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Yusheng Cheng,* Xiongwen Tu,* Linlin Pan, Shuai Lu, Ming Xing, Linlin Li, Xingwu Chen Department of Respiratory Medicine, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China *These authors contributed equally to this work Purpose: Chronic bronchitis (CB), emphysematous (EM) and asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) phenotypes in COPD are well recognized. This study aimed to investigate distinguishing characteristics of these phenotypes in COPD patients with frequent exacerbations (FE).Patients and methods: A retrospective study was carried out. COPD patients with acute exacerbations were consecutively reviewed from November 2015 to October 2016. Patients were divided into FE and infrequent exacerbations (iFE) subgroups.Results: A total of 142 eligible COPD subjects were reviewed. In the CB phenotype subgroup, age, body mass index, forced expiratory volume in 1 second (FEV1) % predicted, COPD assessment test (CAT), modified Medical Research Council breathlessness measurement (mMRC) dyspnea scale, emphysema scores and arterial carbon dioxide pressure (PaCO2) were significantly different in subjects with FE when compared to those in subjects with iFE of CB. In the EM phenotype subgroup, age, CAT, mMRC scores and history of COPD were different in subjects with FE when compared to those in CB subjects with iFE. Multivariate analysis indicated that FEV1% predicted (odds ratio [OR] =0.90, P=0.04) and PaCO2 (OR =1.22, P=0.02) were independent risk factors for FE in COPD with CB phenotype, and CAT (OR =2.601, P=0.001) was the independent risk factor for FE in COPD with EM phenotype. No significant differences in characteristics were observed in ACOS phenotype subgroups with FE or iFE.Conclusion: In CB or EM phenotypes, COPD patients with FE present several differential clinical characteristics compared to patients with iFE, while the characteristics of ACOS phenotype in patients with FE need more investigation. Keywords: chronic bronchitis, emphysema, ACOS, COPD, frequent exacerbations

Aircraft measurements, including non-methane hydrocarbons (NMHCs), long-lived halocarbons, carbon monoxide (CO), and ozone (O3) collected on board the NASA DC-8 during the Deep Convection, Clouds, and Chemistry (DC3) field campaign (May – June 2012), were used to investigate interactions and mixing between stratospheric intrusions and polluted air masses. Stratospherically influenced air masses were detected using a suite of long-lived halocarbons, including chlorofluorocarbons (CFCs) and HCFCs, as a tracer for stratospheric air. A large number of stratospherically influenced samples were found to have reduced levels of O3 and elevated levels of CO (both relative to background stratospheric air), indicative of mixing with anthropogenically influenced air. Using n-butane and propane as further tracers of anthropogenically influenced air, we show that this type of mixing was present both at low altitudes and in the upper troposphere (UT). At low altitudes, this mixing resulted in O3 enhancements consistent with those reported at surface sites during deep stratospheric intrusions, while in the UT, two case studies were performed to identify the process by which this mixing occurs. In the first case study, stratospheric air was found to be mixed with aged outflow from a convective storm, while in the second case study, stratospheric air was found to have mixed with outflow from an active storm occurring in the vicinity of a stratospheric intrusion. From these analyses, we conclude that deep convective events may facilitate the mixing between stratospheric air and polluted boundary layer air in the UT. Throughout the entire DC3 study region, this mixing was found to be prevalent: 72% of all samples that involve stratosphere-troposphere mixing show influence of polluted air. Applying a simple chemical kinetics analysis to these data, we show that during DC3, the instantaneous production of hydroxyl radical (OH) in these mixed stratospheric-polluted air masses was 11 ± 8 times higher than that of stratospheric air, and 4.2 ± 1.8 times higher than that of background upper tropospheric air.

Emission of bromine from sea-salt aerosol, frost flowers, ice leads, and snow results in the nearly complete removal of surface ozone during Arctic spring. Regions of enhanced total column BrO observed by satellites have traditionally been associated with these emissions. However, airborne measurements of BrO and O3 within the convective boundary layer (CBL) during the ARCTAS and ARCPAC field campaigns at times bear little relation to enhanced column BrO. We show that the locations of numerous satellite BrO "hotspots" during Arctic spring are consistent with observations of total column ozone and tropopause height, suggesting a stratospheric origin to these regions of elevated BrO. Tropospheric enhancements of BrO large enough to affect the column abundance are also observed, with important contributions originating from above the CBL. Closure of the budget for total column BrO, albeit with significant uncertainty, is achieved by summing observed tropospheric partial columns with calculated stratospheric partial columns provided that natural, short-lived biogenic bromocarbons supply between 5 and 10 ppt of bromine to the Arctic lowermost stratosphere. Proper understanding of bromine and its effects on atmospheric composition requires accurate treatment of geographic variations in column BrO originating from both the stratosphere and troposphere. Copyright 2010 by the American Geophysical Union.

Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of the radix of Paeonia suffruticosa, has been reported to have a beneficial effect in prevention and treatment of cardiovascular diseases. Vascular cell adhesion molecule-1 (VCAM-1), plays a crucial role in case of early inflammatory responses, including atherosclerosis. In this study, we investigated the effect of paeonol on TNF-alpha-induced VCAM-1 expression in rat aortic endothelial cells (RAECs). The VCAM-1 expression in paeonol treated RAECs was measured. Paeonol inhibited TNF-alpha-induced VCAM-1 expression in a concentration-dependent manner. TNF-alpha induced p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) activities that contributed to VCAM-1expression was obviously attenuated after pre-treating RAECs with paeonol. The decrease of VCAM-1 expression by paeonol pretreatment led to a reduction of monocytes adhesion to RAECs. Taken together, our results demonstrated that paeonol inhibited VCAM-1 expression by the attenuation of p38 and ERK1/2 signal transduction pathways. We concluded that paeonol had the potential therapeutic development for use in anti-inflammatory and vascular disorders. [ABSTRACT FROM AUTHOR]

Hemipteran insects transmit viruses when infesting plants, during which vectors activate salicylic acid (SA)-regulated antiviral defenses. How vector-borne plant viruses circumvent these antiviral defenses is largely unexplored. During co-infections of begomoviruses and betasatellites in plants, betasatellite-encoded βC1 proteins interfere with SA signaling and reduce the activation of antiviral resistance. βC1 inhibits SA-induced degradation of NbNPR3 (Nicotiana benthamiana nonexpressor of pathogenesis-related genes 3), a negative regulator of SA signaling. βC1 does not bind directly to NbNPR3, but regulates NbNPR3 degradation via heat shock protein 90s (NbHSP90s). NbHSP90s bind to both NbNPR3 and βC1 and suppress SA signaling. This viral success strategy appears to be conserved as it is also documented for viral proteins encoded by two aphid-borne viruses. Our findings reveal an exquisite mechanism that facilitates the persistence of vector-borne plant viruses and provide important insights into the intricacies of the virus life cycle., (© 2024. The Author(s).)

