were significantly greater than those of the control group (P0.01). The response rates of PASI 50 and 75 in the treatment group were significantly higher than those in the control group, respectively (both P0.05). No obvious adverse reaction was found in either group.ZMTM combined with Western medicines showed a better therapeutic effect in the treatment of psoriasis vulgaris without obvious adverse reaction. (Trial Registration No. ChiCTR-IOR-16008159).

Differentiation of standing and walking based on plantar pressures is helpful in developing strategies to reduce health risks in the workplace. In order to improve the differentiation ability, the paper proposes a new metric for posture differentiation, that is, the pressure ratio on the two anatomical plantar regions. The plantar pressures were collected from 30 persons during walking and standing. After verifying the normal distribution of the pressure ratio by the Monte Carlo method, two-way repeated-measures ANOVA was conducted for the pressure ratios. The advantage of the pressure ratio over two conventional pressure metrics (the average pressure and the peak pressure) is demonstrated by its much larger size effect. Furthermore, the pressure ratio permits to establish value ranges corresponding to walking and standing, which are less influenced by specific person factors, thus facilitating the design of a standardized posture recognition system. The underlying mechanism underlying the pressure ratio is discussed from the aspect of biomechanics of movement.

Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy. Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32). Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032). This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.

Introduction Arctigenin, derived from Arctium lappa L., has multiple pharmacological activities, including immunoregulatory, anti-diabetic, anti-tumor, and neuroprotective effects. Nevertheless, the potential therapeutic target of arctigenin in modulating inflammation remains undefined. Objectives In the present study, we identified that arctigenin was a phosphodiesterase-4 (PDE4) selective inhibitor for the first time. Further investigations were performed to fully uncover the effects and mechanism of arctigenin on experimental murine psoriasis model. Methods Crystal structure determination, PDEs enzyme assay, and isothermal titration calorimetry were included to illustrate the binding specialty, inhibitory effects, and selectivity of arctigenin on PDE4D. The anti-inflammatory effects were conducted in LPS-activated human peripheral blood mononuclear cells (PBMCs) and RAW264.7 cells. Imiquimod-induced murine psoriasis was performed to uncover the therapeutic effects and mechanism of arctigenin in vivo. Results Arctigenin could bind to the catalytic domain of PDE4D via formation of hydrogen bonds as well as π-π stacking interactions between the dibenzyl butyrolactone of arctigenin and several residues of PDE4D. Accordingly, arctigenin showed prominent anti-inflammation in human PBMCs and murine RAW264.7 cells. PDE4 inhibition by arctigenin resulted in elevation of intracellular cyclic adenosine monophosphate (cAMP) and phosphorylation of cAMP-response element binding protein (CREB), which were largely blocked through intervention of protein kinase A (PKA) activity by H89 treatment or reduction of protein expression by siRNA transfection. Moreover, we first identified that a topical application of arctigenin ameliorated experimental psoriatic manifestations in imiquimod-induced murine psoriasis model by decreasing adhesion and chemotaxis of several inflammatory cells. Further proteomics analysis revealed that arctigenin could rectify the immune dysfunction and hyperactivation of keratinocytes in the inflamed skin microenvironments, which might be largely related to the expression of Keratins. Conclusion The research provided credible clew that inhibition of PDE4 by arctigenin might function as the potential therapeutic approach for the treatment of psoriasis.

Juvenile systemic lupus erythematosus (JSLE) and juvenile idiopathic arthritis (JIA) are two common types of autoimmune diseases in children with unclear pathogenesis. Both peptidyl arginine deiminase type IV (PADI4) and interleukin 33 (IL-33) are the key molecular involved in immune responses in autoimmune diseases. Usually, it may share the same risk genetic alleles for autoimmune diseases.So measurement of PADI4 and IL-33 polymorphisms was conducted with 303 healthy controls, 144 JSLE patients and 160 JIA patients in this study.It demonstrated that there was a significant association between PADI4 genotypes (rs2240340: CT, CT + CC), IL-33 genotype (rs1929992: TT) and JSLE susceptibility in Southwest China population. While no significant association with the risk of JIA were observed no matter at allelic or genotypic levels.Our study reveals the importance of PADI4 and IL-33 polymorphisms with JSLE risk and their roles in the development of the diseases need more further researches.

