A c-di-GMP binding effector controls cell size in a cyanobacterium.

Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule. It is also a critical player in the regulation of cell size and cell behaviors such as cell aggregation and phototaxis in cyanobacteria, which constitute an important group of prokaryotes for their roles in the ecology and evolution of the Earth. However, c-di-GMP receptors have never been revealed in cyanobacteria. Here, we report the identification of a c-di-GMP receptor, CdgR, from the filamentous cyanobacterium Anabaena PCC 7120. Crystal structural analysis and genetic studies demonstrate that CdgR binds c-di-GMP at the dimer interface and this binding is required for the control of cell size in a c-di-GMP-dependent manner. Different functions of CdgR, in ligand binding and signal transmission, could be separated genetically, allowing us to dissect its molecular signaling functions. The presence of the apo-form of CdgR triggers cell size reduction, consistent with the similar effects observed with a decrease of c-di-GMP levels in cells. Furthermore, we found that CdgR exerts its function by interacting with a global transcription factor DevH, and this interaction was inhibited by c-di-GMP. The lethal effect triggered by conditional depletion of DevH or by the production of several point-mutant proteins of CdgR in cells indicates that this signaling pathway plays critical functions in Anabaena. Our studies revealed a mechanism of c-di-GMP signaling in the control of cell size, an important and complex trait for bacteria. CdgR is highly conserved in cyanobacteria, which will greatly expand our understanding of the roles of c-di-GMP signaling in these organisms.

CX3C chemokine: Hallmarks of fibrosis and ageing.

Fibrosis refers to the progressive tissue lesion process characterized by excessive secretion and deposition of extracellular matrix (ECM). Abnormal fibrous tissue deposition distorts tissue architecture and leads to the progressive loss of organ function. Notably, fibrosis is one of the primary pathological appearances of many end stage illnesses, and is considered as a lethal threat to human health, especially in the elderly with ageing-related diseases. CX3C ligand 1 (CX3CL1) is the only member of chemokine CX3C and binds specifically to CX3C receptor 1 (CX3CR1). Different from other chemokines, CX3CL1 possesses both chemotactic and adhesive activity. CX3CL1/CX3CR1 axis involves in various physiological and pathological processes, and exerts a critical role in cells from the immune system, vascular system, and nervous system etc. Notably, increasing evidence has demonstrated that CX3CL1/CX3CR1 signaling pathway is closely related to the pathological process of fibrosis in multiple tissue and organs. We reviewed the crucial role of CX3CL1/CX3CR1 axis in fibrosis and ageing and systematically summarized the underlying mechanism, which offers prospective strategies of targeting CX3C for the therapy of fibrosis and ageing-related diseases.

2,2'-Bisdinitromethyl-5,5'-bistetrazole: A High-Performance, Multi-Nitro Energetic Material with Excellent Oxygen Balance.

Bistetrazoles are highly sought after for developing innovative high-energy density materials. The 1,1'-substituted bistetrazoles, exemplified by TKX-50, have outstanding performance. However, the research of high-perfomance 2,2'-substituted bistetrazoles remains limited. In this work, dinitromethyl groups were introduced into bistetrazole structures as 2,2'-substituted bistetrazoles (BDBTZ), which was extensively characterized through NMR, thermal analysis, and single crystal X-ray diffraction, exhibiting excellent oxygen balance, moderate sensitivity, acceptable thermal stability, high crystal density, and excellent detonation performance.

DP7-C/mir-26a system promotes bone regeneration by remodeling the osteogenic immune microenvironment.