Insect vector-virus-plant interactions have important ecological and evolutionary implications. The constant struggle of plants against viruses and insect vectors has driven the evolution of multiple defense strategies in the host as well as counter-defense strategies in the viruses and insect vectors. Cotton leaf curl Multan virus (CLCuMuV) is a major causal agent of cotton leaf curl disease in Asia and is exclusively transmitted by the whitefly Bemisia tabaci. Here, we report that plants infected with CLCuMuV and its betasatellite CLCuMuB enhance the performance of the B. tabaci vector, and βC1 encoded by CLCuMuB plays an important role in begomovirus-whitefly-tobacco tripartite interactions. We showed that CLCuMuB βC1 suppresses the jasmonic acid signaling pathway by interacting with the subtilisin-like protease 1.7 (NtSBT1.7) protein, thereby enhancing whitefly performance on tobacco plants. Further studies revealed that in wild-type plants, NtSBT1.7 could process tobacco preprohydroxyproline-rich systemin B (NtpreproHypSysB). After CLCuMuB infection, CLCuMuB βC1 could interfere with the processing of NtpreproHypSysB by NtSBT1.7, thereby impairing plant defenses against whitefly. These results contribute to our understanding of tripartite interactions among virus, plant, and whitefly, thus offering ecological insights into the spread of vector insect populations and the prevalence of viral diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Intestinal dysfunction plays a pivotal role in the development of acute pancreatitis (AP), however, the underlying mechanisms of intestinal dysfunction on severity of hyperlipidemic acute pancreatitis (HLAP) are still unclear. Herein, we explored the role of intestinal function on the severity of HLAP. We found that HLAP patients exhibit higher lipid and inflammatory response than AP patients. Hyperlipidemia significantly elevates serum lipids and worsen pancreatic damage in AP mice. In addition, significant exacerbated intestinal barrier damage and inflammation were observed in experimental HLAP mice, as evidenced by increased serum amylase and lipase levels, and pancreatic edema. Further, RNA-Seq showed that a markedly decrease of glutathione S-transferase pi (GSTpi) in colonic tissue of HLAP mice compared with AP mice, accompanied with increased serum lipopolysaccharides level. However, colonic GSTpi overexpression by adeno-associated virus significantly attenuated intestinal damage and subsequent pancreatic inflammation in HLAP mice. Mechanistically, GSTpi mitigated HLAP-mediated colonic NLRP3 inflammasome activation and barrier dysfunction. These results suggest that intestinal GSTpi deficiency exacerbates the severity of experimental HLAP, providing new insights for the clinical treatment of HLAP., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Disturbances in intestinal immune homeostasis predispose susceptible individuals to type 1 diabetes (T1D). G-protein-coupled receptor 41 (GPR41) is a receptor for short-chain fatty acids (SCFAs) mainly produced by gut microbiota, which plays key roles in maintaining intestinal homeostasis. In this study, we investigated the role of GPR41 in the progression of T1D. In non-obese diabetic (NOD) mice, we found that aberrant reduction of GPR41 expression in the pancreas and colons was associated with the development of T1D. GPR41-deficient (Gpr41 -/- ) mice displayed significantly exacerbated streptozotocin (STZ)-induced T1D compared to wild-type mice. Furthermore, Gpr41 -/- mice showed enhanced gut immune dysregulation and increased migration of gut-primed IFN-γ + T cells to the pancreas. In bone marrow-derived dendritic cells from Gpr41 -/- mice, the expression of suppressor of cytokine signaling 3 (SOCS) was significantly inhibited, while the phosphorylation of STAT3 was significantly increased, thus promoting dendritic cell (DC) maturation. Furthermore, adoptive transfer of bone marrow-derived dendritic cells (BMDC) from Gpr41 -/- mice accelerated T1D in irradiated NOD mice. We conclude that GPR41 is essential for maintaining intestinal and pancreatic immune homeostasis and acts as a negative regulator of DC maturation in T1D. GPR41 may be a potential therapeutic target for T1D., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation., Purpose: The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation., Methods: The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo, TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay., Results: Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation., Conclusion: Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB/p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo, suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024. Published by Elsevier GmbH.)

Background: The exploration of personality traits in relation to psychological constructs has become increasingly relevant in understanding the mental health of university students (the emerging adulthood). Studies have focused on how dimensions intersect with various psychological parameters., Aim: The study aims to identify distinct personality profiles among university students based on Eysenck's personality dimensions and investigate how these profiles differ across psychological constructs., Method: A quantitative methodology was utilized, involving 708 university students from Wenzhou and Nanjing in China as participants. The research employed the Eysenck Personality Questionnaire along with other psychological measures. Latent Profile Analysis was applied to categorize the participants into distinct personality profiles., Results: Four distinct personality profiles emerged: 'The Reserved Analyst,' 'The Social Diplomat,' 'The Unconventional Pragmatist,' and 'The Impulsive Truth-Teller.' Significant differences were found among these profiles on various psychological constructs. 'The Social Diplomat' exhibited the most adaptive psychological profile, with higher cognitive reappraisal ( F  = 45.818, p  < 0.001, η 2  = 0.163), meaning in life ( F   = 17.764, p < 0.001, η 2  = 0.070), and positive coping ( F  = 40.765, p < 0.001, η 2  = 0.148) compared to other profiles. Conversely, 'The Reserved Analyst' showed higher intolerance of uncertainty ( F  = 13.854, p   < 0.001, η 2  = 0.056) and state anxiety ( F  = 26.279, p   < 0.001, η 2  = 0.101)., Conclusion: This study enriches the understanding of personality traits in relation to psychological constructs within the context of university student populations. By identifying distinct personality profiles, it lays the groundwork for developing tailored mental health strategies that cater to the specific needs of different student groups., 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 © 2024 Pan, Zhou, Chen, Ke, Huang, Wu and Yan.)

Antibiotics are widely utilized in agriculture for the prevention and treatment of animal diseases. How-ever, the abuse and overuse of antibiotics progressively increase the risks of antibiotic residues and antibiotic resis-tance. The bioaccumulation and biomagnification of antibiotics through food chains will negatively affect ecological safety, and finally threaten human health. There are many shortages of traditional antibiotic detection techniques, such as complex procedures, complicated operation and time consuming, and thus are difficult to meet the demand of instant, efficient and accurate on-site detection. Therefore, it is crucial to develop rapid detection techniques of antibiotics to manage the application of antibiotics in agriculture. We reviewed the utilization, and management of antibiotics in animal husbandry, residual characteristics, and potential hazards of antibiotics in agricultural products, summarized the advancements in rapid detection techniques of antibiotics in agricultural products over the past five years, compared the advantages and disadvantages of different rapid detection techniques, and prospected the future development in this area. This review would provide a valuable reference to the control and point-of-care test of antibiotics in agricultural products.