Near-infrared (NIR) synaptic devices integrate NIR optical sensitivity and synaptic plasticity, emulating the basic biomimetic function of the human visual system and showing great potential in NIR artificial vision systems. However, the lack of semiconductor materials with appropriate band gaps for NIR photodetection and effective strategies for fabricating devices with synaptic behaviors limit the further development of NIR synaptic devices. Here, a two-terminal NIR synaptic device consisting of the In

Background Identifying polymorphism clades on phylogenetic trees could help detect punctual mutations that are associated with viral functions. With visualization tools coloring the tree, it is easy to visually find clades where most sequences have the same polymorphism state. However, with the fast accumulation of viral sequences, a computational tool to automate this process is urgently needed. Results Here, by implementing a branch-and-bound-like search method, we developed an R package named sitePath to identify polymorphism clades automatically. Based on the identified polymorphism clades, fixed and parallel mutations could be inferred. Furthermore, sitePath also integrated visualization tools to generate figures of the calculated results. In an example with the influenza A virus H3N2 dataset, the detected fixed mutations coincide with antigenic shift mutations. The highly specificity and sensitivity of sitePath in finding fixed mutations were achieved for a range of parameters and different phylogenetic tree inference software. Conclusions The result suggests that sitePath can identify polymorphism clades per site. The clustering of sequences on a phylogenetic tree can be used to infer fixed and parallel mutations. High-quality figures of the calculated results could also be generated by sitePath.

Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.

Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of α-HCoVs S proteins, we isolated a panel of antibodies against the HCoV-229E S protein and characterized their epitopes and neutralizing potential. We found that the N-terminal domain of HCoV-229E S protein is antigenically dominant wherein an antigenic supersite is present and appears conserved in HCoV-NL63, which holds potential to serve as a pan-α-HCoVs epitope. In the receptor binding domain, a neutralizing epitope is captured in the end distal to the receptor binding site, reminiscent of the locations of the SARS-CoV-2 RBD cryptic epitopes. We also identified a neutralizing antibody that recognizes the connector domain, thus representing the first S2-directed neutralizing antibody against α-HCoVs. The unraveled HCoVs S proteins antigenic similarities and variances among genera highlight the challenges faced by pan-HCoV vaccine design while supporting the feasibility of broadly effective vaccine development against a subset of HCoVs.

Objective: The expression of cytoskeleton-related protein γ-adducin (ADD3) was abnormally reduced in some tumors. Functional experiments demonstrated that it could inhibit the malignant progression of lung cancer and glioma, whereas the involvement of ADD3 in osteosarcoma was not clear. This study aimed to investigate the role of ADD3 in osteosarcoma and its upstream regulatory mechanisms. Methods: ADD3 was knocked down by siRNA transfection and the expression level of ADD3 was determined using quantitative real-time PCR assay and Western blot. CCK-8 assay and colony formation were performed to detect the capacity of cell proliferation. Transwell assay and PI and Annexin V-FITC staining were used to determine cell migration and apoptosis, respectively. Luciferase reporter experiment was performed to investigate the interaction between ADD3 and miR-23b-3p. Results: Based on gene silencing assays, we showed that knockdown of ADD3 suppressed apoptosis and promoted the proliferation and migration of osteosarcoma cells, revealing inhibitory effects of ADD3 in osteosarcoma. Luciferase reporter gene assays confirmed that miR-23b-3p could bind to the 3'-UTR of ADD3. Upregulation of miR-23b-3p not only inhibited the expression of ADD3, but also released the tumor suppressive role of ADD3 on the proliferation and migration of osteosarcoma cells. Conclusions: Our study found that ADD3 functioned as a tumor suppressor gene during osteosarcoma development. The abnormal upregulation of miR-23b-3p targeted the expression of ADD3 and resulted in accelerated osteosarcoma cell proliferation and migration. Thus, the miR-23b-3p/ADD3 axis contributes to the development of osteosarcoma and ADD3 is a key driver of malignancy.