OBJECTIVE: This study investigates the DP7-C/miR-26a complex as a stable entity resulting from the combination of miR-26a with the immunomodulatory peptide DP7-C. Our focus is on utilizing DP7-C loaded with miR-26a to modulate the immune microenvironment in bone and facilitate osteogenesis. METHODS: The DP7-C/miR-26a complex was characterized through transmission electron microscopy, agarose electrophoresis, and nanoparticle size potentiometer analysis. Transfection efficiency and cytotoxicity of DP7-C were assessed using flow cytometry and the CCK-8 assay. We validated the effects of DP7-C/miR-26a on bone marrow mesenchymal stem cells (BMSCs) and macrophages RAW 264.7 through gene expression and protein synthesis assays. A comprehensive evaluation of appositional bone formation involved micro-CT imaging, histologic analysis, and immunohistochemical staining. RESULTS: DP7-C/miR-26a, a nanoscale, and low-toxic cationic complex, demonstrated the ability to enter BMSCs and RAW 264.7 via distinct pathways. The treatment with DP7-C/miR-26a significantly increased the synthesis of multiple osteogenesis-related factors in BMSCs, facilitating calcium nodule formation in vitro. Furthermore, DP7-C/miR-26a promoted M1 macrophage polarization toward M2 while suppressing the release of inflammatory factors. Coculture studies corroborated these findings, indicating significant repair of rat skull defects following treatment with DP7-C/miR-26a. CONCLUSION: The DP7-C/miR-26a system offers a safer, more efficient, and feasible technical means for treating bone defects.

Causal relationship between inflammatory skin diseases and breast cancer: A bidirectional Mendelian randomization study.

INTRODUCTION: Prior research has explored the relationship between inflammatory skin disorders and breast cancer (BC), yet the causality of this association remains uncertain. METHODS: Utilizing a bidirectional two-sample Mendelian randomization (MR) approach, this study aimed to elucidate the causal dynamics between various inflammatory skin conditions-namely acne, atopic dermatitis, psoriasis vulgaris, urticaria, and rosacea-and BC. Genetic variants implicated in these disorders were sourced from comprehensive genome-wide association studies representative of European ancestry. In the forward MR, BC was posited as the exposure, while the reverse MR treated each inflammatory skin disease as the exposure. A suite of analytical methodologies, including random effects inverse variance weighted (IVW), weighted median (WME), and MR-Egger, were employed to probe the causative links between inflammatory skin diseases and BC. Sensitivity analyses, alongside evaluations for heterogeneity and pleiotropy, were conducted to substantiate the findings. RESULTS: The MR analysis revealed an increased risk of acne associated with BC (IVW: OR = 1.063, 95% CI = 1.011-1.117, p = 0.016), while noting a decreased risk of atopic dermatitis (AD) in BC patients (IVW: OR = 0.941, 95% CI = 0.886-0.999, p = 0.047). No significant associations were observed between BC and psoriasis vulgaris, urticaria, or rosacea. Conversely, reverse MR analyses detected no effect of BC on the incidence of inflammatory skin diseases. The absence of pleiotropy and the consistency of these outcomes strengthen the study's conclusions. CONCLUSION: Findings indicate an elevated incidence of acne and a reduced incidence of AD in individuals with BC within the European population.

Efficacy of Internet-Based Cognitive Behavioral Therapy for Subthreshold Depression Among Older Adults in Institutional Long-Term Care Settings: Pragmatic Randomized Controlled Trial.

BACKGROUND: Subthreshold depression (sD) is prevalent in older populations in long-term care (LTC) settings, but psychological therapy in LTC settings in China is not readily available. Thus, internet-based cognitive behavioral therapy (ICBT) may be suitable for this population, but research on the efficacy of ICBT for older adults with sD, especially those living in LTC settings, is limited. OBJECTIVE: This study aimed to evaluate the efficacy and acceptability of ICBT treatment for sD among LTC residents in China. We also examined whether ICBT is as effective as group-based cognitive behavioral therapy (CBT) for treating sD in this population. METHODS: We conducted a pragmatic randomized controlled trial, which included 18 LTC institutions. A total of 354 participants were randomized to ICBT, group-based CBT, or a waiting list and were followed up for 12 months. The primary outcome was self-reported depressive symptoms on the Center for Epidemiological Studies Depression Scale (CES-D). Secondary outcomes were the scores of the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-Item (GAD-7), and Geriatric Depression Scale (GDS). A mixed-effects model was used to assess the efficacy of ICBT. RESULTS: The ICBT group showed a significant improvement in self-reported depressive symptoms, which was maintained at the 12-month follow-up (all P<.001). The ICBT group exhibited a significantly larger reduction in the scores of the CES-D (Cohen d=0.07, 95% CI 0.04-0.09; P=.01), PHQ-9 (d=0.30, 95% CI 0.28-0.33; P<.001), GDS (d=0.10, 95% CI 0.08-0.13; P<.001), and GAD-7 (d=0.19, 95% CI 0.17-0.22; P<.001) compared with a waiting list at postintervention. ICBT had significantly stronger effects than CBT on the PHQ-9 and GAD-7 at postintervention (d=0.15, 95% CI 0.13-0.17; P<.001 and d=0.21, 95% CI 0.19-0.23; P<.001, respectively), 6-month follow-up (d=0.18, 95% CI 0.16-0.21; P<.001 and d=0.18, 95% CI 0.15-0.21; P<.001, respectively), and 12-month follow-up (d=0.15, 95% CI 0.11-0.19; P<.001 and d=0.18, 95% CI 0.14-0.21; P<.001, respectively). CONCLUSIONS: ICBT is a relatively effective and acceptable intervention for reducing depressive symptoms among Chinese LTC residents with sD. These findings indicate the usefulness of ICBT application for sD in LTC settings. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030697; https://www.chictr.org.cn/showproj.aspx?proj=50781.