Background: Electrical impedance tomography (EIT) is a relatively recent functional imaging technique that is both noninvasive and radiation free. EIT measures the associated voltage when a weak current is applied to the surface of the human body to determine the distribution of electrical resistance within tissues. We performed a bibliometrics-based review to explore the geographic hotspots of current research and future trends developing in the field of EIT for mechanical ventilation., Methods: The Web of Science database was searched from its inception to June 25, 2023. CiteSpace software was used to visualize and analyze the relevant literature and identify the most impactful literature, trends, and hotspots., Results: 363 articles describing EIT use in mechanical ventilation were identified. A fluctuating growth in the number of publications was observed from 1998 to 2023. Germany had the highest number of articles (n=154), followed by Italy (n=53) and China (n=52). A cluster analysis of keyword co-occurrence revealed that "titration", "ventilator-related lung injury", and "oxygenation" were the most actively researched terms associated with the use of EIT in mechanically ventilated patients., Conclusions: Significant progress has been made in EIT research for mechanical ventilation. EIT research is limited to a small number of countries with a present research focus on the prevention and treatment of ventilator-related lung injury, oxygenation status, and prone ventilation. These topics are expected to remain research hotspots in the future., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-98/coif). A.D. receives grants or contracts from NIH, CDC. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Deep convection in the Asian summer monsoon is a significant transport process for lifting pollutants from the planetary boundary layer to the tropopause level. This process enables efficient injection into the stratosphere of reactive species such as chlorinated very-short-lived substances (Cl-VSLSs) that deplete ozone. Past studies of convective transport associated with the Asian summer monsoon have focused mostly on the south Asian summer monsoon. Airborne observations reported in this work identify the East Asian summer monsoon convection as an effective transport pathway that carried record-breaking levels of ozone-depleting Cl-VSLSs (mean organic chlorine from these VSLSs ~500 ppt) to the base of the stratosphere. These unique observations show total organic chlorine from VSLSs in the lower stratosphere over the Asian monsoon tropopause to be more than twice that previously reported over the tropical tropopause. Considering the recently observed increase in Cl-VSLS emissions and the ongoing strengthening of the East Asian summer monsoon under global warming, our results highlight that a reevaluation of the contribution of Cl-VSLS injection via the Asian monsoon to the total stratospheric chlorine budget is warranted., Competing Interests: Competing interests statement:The authors declare no competing interest.

We conducted this study aimed to examine the impact of evidence-based nursing interventions on postoperative wound pain and complications after surgery for finger tendon injury. A total of 86 patients treated for finger tendon injuries at our hospital from January 2021 to October 2023 were selected and randomly divided into an experimental group and a control group. The control group received conventional nursing care, while the experimental group received evidence-based nursing interventions. The study compared the postoperative wound pain intensity, incidence of complications and patient satisfaction with nursing care between the two groups. The analysis revealed that compared with conventional care, evidence-based nursing interventions significantly reduced the level of wound pain (p = 0.034) and the incidence of complications (4.65% vs. 18.60%, p = 0.043). It also increased patient satisfaction with the nursing care (97.67% vs. 83.72%, p = 0.026). The study indicates that the application of evidence-based nursing interventions for patients with finger tendon injuries can reduce postoperative wound pain, decrease the incidence of complications and enhance patient satisfaction with nursing care., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

In precision medicine and clinical pain management, the creation of quantitative, objective indicators to assess somatosensory sensitivity was essential. This study proposed a fusion approach for decoding human somatosensory sensitivity, which combined multimodal (quantitative sensory test and neurophysiology) features to classify the dataset on individual somatosensory sensitivity and reveal distinct types of brain activation patterns. Sixty healthy participants took part in the experiment on somatosensory sensitivity that implemented cold, heat, mechanical punctate, and pressure stimuli, and the resting-state electroencephalography (EEG) was collected using BrainVision. The quantitative sensory testing (QST) scores of the participants were clustered using the unsupervised k-means algorithm into four subgroups: generally hypersensitive (HS), generally non-sensitive (NS), predominantly thermally sensitive (TS), and predominantly mechanically sensitive (MS). Furthermore, two types of power spectral density (PSD), band-based PSD (BB-PSD) and frequency-based PSD (FB-PSD), and two types of inter-electrode connectivity (IEC), band-based connectivity (BBC) and frequency-based connectivity (FBC), derived from resting-state EEG were subjected to feature selection with a proposed prior-compared minimum-redundancy maximum-relevance (PCMRMR) protocol. Their effectiveness was then tested by the supervised classification tasks using support vector machine (SVM), k-nearest neighbor (kNN), random forest (RF), and Gaussian classifier (GC). Brain networks of four somatosensory types were revealed by decoding fused multimodal data, namely type-averaged connectivity. The data from sixty healthy individuals were divided into training (n =59) and validation (n =1) datasets according to leave-one-subject-out (LOSO) criteria. The FBC was identified, which can serve as better brain signatures than BB-PSD, FB-PSD, and BBC to classify subjects as HS, NS, TS, or MS groups. Using the SVM, kNN, RF, and GC models, the best accuracy of 87% was obtained when classifying participants into HS, NS, TS, or MS groups. Moreover, the brain networks were decoded from HS, NS, TS, and MS groups by decoding the type-averaged connectivity fused from somatosensory phenotypes and selected FBC. It indicated that quantified multi-parameter somatosensory sensitivity could be achieved with acceptable accuracy, leading to considerable possibilities for using objective pain perception evaluation in clinical practice.

Type 1 diabetes (T1D) is an autoimmune disorder characterized by the destruction of insulin-producing pancreatic β cell. It contributes to high mortality, frequent diabetic complications, poor quality of life in patients and also puts a significant economic burden on health care systems. Therefore, the development of new therapeutic strategies is urgently needed. Recently, certain dietary compounds with potential applications in food industry, particularly polyphenols and polysaccharides, have gained increasing attention with their prominent anti-diabetic effects on T1D by modulating β cell function, the gut microbiota and/or the immune system. In this review, we critically discuss the recent findings of several dietary polyphenols and polysaccharides with the potential to protect against T1D and the underlying anti-diabetic mechanisms. More importantly, we highlight the current trends, major issues, and future directions of industrial production of polyphenols- and polysaccharides-based functional foods for preventing or delaying T1D.

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G + ) or Gram-negative bacteria (G - ) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G + bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G + bacteria. Additionally, depletion of SCFAs-producing G + bacteria rather than G - bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G + bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G + SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP., Competing Interests: The authors declare no conflicts of interest., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Aims: Accumulating evidence supports the indispensable role of protein arginine methyltransferase 5 (PRMT5) in the pathological progression of several human cancers. As an important enzyme-regulating protein methylation, how PRMT5 participates in vascular remodelling remains unknown. The aim of this study was to investigate the role and underlying mechanism of PRMT5 in neointimal formation and to evaluate its potential as an effective therapeutic target for the condition., Methods and Results: Aberrant PRMT5 overexpression was positively correlated with clinical carotid arterial stenosis. Vascular smooth muscle cell (SMC)-specific PRMT5 knockout inhibited intimal hyperplasia with an enhanced expression of contractile markers in mice. Conversely, PRMT5 overexpression inhibited SMC contractile markers and promoted intimal hyperplasia. Furthermore, we showed that PRMT5 promoted SMC phenotypic switching by stabilizing Kruppel-like factor 4 (KLF4). Mechanistically, PRMT5-mediated KLF4 methylation inhibited ubiquitin-dependent proteolysis of KLF4, leading to a disruption of myocardin (MYOCD)-serum response factor (SRF) interaction and MYOCD-SRF-mediated the transcription of SMC contractile markers., Conclusion: Our data demonstrated that PRMT5 critically mediated vascular remodelling by promoting KLF4-mediated SMC phenotypic conversion and consequently the progression of intimal hyperplasia. Therefore, PRMT5 may represent a potential therapeutic target for intimal hyperplasia-associated vascular diseases., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Plants face constant threats from insect herbivores, which limit plant distribution and abundance in nature and crop productivity in agricultural ecosystems. In recent decades, the whitefly Bemisia tabaci , a group of phloem-feeding insects, has emerged as pests of global significance. In this article, we summarize current knowledge on plant defenses against whitefly and approaches to engineer plant resistance to whitefly. Physically, plants deploy trichome and acylsugar-based strategies to restrain nutrient extraction by whitefly. Chemically, toxic secondary metabolites such as terpenoids confer resistance against whitefly in plants. Moreover, the jasmonate (JA) signaling pathway seems to be the major regulator of whitefly resistance in many plants. We next review advances in interfering with whitefly-plant interface by engineering of plant resistance using conventional and biotechnology-based breeding. These breeding programs have yielded many plant lines with high resistance against whitefly, which hold promises for whitefly control in the field. Finally, we conclude with an outlook on several issues of particular relevance to the nature and engineering of plant resistance against whitefly., 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 © 2023 Li, Li, Zhang, Wu, Zhao, Liu and Pan.)