Family members are critical mediators of the experiences of transgender people. We studied whether transgen-der subjects had disclosed their identity to their families and their families' reactions after the disclosure. We also evaluated the subjects' mental state and its association with disclosure status. Transgender people were recruited for this anonymous questionnaire survey in the Okayama University Hospital gender clinic. Subjects disclosed their identity to family members at the following rates: 68.7% to the father, 89.1% to the mother, 59.1% to a brother, 77.8% to a sister, and 47.6% to grandparents. Fathers had the lowest rate (26.7%) of posi-tive reactions, while over 50% of fathers showed an ambiguous response. Approximately 20% of parents showed a negative response. The majority of parents agreed to hormonal treatment and sex-reassignment sur-gery and that the transgender child should live with the gender they wanted to express. However, the rate of subjects with mood and anxiety disorders according to the Kessler 6 scale was significantly higher in those who experienced negative or ambiguous reactions from family members compared to those who experienced posi-tive reactions. Educational and mental health professionals should support the disclosure process of transgen-der people as well as their family members.

Background This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. Method RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan–Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25–0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.

Pollen allergy has already been an increasingly prominent ecosystem disservice in tourism attractions. However, few studies have assessed the tourist risk of pollen allergy through integrating multidisciplinary knowledge of ecology, medicine, phenology, and risk management. Basing on the conceptual framework of risk assessment proposed by UNISDR, we first established an index system of pollen-allergy risk for tourists in attractions and outlined assessment methods 18 available indexes were put forward to cover three aspects: hazard of plant allergen, tourist vulnerability, and resilience of assessment units. Subsequently, taking the Summer Palace as the case study area, we conducted a tourist risk assessment of pollen allergy. Values of nine available indexes were obtained via ecological investigation, phenological observation, and data mining of visitors' logs on Sina Weibo. Risk levels of spring pollen allergy for tourists in different assessment units were revealed by combining the green zone allergenicity index model and three-dimensional risk assessment matrix. The results showed that: (1) There were seven primary pollen-allergenic plants in the Summer Palace, including Platycladus orientalis, Sabina chinensis, Salix babylonica, Pinus tabulaeformis, Populus tomentosa Carr, Morus alba L. and Fraxinus chinesis, among which Platycladus orientalis and Salix babylonica were the highest allergenic. (2) Among 18 spots, tourists faced the highest risk level of pollen allergy in spring at three spots, namely the Hall of Serenity, Hall of Benevolence and Longevity, and Gallery of Literary and Prosperity. (3) The two routes of the Long Corridor and Longevity Hill scored high on the risk level. (4) Among four areas, risk levels of the Front-hill and Rear-hill areas were high. Given the increasing spatial-temporal uncertainty of pollen allergy and tourist behaviors under global warming and urbanization, the related monitoring should be strengthened in the future. Furthermore, the dynamic and improved assessment of pollen-allergy risk should be institutionalized and be integrated into the evaluation of tourism experience quality. Tourism administration should make full use of relevant assessment results and conduct more effective risk communication.