Genetic fingerprint construction and genetic diversity analysis of sweet potato (Ipomoea batatas) germplasm resources.

BACKGROUND: China is the largest producer of sweet potato in the world, accounting for 57.0% of the global output. Germplasm resources are the basis for promoting innovations in the seed industry and ensuring food security. Individual and accurate identification of sweet potato germplasm is an important part of conservation and efficient utilization. RESULTS: In this study, nine pairs of simple sequence repeat molecular markers and 16 morphological markers were used to construct genetic fingerprints for sweet potato individual identification. Combined with basic information, typical phenotypic photographs, genotype peak graphs, and a two-dimensional code for detection and identification were generated. Finally, a genetic fingerprint database containing 1021 sweet potato germplasm resources in the "National Germplasm Guangzhou Sweet Potato Nursery Genebank in China" was constructed. Genetic diversity analysis of the 1021 sweet potato genotypes using the nine pairs of simple sequence repeat markers revealed a narrow genetic variation range of Chinese native sweet potato germplasm resources, and Chinese germplasm was close to that from Japan and the United States, far from that from the Philippines and Thailand, and the furthest from that from Peru. Sweet potato germplasm resources from Peru had the richest genetic diversity, supporting the view that Peru is the center of origin and domestication of sweet potato varieties. CONCLUSIONS: Overall, this study provides scientific guidance for the conservation, identification, and utilization of sweet potato germplasm resources and offers a reference to facilitate the discovery of important genes to boost sweet potato breeding.

Childhood asthma diagnoses declined during the COVID-19 pandemic in the United States.

BACKGROUND: Prior studies have documented declines in pediatric asthma exacerbations and asthma-related health care utilization during the COVID-19 pandemic, but less is known about the incidence of asthma during the pandemic. METHODS: We conducted a retrospective cohort study of children under age 18 without a prior diagnosis of asthma within a large US commercial claims database. Incident asthma was defined using a combination of diagnosis codes, location of services, and medication dispensing. Crude quarterly rates of asthma diagnosis per 1000 children were calculated, and the incidence rate ratio and 95% confidence interval were estimated for newly diagnosed asthma during versus before the pandemic using negative binomial regression, adjusted for age, sex, region, and season. RESULTS: Compared with 3 years prior to the pandemic, crude incident diagnosis rates of asthma decreased by 52% across the first four quarters of the US pandemic. The covariate-adjusted pandemic-associated incidence rate ratio was 0.47 (95% confidence interval 0.43, 0.51). CONCLUSIONS: New diagnoses of childhood asthma in the US declined by half during the first year of the pandemic. These findings raise important questions whether pandemic-related changes in infectious or other triggers truly altered the incidence of childhood asthma beyond the well-described disruptions in healthcare access.

Efficacy of an internet-based cognitive behavioral therapy for subthreshold depression among Chinese adults: a randomized controlled trial.