The genomic components of multipartite viruses are encapsidated in separate virus particles, and the frequencies of genomic components represent one of the key genetic features. Many begomoviruses of economic significance are bipartite, and the details of the association between their genomic components remain largely unexplored. We first analyzed the temporal dynamics of the quantities of DNA-A and DNA-B and the B/A ratio of the squash leaf curl China virus (SLCCNV) in plants and found that while the quantities of DNA-A and DNA-B varied significantly during infection, the B/A ratio remained constant. We then found that changes in the B/A ratio in agrobacteria inoculum may significantly alter the B/A ratio in plants at 6 days post inoculation, but the differences disappeared shortly thereafter. We next showed that while the quantities of DNA-A and DNA-B among plants infected by agrobacteria, sap transmission and whitefly-mediated transmission differed significantly, the B/A ratios were similar. Further analysis of gene expression revealed that the ratio of the expression of genes encoded by DNA-A and DNA-B varied significantly during infection. Finally, we monitored the temporal dynamics of the quantities of DNA-A and DNA-B and the B/A ratio of another bipartite begomovirus, and a constant B/A ratio was similarly observed. Our findings highlight the maintenance of a constant ratio between the two genomic components of bipartite begomoviruses during infection and transmission, and provide new insights into the biology of begomoviruses., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Recombination is common in plant viruses such as geminiviruses, but the ecological and pathogenic consequences have been explored only in a few cases. Here, we found that a new begomovirus, tomato yellow leaf curl Shuangbai virus (TYLCSbV), probably originated from the recombination of Ageratum yellow vein China virus (AYVCNV) and tobacco curl shoot virus (TbCSV). Agrobacterium-mediated inoculation showed that TYLCSbV and AYVCNV have similar levels of infectivity on tomato and tobacco plants. However, the two viruses exhibit contrasting specificities for vector transmission, that is, TYLCSbV was efficiently transmitted by the whitefly Bemisia tabaci Mediterranean (MED) rather than by the whitefly B. tabaci Middle East-Asia Minor 1 (MEAM1), whereas AYVCNV was more efficiently transmitted by MEAM1. We also showed that the transmission efficiencies of TYLCSbV and AYVCNV are positively correlated with the accumulation of the viruses in whitefly whole bodies and organs/tissues. The key coat protein amino acids that determine their accumulation are between positions 147 and 256. Moreover, field surveys suggest that MED has displaced MEAM1 in some regions where TYLCSbV was collected. Viral competition assays indicated that TYLCSbV outcompeted AYVCNV when transmitted by MED, while the outcome was the opposite when transmitted by MEAM1. Our findings suggest that recombination has resulted in a shift of vector specificity that could provide TYLCSbV with a potential selective transmission advantage, and the population shift of whitefly cryptic species could have influenced virus evolution towards an extended trajectory of transmission., (© 2023 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Background: Acute pancreatitis (AP) is a recurrent inflammatory disease. Studies have shown that intestinal homeostasis is essential for the treatment of AP. Formononetin is a plant-derived isoflavone with antioxidant properties that can effectively treat a variety of inflammatory diseases. This study aims to investigate the role of formononetin in protecting against AP and underlying mechanism., Methods: Caerulein was used to induce AP. The inflammatory cytokines were detected using Quantitative real-time PCR and commercial kits. Histological examination was applied with hematoxylin and eosin staining. Western blot was conducted to detect expression of intestinal barrier protein and signaling molecular. Molecular docking was performed to assess protein-ligand interaction., Results: In this study, we found formononetin administration significantly reduced pancreatic edema, the activities of serum amylase, lipase, myeloperoxidase, and serum endotoxin. The mRNA levels of inflammatory cytokines such as tumor necrosis factor α, monocyte chemoattractant protein-1, interleukin-6, and interleukin-1 beta (IL-1β) in pancreas were also significantly decreased by formononetin. The following data showed formononetin pretreatment up-regulated the expressions of tight junction proteins in the colon, and decreased Escherichia coli translocation in the pancreas. In addition, formononetin inhibited the activation of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing 3 in pancreatic and colonic tissues of AP mice. Moreover, formononetin activated Kelch Like ECH Associated Protein 1 (Keap1) / Nuclear factor erythroid2-related factor 2 (Nrf2) signaling pathway to reduce reactive oxygen species (ROS) levels. Docking results showed that formononetin interact with Keap1 through hydrogen bond., Conclusions: These findings demonstrate that formononetin administration significantly mitigate AP through reducing oxidative stress and restoring intestinal homeostasis, and provide insights into the new treatment for AP., (© 2023. The Author(s).)

Objectives: This study investigated brain morphometry changes associated with fatigue severity in fibromyalgia (FM)., Methods: Clinical profiles and brain-MRI data were collected in patients with FM. Patients were divided into three groups based on their fatigue severity. Using voxel-based morphometry analysis and trend analysis, neural substrates showing volumetric changes associated with fatigue severity across the three groups were identified. Their seed-to-voxel structural covariance (SC) networks with the whole brain were studied in distribution and strength., Results: Among the 138 enrolled patients with FM, 23, 57, and 58 were categorised into the mild, moderate, and severe fatigue groups, respectively. The number of musculoskeletal pain regions and intensity of pain were not associated with fatigue severity, but somatic symptoms and psychiatric distress, including waking unrefreshed, depression, and anxiety, were associated with fatigue severity. After adjusting for anxiety and depression, decreased bilateral thalamic volumes were associated with higher fatigue severity. The SC distributions of the thalamic seed were more widespread to the frontal, parietal, subcortical, and limbic regions in patients with higher fatigue severity. In addition, increased right inferior temporal cortex volumes were associated with higher fatigue severity. The SC distributions of the right inferior temporal seed were more over the temporal cortex and the SC strengths of the seed were higher with the bilateral occipital cortex in patients with higher fatigue severity., Conclusions: The thalamus and the right inferior temporal cortex are implicated in the manifestation of fatigue severity in FM. Future therapeutic strategies targeting these regions are worthy of investigation.