In this work, indoxyl-glucoside was used as the substrate to develop a cost-effective, paper-based analytical device for the fluorescent and colorimetric dual-mode detection of β-glucosidase activity through a smartphone. The β-glucosidase can hydrolyze the colorless substrate indoxyl-glucoside to release indoxyl, which will be self-oxidized to generate green products in the presence of oxygen. Meanwhile, the green products emit bright blue-green fluorescence under ultraviolet–visible light irradiation at 365 nm. Fluorescent or colorimetric images were obtained by a smartphone, and the red-green-blue channels were analyzed by the Adobe Photoshop to quantify the β-glucosidase activity. Under the optimum conditions, the relative fluorescent and colorimetric signals have a good linear relationship with the activity of β-glucosidase, in the range of 0.01–1.00 U/mL and 0.25–5.00 U/mL, and the limits of detection are 0.005 U/mL and 0.0668 U/mL, respectively. The activities of β-glucosidase in a crude almond sample measured by the fluorescent and colorimetric methods were 23.62 ± 0.53 U/mL and 23.86 ± 0.25 U/mL, respectively. In addition, the spiked recoveries of normal human serum and crude almond samples were between 87.5% and 118.0%. In short, the paper-based device, combined with a smartphone, can provide a simple, environmentally friendly, and low-cost method for the fluorescent and colorimetric dual-mode detection of β-glucosidase activity.

This retrospective study aimed to explore the effects of goal-oriented nursing intervention (GONI) on postpartum depression (PPD). We retrospectively analyzed the medical records of 72 women with PPD. They were allocated to a treatment group (n = 36, exercise plus GONI) or a control group (n = 36, exercise). Patients in both groups received a total of 3 months of treatment. Outcomes included the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score, HAMD-17 response rate (≥50% score reduction), HAMD-17 remission rate (score ≤ 7), and adverse events. Outcomes were analyzed before and after 3-month of treatment. After treatment, patients in the treatment group achieved more effective outcomes in the HADM-17 total score (P .01), HADM-17 response rate (P .01), HADM-17 remission rate (P .01) than those in the control group. Regarding safety, the medical records of both the groups did not report any adverse events. The results of this study showed that GONI and exercise had more effects in patients with PPD. Further prospective studies are required to validate our findings.

Depression is a globally widespread disorder caused by a complicated interplay of social, psychological, and biological factors. Approximately 280 million people are suffering from depression worldwide. Traditional frontline antidepressants targeting monoamine neurotransmitters show unsatisfactory effects. The development and application of novel antidepressants for dissimilar targets are on the agenda. This review characterizes the antidepressant effects of multiple endogenous compounds and/or their targets to provide new insight into the working mechanism of antidepressants. We also discuss perspectives and challenges for the generation of novel antidepressants.

In this study, we examined the quality of Puhui early education services perceived by Chinese teachers with evidence from a national validation study. Firstly, using a stratified cluster sampling method, the Puhui Early Education Service Quality Scale (PEESQ) was developed and validated with 994 Chinese teachers. Secondly, the psychometric properties indicated that PEESQ is a reliable and valid scale with three dimensions: service adequacy, service balance, and public service welfare. Thirdly, descriptive statistics found that Chinese teachers generally appreciated the quality of Puhui services, ranking the construct of “public welfare” the highest and “service balance” the lowest. Finally, hierarchical regression analysis found that urbanicity positively predicted teacher evaluations after controlling for demographic and kindergarten factors. The findings imply that more funding support and policy attention should be provided to help enhance the quality of Puhui early education services (EES). Moreover, this study extends the framework of research on teacher evaluation of EES and provides useful tools to evaluate universal EES in China and beyond.