BACKGROUND: Subthreshold depression (sD) negatively impacts well-being and psychosocial function and is more prevalent compared with major depressive disorder (MDD). However, as adults with sD are less likely to seek face-to-face intervention, internet-based cognitive-behavioral therapy (ICBT) may overcome barriers of accessibility to psychotherapy. Although several trials explored the efficacy of ICBT for sD, the results remain inconsistent. This study evaluated whether ICBT is effective in reducing depressive symptoms among Chinese adults with sD. METHODS: A randomized controlled trial was performed. The participants were randomly assigned to 5 weeks of ICBT, group-based face-to-face cognitive-behavioral therapy (CBT), or a waiting list (WL). Assessments were conducted at baseline, post-intervention and at a 6-month follow-up. The primary outcome measured depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D). Outcomes were analyzed using a mixed-effects model to assess the effects of ICBT. RESULTS: ICBT participants reported greater reductions on all the outcomes compared to the WL group at post-intervention. The ICBT group showed larger improvement on the Patient Health Questionnaire-9 (PHQ-9) at post-intervention (d = 0.12) and at follow-up (d = 0.10), and with CES-D at post-intervention (d = 0.06), compared to the CBT group. CONCLUSIONS: ICBT is effective in reducing depressive symptoms among Chinese adults with sD, and improvements in outcomes were sustained at a 6-month follow-up. Considering the low rates of face-to-face psychotherapy, our findings highlight the considerable potential and implications for the Chinese government to promote the use of ICBT for sD in China.

ScRNA-seq links dental fibroblasts heterogeneity with mechanoresponsiveness.

BACKGROUND AND OBJECTIVE: Periodontal ligament (PDL) and dental pulp (DP) share a common origin but have distinct biological and mechanical functions. To what extent the mechanoresponsive property of PDL can be attributed to its unique transcriptional profiles of cellular heterogeneity is unclear. This study aims to decipher cellular heterogeneity and distinct mechanoresponsive characteristics of odontogenic soft tissues and their underlying molecular mechanisms. MATERIALS AND METHODS: A single-cell comparison of digested human periodontal ligament (PDL) and dental pulp (DP) was performed using scRNA-seq. An in vitro loading model was constructed to measure mechanoresponsive ability. Dual-luciferase assay, overexpression, and shRNA knockdown were used to investigate the molecular mechanism. RESULTS: Our results demonstrate striking fibroblast heterogeneity across and within human PDL and DP. We demonstrated that a tissue-specific subset of fibroblasts existed in PDL exhibiting high expression of mechanoresponsive extracellular matrix (ECM) genes, which was verified by an in vitro loading model. ScRNA-seq analysis indicated a particularly enriched regulator in PDL-specific fibroblast subtype, Jun Dimerization Protein 2 (JDP2). Overexpression and knockdown of JDP2 extensively regulated the downstream mechanoresponsive ECM genes in human PDL cells. The force loading model demonstrated that JDP2 responded to tension and that knockdown of JDP2 effectively inhibited the mechanical force-induced ECM remodeling. CONCLUSIONS: Our study constructed the PDL and DP ScRNA-seq atlas to demonstrate PDL and DP fibroblast cellular heterogeneity and identify a PDL-specific mechanoresponsive fibroblast subtype and its underlying mechanism.

Regulation of stability and density of energetic materials via isomerism.

Selective regulation of stability and density via isomerism is a promising strategy for developing energetic materials. In this work, we selectively introduced dinitromethyl groups at different positions of 4-nitro-1,2,3-triazole. The regional heterogeneity endows a high crystal density by virtue of the dense packing; on the other hand, it changes the charge distribution in the molecule, and reinforces the hydrogen bonding interactions, all of which stabilize the material. The resulting compounds exhibit excellent detonation properties and impact sensitivity that are comparable to those of HMX (Dv = 9250 m s-1 and IS = 10 J).

A Streptomyces Cytochrome P450 Enzyme Catalyzes Regiospecific C2-Guaninylation for the Synthesis of Diverse Guanitrypmycin Analogs.

Heterologous expression of a cdps-p450 locus from Streptomyces sp. NRRL S-1521 led to the identification of guanitrypmycin D1, a new guaninylated diketopiperazine. The cytochrome P450 GutD1521 catalyzed the regiospecific transfer of guanine to C-2 of the indole ring of cyclo-(l-Trp-l-Tyr) via a C-C linkage and represents a new chemical transformation within this enzyme class. Furthermore, GutD1521 efficiently accepts several other tryptophan-containing cyclodipeptides or derivatives for regiospecific coupling with guanine, thus generating different guanitrypmycin analogs.