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease with mysterious pathogenesis and limited effective therapies. G protein-coupled receptors (GPRs) participate in a variety of physiologic functions, and several GPRs have critical fibrosis-promoting or -inhibiting roles in pulmonary fibrosis. Here, we explored the role of GPR41 in the pathobiology of pulmonary fibrosis. We found that GPR41 expression was elevated in lung tissues of mice with bleomycin-induced pulmonary fibrosis and lung fibroblasts treated with transforming growth factor-β1 (TGF-β1). Knockout of GPR41 attenuated pulmonary fibrosis in mice, as evidenced by improved lung morphology, decreased lung weight and collagen secretion, and down-regulated α-SMA, collagen type I alpha and fibronectin expression in lungs. Additionally, GPR41 knockout inhibited the differentiation of fibroblasts to myofibroblasts, and decreased myofibroblast migration. By further mechanistic analysis, we demonstrated that GPR41 regulated TGF-β1-induced fibroblast-to-myofibroblast differentiation and Smad2/3 and ERK1/2 phosphorylation via its Gα i/o subunit but not Gβγ subunit. Together, our data indicate that GPR41 is involved in pulmonary fibroblast activation and fibrosis, and GPR41 represents a potential therapeutic target for pulmonary fibrosis., Competing Interests: Declaration of Interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Immunotherapy is an option for the treatment of advanced biliary tract cancer (BTC), although it has a low response rate. In this post hoc analysis, we investigated the predictive value of an immuno-genomic-radiomics (IGR) analysis for patients with BTC treated with camrelizumab plus gemcitabine and oxaliplatin (GEMOX) therapy., Methods: Thirty-two patients with BTC treated with camrelizumab plus GEMOX were prospectively enrolled. The relationship between high-throughput computed tomography (CT) radiomics features with immuno-genomic expression was tested and scaled with a full correlation matrix analysis. Odds ratio (OR) of IGR expression for objective response to camrelizumab plus GEMOX was tested with logistic regression analysis. Association of IGR expression with progression-free survival (PFS) and overall survival (OS) was analysed with a Cox proportional hazard regression., Results: CT radiomics correlated with CD8 + T cells ( r  = -0.72-0.71, p  = 0.004-0.047), tumour mutation burden (TMB) ( r  = 0.59, p  = 0.039), and ARID1A mutation ( r  = -0.58-0.57, p  = 0.020-0.034). There was no significant correlation between radiomics and programmed cell death protein ligand 1 expression ( p >0.96). Among all IGR biomarkers, only four radiomics features were independent predictors of objective response (OR = 0.09-3.81; p  = 0.011-0.044). Combining independent radiomics features into an objective response prediction model achieved an area under the curve of 0.869. In a Cox analysis, radiomics signature [hazard ratio (HR) = 6.90, p <0.001], ARID1A (HR = 3.31, p  = 0.013), and blood TMB (HR = 1.13, p  = 0.023) were independent predictors of PFS. Radiomics signature (HR = 6.58, p <0.001) and CD8 + T cells (HR = 0.22, p  = 0.004) were independent predictors of OS. Prognostic models integrating these features achieved concordance indexes of 0.677 and 0.681 for PFS and OS, respectively., Conclusions: Radiomics could act as a non-invasive immuno-genomic surrogate of BTC, which could further aid in response prediction for patients with BTC treated with immunotherapy. However, multicenter and larger sample studies are required to validate these results., Impact and Implications: Immunotherapy is an alternative for the treatment of advanced BTC, whereas tumour response is heterogeneous. In a post hoc analysis of the single-arm phase II clinical trial (NCT03486678), we found that CT radiomics features were associated with the tumour microenvironment and that IGR expression was a promising marker for tumour response and long-term survival., Clinical Trial Number: Post hoc analysis of NCT03486678., (© 2023 The Authors.)

The begomovirus-betasatellite complex constantly threatens crops in Asia. However, the quantitative relationship between begomoviruses and betasatellites remains largely unknown. The quantities of tobacco curly shoot virus (TbCSV) and its betasatellite (TbCSB) and their ratio varied significantly in initial infection, and thereafter, the ratio tended to become constant. The TbCSB/TbCSV ratio in agrobacteria inoculum significantly affected that in plants in the initial infection but not thereafter. Null-mutation of βC1 that encodes a multifunctional protein important for pathogenesis in TbCSB significantly reduced the TbCSB/TbCSV ratio in plants. Viral inoculum plants with higher TbCSB/TbCSV ratios promoted whitefly transmission of the virus. The expression of AV1 encoded by TbCSV, βC1 encoded by TbCSB and the βC1 / AV1 ratio varied significantly in the initial infection and thereafter the ratio tended to become constant. Additionally, the temporal dynamics of the ratio between another begomovirus and its betasatellite was similar to that of TbCSV and was positively regulated by βC1 . These results indicate that the ratio between monopartite begomoviruses and betasatellites tend to become constant as infection progresses, and is modulated by βC1 , but a higher betasatellite/begomovirus ratio in virally inoculated plants promotes virus transmission by whiteflies. Our findings provide novel insights into the association between begomoviruses and betasatellites.

Antimicrobial peptides (AMPs) play essential roles in maintaining intestinal health and have been suggested as possible therapeutic strategies against inflammatory bowel disease (IBD). However, the instability of AMPs in the process of transmission in vivo limits their application in the treatment of IBD. In this study, we constructed the mBD14-producing Lactococcus lactis NZ9000 ( L. lactis /mBD14) to achieve enteric delivery of mBD14 and evaluated its protective effect on dextran sodium sulfate (DSS)-induced colitis. Mice treated with L. lactis /mBD14 exhibited milder symptoms of colitis ( P < 0.01). Additionally, L. lactis /mBD14 treatment reversed DSS-induced epithelial dysfunction and reduced the production of pro-inflammatory cytokines in colon ( P < 0.01). Mechanistically, L. lactis /mBD14 significantly inhibited NOD-like receptor pyrin domain containing three inflammasome-mediated pro-inflammatory response ( P < 0.05) and regulated microbiota homeostasis by promoting the abundance of probiotic bacteria Akkermansia muciniphila and Faecalibacterium prausnitzii and decreasing the pathogenic Escherichia coli ( P < 0.01). Taken together, this study demonstrates the protective effect of L. lactis /mBD14 in DSS-induced colitis, and suggests that oral administration of L. lactis /mBD14 may represent a potential therapeutic strategy for IBD.