Numerous studies have implicated Gα-interacting, vesicle-associated protein (GIV) in the development and metastasis of various cancers. However, its role remains unclear in liver hepatocellular carcinoma (LIHC). We aimed to demonstrate the relationship between GIV and LIHC based on The Cancer Genome Atlas database. We use the Gene Expression Profiling Interactive Analysis and UALCAN to explore the expression of GIV and the survive analysis of GIV in patients with LIHC, genetic alteration analysis, immune infiltration analysis, functional enrichment, protein-protein interaction network analyses, and transcription factor targets of GIV-correlated genes and GIV-interacting genes were performed this study. GIV expression was significantly elevated in LIHC tissues. Remarkable correlation was established between GIV expression and LIHC pathological stage. Low expression of GIV in tumor tissues had a better prognosis than GIV-high expression. GIV alteration frequency was 1.44% in patients with LIHC. GIV-unaltered patients had better survival than GIV-altered ones. Moreover, GIV expression level in LIHC significantly correlated with the infiltration level of immune cells and cancer-associated fibroblasts. The functions of differentially expressed GIVs are associated with the cell cycle pathway. Our data imply that E2F4, E2F1, MYC, and MYCN are key transcription factors for GIV-correlated genes and GIV-interacted genes. GIV may be an adverse prognostic factor for patients with LIHC; it also can be a potential therapeutic target against LIHC. Further studies are required to validate our findings.

OBJECTIVE: To investigate the clinical features of electronic laryngoscope in the diagnosis of senile voice diseases. METHODS: Elderly patients who visited the outpatient department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital from September 2014 to September 2018 were collected. All patients came in with hoarseness. All patients were routinely diagnosed by electronic laryngoscopy and the results were analyzed. RESULTS: A total of 1330 elderly patients aged 60 years and over were enrolled in this study, including 924 males and 406 females. There are significant differences in the distribution of various voice diseases in different genders(P < 0.05). Among male elderly patients, the top three were: 239 cases of throat malignant tumor(25.87%), 182 cases of vocal cord benign proliferative disease(19.70%), 147 cases of vocal cord leukoplakia(15.91%). Among female elderly patients, the top three diseases were: 183 cases(45.07%) of vocal cord benign proliferative disease, 70 cases(17.24%) of laryngitis, 66 cases(16.26%) of vocal cord paralysis. There were significant differences in the distribution of different voice disorders among the three different age groups of elderly patients. The top three elderly patients aged 60-69 years were: 298 cases(35.06%) of vocal cord benign proliferative diseases, 132 cases(15.53%) of laryngopharyngeal malignant tumors, 104 cases(12.24%) of vocal cord paralysis. The top three elderly patients aged 70-79 years were: 91 cases(24.20%) of laryngopharyngeal malignant tumors, 57 cases(15.16%) of vocal cord benign proliferative diseases, 55 cases(14.63%) of vocal cord paralysis. The top three elderly patients aged 80 years and above were: 25 cases(24.04%) of laryngopharyngeal malignant tumors, 21 cases(20.19%) of vocal cord paralysis, 16 cases(15.38%) of the vocal cords are not closed completely. There were also significant differences in the distribution of various voice diseases among smokers(P < 0.05). CONCLUSION: With the acceleration of the aging of society, we should pay more attention to the voice of the elderly. The most common disease in elderly women with hoarseness is benign hyperplastic vocal cord disease. The high incidence of laryngeal malignant tumors in elderly male hoarseness patients who smoke should be paid special attention to. Electronic laryngoscope plays an important role in the diagnosis of voice diseases in elderly patients.

Coaching style is key to athletes’ performance and mental well-being. However, few attempts have examined the effects of coaching style on athletes in a Chinese cultural context. Based on previous literature and 23 expert interviews (11 with athletes and 12 with coaches), we rebuilt a 16-items on the Controlling Coach Behaviors Scale. In study 1, 130 provincial team athletes completed a 16-items questionnaire on controlling coach behaviors. The questionnaire items were then screened using exploratory factor analysis and transformed into a formal scale. In study 2, another 560 provincial athletes completed several measures related to coaching style, motivation, subjective vitality, and burnout, and systematic tests were carried out to validate the scale. Study 3 examined the test-retest reliability of the Controlling Coach Behaviors Scale over a 2-week interval. Finally, the present study yielded a nine-item Controlling Coach Behaviors Scale with three dimensions (controlling use of reward, negative conditional regard, and excessive personal control). It suggests that cultural differences played an important role in the communication between athletes and coaches. The new Controlling Coach Behaviors Scale shows good validity and can be used in future research.