Long-term treatment with adriamycin (ADR) is associated with higher incidences of cumulative cardiotoxicity manifest as heart failure. ADR-induced cardiomyopathy is characterized by extensive fibrosis that is caused by cardiac fibroblast activation. To date, however, no specific treatment is available to alleviate ADR-induced cardiotoxicity. Protein arginine methyltransferase 5 (PRMT5), a major enzyme responsible for methylation of arginine, regulates numerous cellular processes such as cell differentiation. In the present study we investigated the role of PRMT5 in cardiac fibrosis. Mice were administered ADR (3 mg/kg, i.p., every 2 days) for 2 weeks. We showed that aberrant PRMT5 expression was largely co-localized with α-SMA-positive activated cardiac fibroblasts in ADR-injected mice and in ADR-treated cardiac fibroblasts in vitro. PRMT5-overexpression exacerbated, whereas PRMT5 knockdown alleviated ADR-induced cardiac fibrosis in vivo and TGF-β1-induced cardiac fibroblast activation in vitro. We demonstrated that PRMT5-overexpression enhanced methylated-Smad3 levels in vivo and in vitro. Pretreatment with a specific PRMT5 inhibitor EPZ015666 (5 nM) or overexpression of a catalytically inactive mutant of PRMT5, PRMT5(E444Q), reduced PRMT5-induced methylation of Smad3, thus suppressing PRMT5-mediated cardiac fibroblast activation in vitro. Furthermore, ADR activated cardiac fibroblasts was depending on autocrine TGF-β1. Taken together, our results demonstrate that PRMT5 promotes ADR-induced cardiac fibrosis via activating cardiac fibroblasts, suggesting that it may be a potential therapeutic target of ADR-caused cardiotoxicity., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Acute pancreatitis (AP) is an acute inflammatory abdominal disease frequently associated with intestinal barrier dysfunction. Biochanin A (BCA), a dietary isoflavone, has gained increasing interest with its pronounced biological activities. However, its potential beneficial effects on AP have not been demonstrated. Herein, we explored the protective effect of BCA on caerulein-induced AP in BALB/c mice and underlying mechanisms. BCA alleviated AP as evidenced by reduced serum amylase and lipase levels, pancreatic edema, pancreatic myeloperoxidase activity, and improved pancreatic morphology. Amelioration of pancreatic damage by BCA was associated with reduced levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and monocyte chemotactic protein-1 in both pancreas and colon. Moreover, BCA attenuated AP-associated barrier damage by upregulating the expression of tight junction proteins zonulin occluding (ZO)-1, ZO-2, occludin, and claudin-1. Concomitantly, the translocation of pathogenic bacteria Escherichia coli (E. coli) to pancreas was reduced by BCA. More importantly, reduction of E. coli dissemination by BCA inhibited the TLR4-MAPK/NF-κB signaling and NLRP3 inflammasome activation, thereby protecting against AP and related intestinal injury. Consistently, TLR4 inhibition by TAK-242 pre-treatment counteracted the anti-inflammatory effects of BCA in acinar cells. Taken together, our study extends beneficial effects of BCA to AP prevention, and dietary BCA supplement may be a potential strategy to safeguard AP., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hupelactones A ( 1 ) and B ( 2 ), two new eudesmanolide-type enantiomers of the corresponding compounds, along with four mono- ( 3 - 6 ) and nine dimeric- ( 7 - 15 ) known sesquiterpenoids were isolated from the whole plant of Chloranthus henryi var. hupehensis (syn. C. henryi) . The new structures including the absolute configurations were determined by comparison with previously reported enantiomers, extensive spectroscopic methods in combination with electronic circular dichroism (ECD) calculations. All the isolates were evaluated for their inhibitory activities against the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine BV-2 microglial cells. Among them, the dimeric lindenane sesquiterpenoids shizukaols F ( 8 ) and G ( 11 ) exhibited the most potent activities, with IC 50 values of 2.65 and 4.60 μM, respectively.

Objective: To investigate the effect of individualized positive end expiratory pressure (PEEP) setting guided by chest electrical impedance tomography (EIT) on the incidence of hypoxemia in elderly patients undergoing robot-assisted radical prostatectomy in the post anesthesia care unit (PACU). Methods: From September 2020 to October 2021, sixty elderly patients, with the American Association of Anesthesiologists (ASA) of Grade Ⅰ to Ⅲ, who underwent selective robot-assisted radical prostatectomy under general anesthesia in the Cancer Hospital Affiliated to Fudan University were selected. The participants were divided into two groups by the minimum randomized grouping method: EIT-PEEP group (EP group, n =30) and fixed PEEP group (FP group, n =30). After completion of tracheal intubation and establishment of pneumoperitoneum flexion posture, the individualized PEEP setting was guided by EIT in EP group, and the PEEP setting in FP group was 5 cmH 2 O (1 cmH 2 O=0.098 kPa) to the end of operation. During the operation, the ventilation mode of pressure regulation volume control was adopted. The driving pressure, dynamic lung compliance (Cdyn), oxygenation index and hemodynamics were recorded at 5 min (T 1 ), 30 min (T 2 ), 60 min (T 3 ) after PEEP setting and at the time of tracheal catheter removal (T 4 ) in both groups. The primary end point was the incidence of hypoxemia in PACU after extubation. Results: The incidence of hypoxemia after extubation was 3.3% (1/30) in EP group and 26.7% (8/30) in FP group ( P =0.030). The difference of driving pressure between the two groups at T 2 [(13.1±2.4) cmH 2 O vs (14.9±2.9) cmH 2 O, P =0.012], T 3 [(12.7±2.4) cmH 2 O vs (15.6±2.8) cmH 2 O, P <0.001] was statistically significant. In EP group, Cdyn was improved at T 2 [(38.4±7.2) ml/cmH 2 O vs (31.9±5.2) ml/cmH 2 O, P =0.006] and T 3 [(37.5±9.0) ml/cmH 2 O vs (30.4±5.9) ml/cmH 2 O, P =0.001]. In EP group, PaO 2 /FiO 2 increased at T 1 [(465.7±84.5) mmHg vs (383.5±58.0) mmHg, 1 mmHg=0.133 kPa, P <0.001], T 2 [(504.7±105.8) mmHg vs (418.9±73.7) mmHg, P =0.001], T 3 [(520.7±92.2) mmHg vs (423.2±90.7) mmHg, P <0.001], T 4 [(368.7±42.0) mmHg vs (339.5±54.9) mmHg, P =0.024]. Conclusion: The individualized PEEP setting guided by EIT can reduce the incidence of hypoxemia in elderly patients undergoing robot assisted radical prostatectomy in PACU.

Whiteflies of the Bemisia tabaci complex transmit hundreds of plant viruses belonging to the genera Begomovirus and Crinivirus , among others. Tripartite interactions of whitefly-virus-plant frequently occur during virus infection and transmission. Specifically, virus transmission-related behavior of whitefly, such as preference and feeding, may be altered by viruses and thus exert significant impacts on the outcome of virus spread and epidemics. Here, we provide an overview on the current understanding of the manipulation of whitefly behavior by plant viruses. Plant viruses can significantly modulate whitefly preference and feeding behavior, either directly or in a plant-mediated manner. In general, non-viruliferous whiteflies tend to prefer virus-infected plants, and viruliferous whiteflies are more likely to prefer uninfected plants. In most cases, virus infection of plants and/or whitefly seems to exhibit positive or no effects on whitefly feeding on plants. The significance and evolution of these patterns are then discussed. Finally, we suggest several future directions of research, such as the exploration of temporal dynamics and the dissection of underlying mechanisms of virus-induced changes in whitefly behavior.

Scope: Dietary fibers can alter gut microbiota and microbial metabolite profiles. SCFAs are produced by bacterial fermentation of fiber, mediating immune homeostasis through G-protein-coupled receptors (GPCRs). GPR109a, a receptor for niacin and butyrate, expressed by immune cells and non-immune cells, is a key factor regulating immune responses. However, the role and underlying mechanisms of GPR109a in type 1 diabetes (T1D) remain unclear., Methods and Results: Experimental T1D was induced by streptozotocin in GPR109a-deficient (Gpr109a -/- ) and wild type mice. The study found that Gpr109a -/- mice were more susceptible to T1D with dysregulated immune responses, along with increased M1 macrophage polarization (from 10.55% to 21.48%). Further, an adoptive transfer experiment demonstrated that GPR109a-deficient macrophages promoted the homing of intestine-derived type 1 cytotoxic T cells to pancreas (from 18.91% to 24.24%), thus disturbing the pancreatic immune homeostasis in non-obese diabetic mice. Mechanistically, GPR109a deficiency promoted M1 macrophage polarization associated with the activation of suppressor of cytokine signaling 3-signal transducer and activator of transcription 1 signaling pathway., Conclusion: The findings reveal that macrophage GPR109a deficiency accelerates the development of T1D. Activation of GPR109a on macrophage by dietary components may provide a new strategy for preventing or treating T1D., (© 2022 Wiley-VCH GmbH.)

To evaluate the safety of the 15-valent pneumococcal conjugate vaccine (PCV15 (by LvZhu & Co. Ltd)) in healthy infants aged 2 months (minimum to 6 weeks) and 3 months old. This phase I clinical trial enrolled 80 subjects in Laishui County, Hebei Province, China. The total population was divided into 4 age groups on average: 20 adults (≥18 years) and 20 children (1-5 years) all received one vaccine dose; 20 infants (3 months) received the vaccine according to a 3-dose schedule at 0, 1, and 2 months. Twenty infants (2 months, minimum of 6 weeks old) received the vaccine according to a 3-dose schedule of 0, 2, and 4 months. The adverse events (AEs) until 30 days after each dose and serious adverse events (SAEs) until 6 months after the whole dose were reported. The solicited and unsolicited AE frequencies and laboratory indices were similar among the treatment groups. No vaccine-related SAEs were reported. Most vaccine-related adverse events consisting of systemic and local reactions were fever and pain. One hypersensitivity manifested as systemic urticaria that occurred on the third day after the second dose in the 2-month group. The 15-valent pneumococcal conjugate vaccine was generally well tolerated in infants.

Viruses pose a great threat to animal and plant health worldwide, with many being dependent on insect vectors for transmission between hosts. While the virus-host arms race has been well established, how viruses and insect vectors adapt to each other remains poorly understood. Begomoviruses comprise the largest genus of plant-infecting DNA viruses and are exclusively transmitted by the whitefly Bemisia tabaci . Here, we show that the vector Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway plays an important role in mediating the adaptation between the begomovirus tomato yellow leaf curl virus (TYLCV) and whiteflies. We found that the JAK/STAT pathway in B. tabaci functions as an antiviral mechanism against TYLCV infection in whiteflies as evidenced by the increase in viral DNA and coat protein (CP) levels after inhibiting JAK/STAT signaling. Two STAT-activated effector genes, BtCD109-2 and BtCD109-3 , mediate this anti-TYLCV activity. To counteract this vector immunity, TYLCV has evolved strategies that impair the whitefly JAK/STAT pathway. Infection of TYLCV is associated with a reduction of JAK/STAT pathway activity in whiteflies. Moreover, TYLCV CP binds to STAT and blocks its nuclear translocation, thus, abrogating the STAT-dependent transactivation of target genes. We further show that inhibition of the whitefly JAK/STAT pathway facilitates TYLCV transmission but reduces whitefly survival and fecundity, indicating that this JAK/STAT-dependent TYLCV-whitefly interaction plays an important role in keeping a balance between whitefly fitness and TYLCV transmission. This study reveals a mechanism of plant virus-insect vector coadaptation in relation to vector survival and virus transmission.

Introduction: With rapid increase in the aging population, falls injuries have become an important public health problem. However, limited data have been reported on the associations between meteorological factors and falls injuries in the elderly. This study assessed the epidemiology of falls injuries and explored this association in the elderly in Guangzhou, China., Methods: Data on elderly falls injury cases and meteorological variables from 2014 to 2018 in Guangzhou were collected from the Guangzhou Injury Monitoring System and Guangzhou Meteorological Bureau, respectively. The monthly average data on falls injuries and meteorological factors were applied to the data analysis. These correlations were conducted using Pearson correlation analysis. A multiple linear regression model was used to estimate the effects of meteorological factors on falls injuries in the elderly in Guangzhou, China., Results: Accounting for 49.41% of causes of elderly injury were falls in the Guangzhou Injury Monitoring System from 2014 to 2018, which occupied first place for five consecutive years. The monthly number of elderly falls injury cases was lowest in April and highest in December, and had a positive correlation with monthly mean wind speed ( r = 0.187, P < 0.01) and a negative correlation with monthly atmospheric pressure ( r = -0.142, P < 0.05). A multiple linear regression model was constructed ( F = 10.176, P < 0.01), which explained 23.7% of the variances ( R 2 = 0.237). Monthly mean wind speed ( β = 76.85, P < 0.01) and monthly mean atmospheric pressure ( β = -3.162, P < 0.01) were independent factors affecting monthly elderly falls injuries., Conclusions: Falls are the primary cause of injury among elderly people in Guangzhou, China. Meteorological factors are related to falls injuries in the elderly population. Decreasing activity during high wind and low atmospheric pressure weather may help reduce the number of elderly falls injury cases., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Inflammatory bowel disease (IBD), comprised of ulcerative colitis and Crohn's disease, is a chronic relapsing inflammatory disease of the gastrointestinal tract that closely related to immune dysfunction. Macrophages are the key gatekeeper of intestinal immune homeostasis and have vital influence on IBD. Hence, macrophages have been recognized as attractive targets to develop new therapeutic approaches for the disease. Recently, the growing field of immunometabolism has reinforced that metabolism reprogramming is a key determinant that dictates macrophage functions and subsequent disease progression. Herein, we elaborated how metabolic alterations underlie intestinal macrophage phenotype and function during IBD, and how microenvironmental cues trigger their metabolic reprogramming processes. More importantly, we deciphered the distinguishing characteristic of macrophage immunometabolism in IBD from other inflammatory diseases, and also summarized potential therapeutic approaches for IBD by manipulating cellular metabolism of macrophages. Finally, we discussed the major opportunities and challenges of harnessing metabolism to modulate aberrant macrophage responses in IBD. Altogether, our overview provides a framework for understanding the critical roles and potential therapeutic targets of macrophage immunometabolism in IBD., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Both N6-methyladenosine (m6A) ribonucleic acid (RNA) methylation and ferroptosis regulators are demonstrated to have significant effects on the malignant clinicopathological characteristics of pancreatic adenocarcinoma (PAAD) patients. However, the currently available clinical indexes are not sufficient to predict precise prognostic outcomes pf PAAD patients accurately. This study aims to examine the clinicopathologic features of m6A RNA methylation and ferroptosis regulators in predicting the outcomes of different types of cancer., Methods: As the foundation for this research, the differentially expressed genes (DEGs) between PAAD tissues and adjacent normal tissues were first identified. Next, dimensional reduction analysis (DCA) based on m6A RNA methylation regulators and ferroptosis regulators were performed and DEGs between good/poor prognosis PAAD patient clusters were identified. DEGs were then screened by Cox analysis, and finally a risk signature was established by least absolute shrinkage and selection operator (LASSO) analyses. The prediction model based on risk score was further evaluated by a validation set from Gene Expression Omnibus (GEO) database., Results: In total, 4 m6A RNA methylation regulator genes and 29 ferroptosis regulator genes were found to have close causal relationships with the prognosis of PAAD, and a risk score with 3 m6A methylation regulators (i.e., IGF2BP2, IGF2BP3 , and METTL16 ) and 4 ferroptosis regulators (i.e., ENPP2 , ATP6V1G2 , ITGB4 , and PROM2 ) was constructed and showed to be highly involved in PAAD progression and could serve as effective markers for prognosis with AUC value equaled 0.753 in training set and 0.803 in validation set., Conclusions: The combined prediction model, composed of seven regulators of m6A methylation and ferroptosis, in this study more effectively reflects the progression and prognosis of PAAD than previous single genome or epigenetic analysis. Our study provides a broader perspective for the subsequent establishment of prognostic models and the patients may benefit from more precision management., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-941/coif). The authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Objective: To analyze the safety of an inactivated 2019-nCoV vaccine (Vero cell) in adults aged 60 years and older. Methods: A randomized, double-blind, placebo-controlled clinical study was conducted in May 2020 The eligible residents aged 60 and above were recruited in Renqiu city, Hebei Province. A total of 422 subjects (phase Ⅰ/Ⅱ:72/350) were enrolled. Two doses of the trial vaccine or placebo were randomly administered according to a 0 and 28-day immunization schedule. Subjects were randomly divided into two groups in Phase Ⅰ. Within each group, participants received vaccine or placebo in a ratio of 2∶1. Subjects were randomly divided into four groups in phase Ⅱ to receive low-dose, medium-dose, high-dose vaccine and placebo, respectively, in a ratio of 2∶2∶2∶1. A combination of regular follow-up and active reporting was used to observe adverse reactions within 28 days after vaccination, and compare the incidence rate of adverse reactions in the trial and control groups. Results: 422 subjects were (66.45±4.70) years old, and 48.82% were male (206/422). There were 100, 124, 124 and 74 patients enrolled into the low-dose, medium-dose, high-dose vaccine groups and the placebo group, respectively. One person without the vaccination was removed, and 421 participants who received at least one dose of vaccine were included in the safety analysis. Within 28 days after the first or second dose, a total of 20.67% (87/421) subjects had adverse reactions (both solicitation and non-solicitation). About 76 patients suffered grade 1 adverse reactions [18.05% (76/421)] and 22 patients suffered grade 2 adverse reactions [5.23% (22/421)]. No grade 3 or above adverse reactions occurred. A total of 19.71% (83/421) subjects had solicited adverse reactions. The most common grade 1 adverse reaction was injection site pain, followed by fever and fatigue. The most common grade 2 adverse reactions were fever and fatigue, followed by muscle pain and injection site redness. A total of 2.61% (11/421) subjects had unsolicited adverse reactions. A total of 1.66% (7/421) subjects had serious adverse events after vaccination, and no serious vaccine-related adverse events were reported. Conclusions: The inactivated SARS-CoV-2 vaccine is safe for people aged 60 years and above.

Although peripheral blood reticulocyte enumeration reflects bone marrow functional integrity, which is important for differential diagnosis of hematological diseases, the factors affecting its accuracy have not been adequately addressed. Using 100 consecutive venous blood samples being processed with four supravital staining techniques [i.e., brilliant cresyl blue (BCB), new methylene blue (NMB), and BCB/NMB with Liu’s stain] for reticulocyte enumeration, two technologists (senior vs. junior) conducted microscopic counting. The results were compared with those obtained with an automated system (Sysmex XE-5000) that served as the standard. The aims of this study were to identify (1) the technique that gave the most reliable outcome, and (2) possible human factors (i.e., seniority, repeated counting) that may affect the counting results. Analysis showed least bias (i.e., deviation from automated counting) associated with BCB staining, followed by NMB. In addition, the senior observer exhibited a higher bias in counting compared with their junior counterpart. Repeated counting also correlated with a higher rate of bias. Nevertheless, inter-observer consistency was high (intraclass correlation coefficient >0.95) and inter-/intra-observer variations were non-significant (both p > 0.05). Our results supported the use of BCB stain for reticulocyte enumeration and the reliability of manual counting despite the involvement of human factors, which had negligible impacts on the final outcomes.

Objective: This study aimed to conduct an in-depth investigation of the learning framework used for deriving diagnostic results of temporal bone diseases, including cholesteatoma and Langerhans cell histiocytosis (LCH). In addition, middle ear inflammation (MEI) was diagnosed by CT scanning of the temporal bone in pediatric patients., Design: A total of 119 patients were included in this retrospective study; among them, 40 patients had MEI, 38 patients had histology-proven cholesteatoma, and 41 patients had histology-proven LCH of the temporal bone. Each of the 119 patients was matched with one-third of the disease labels. The study included otologists and radiologists, and the reference criteria were histopathology results (70% of cases for training and 30% of cases for validation). A multilayer perceptron artificial neural network (VGG16&#95;BN) was employed and classified, based on radiometrics. This framework structure was compared and analyzed by clinical experts according to CT images and performance., Results: The deep learning framework results vs. a physician's diagnosis, respectively, in multiclassification tasks, were as follows. Receiver operating characteristic (ROC) (cholesteatoma): (0.98 vs. 0.91), LCH (0.99 vs. 0.98), and MEI (0.99 vs. 0.85). Accuracy (cholesteatoma): (0.99 vs. 0.89), LCH (0.99 vs. 0.97), and MEI (0.99 vs. 0.89). Sensitivity (cholesteatoma): (0.96 vs. 0.97), LCH (0.99 vs. 0.98), and MEI (1 vs. 0.69). Specificity (cholesteatoma): (1 vs. 0.89), LCH (0.99 vs. 0.97), and MEI (0.99 vs. 0.89)., Conclusion: This article presents a research and learning framework for the diagnosis of cholesteatoma, MEI, and temporal bone LCH in children, based on CT scans. The research framework performed better than the clinical experts., 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. The reviewer HJ declared a shared parent affiliation with the authors to the handling editor at the time of review., (Copyright © 2022 Duan, Pan, Chen, Qiao and Xu.)

The current study aims to evaluate the probiotic potential of lactic acid bacteria isolated from infant feces, and select candidates to be used as potential antioxidants for the treatment of oxidative stress-related diseases; To meet the criteria for probiotic attributes, the isolates were subjected to various in vitro tests and 16S rRNA genotypic characterization. Besides, anti-inflammatory and anti-oxidative effects of selected isolates were separately assessed by real-time quantitative PCR and Western blot; The selected strains belonged to Lactobacillus gasseri , Lactiplantibacillus plantarum and Lacticaseibacillus rhamnosus . Notably, three selected strains ( L. gasseri FWJL-4, L. plantarum Fjias-5 and L. rhamnosus FSJ-13) particularly L. gasseri FWJL-4 significantly down-regulated mRNA expression levels of tumor necrosis factor α (TNFα), Interleukin-6 (IL-6) and IL-1β. Most importantly, three strains-treated RAW 264.7 murine macrophages displayed enhanced activities of antioxidant enzymes and reduced H 2 O 2 production, which were associated with the enhanced expression levels of nuclear factor-erythroid 2 related factor 2 and heme oxygenase-1; Three selected strains, particularly L. gasseri FWJL-4, are good candidates that merit additional in vivo investigation for the validation and application of their health-promoting effects.