Lycium barbarum polysaccharide-glycoprotein promotes osteogenesis in hPDLSCs via ERK activation.

OBJECTIVE: A lack of relevant research on Lycium barbarum polysaccharide-glycoprotein (LBP) application in oral diseases. Here, we focused on the effect of LBP on osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and periodontitis bone loss. METHODS: Human periodontal ligament stem cells (hPDLSCs) were isolated and identified by flow cytometry. Alkaline phosphatase (ALP) activity, Alizarin Red staining, and combined qPCR and Western blot analyses were performed to elucidate the effects of LBP on the osteogenic potential of hPDLSCs. In vivo experiments were performed with the treatment of LBP in rat periodontal model. MicroCT scanning and histological analysis were conducted to evaluate osteogenesis in situ. RESULTS: Human periodontal ligament stem cells (hPDLSCs) were successfully isolated and identified with CD90, CD29, and CD45. LBP enhanced hPDLSCs proliferation and migration and promoted RUNX2, ALP, Collagen I, and Osteocalcin expression through activating the ERK1/2 signaling pathway in vitro. The inflammatory factors, including interleukin 6 (IL-6) and interleukin 8 (IL-8) were reduced after LBP treatment. Alveolar bone resorption was significantly decreased in the LBP-treated groups in vivo, and osteoclast was markedly decreased by LBP application. CONCLUSION: LBP promoted hPDLSC osteogenesis by targeting the ERK1/2 signaling pathway and reverse bone loss by reducing inflammation. These findings provided latent hope for LBP application in periodontal therapy.

Bone marrow mesenchymal stem cell-derived exosomes loaded with miR-26a through the novel immunomodulatory peptide DP7-C can promote osteogenesis.

PURPOSE: As small bioactive molecules, exosomes can deliver osteogenesis-related miRNAs to target cells and promote osteogenesis. This study aimed to investigate miR-26a as a therapeutic cargo to be loaded into bone marrow stromal cell exosomes through a novel immunomodulatory peptide (DP7-C). METHODS: After transfecting BMSCs with DP7-C as a transfection agent, exosomes were extracted by ultracentrifugation from the culture supernatant of miR-26a-modified BMSCs. We then characterized and identified the engineered exosomes. The effect of the engineered exosomes on osteogenesis was then evaluated in vitro and in vivo, including transwell, wound healing, modified alizarin red staining, western blot, real-time quantitative PCR, and experimental periodontitis assays. Bioinformatics and data analyses were conducted to investigate the role of miR-26a in bone regeneration. RESULTS: The DP7-C/miR-26a complex successfully transfected miR-26a into BMSCs and stimulated them to release more than 300 times the amount of exosomes overexpressing miR-26a compared with the ExoNC group. Furthermore, exosomes loaded with miR-26a could enhance proliferation, migration, and osteogenic differentiation of BMSCs in vitro compared with the ExoNC and blank groups. In vivo, the ExomiR-26a group inhibited the destruction of periodontitis compared with the ExoNC and blank groups, as revealed by HE staining. Micro-CT indicated that treatment of ExomiR-26a increased the percent bone volume and the bone mineral density compared with those of the ExoNC (P < 0.05) and blank groups (P < 0.001). Target gene analysis indicated that the osteogenic effect of miR-26a is related to the mTOR pathway. CONCLUSION: miR-26a can be encapsulated into exosomes through DP7-C. Exosomes loaded with miR-26a can promote osteogenesis and inhibit bone loss in experimental periodontitis and serve as the foundation for a novel treatment strategy.

A case report and literature review on respiratory failure with immune checkpoint inhibitors: a life-threatening adverse event.

Neuromuscular associated respiratory failure is a rare toxicity of immunotherapy for malignant tumors. In most cases, it may overlap with the symptoms of the primary disease or myocarditis, myositis and myasthenia gravis, resulting in difficult etiological diagnosis. Early detection and optimal treatment are still topics that need attention. Here, a case of 51-year-old male lung cancer patient with sintilimab-associated myasthenia gravis, myositis, and myocarditis overlap syndrome involving the diaphragm who developed severe type II respiratory failure was reported. After high-dose methylprednisolone, immunoglobulin and pyridostigmine intravenous injection with non-invasive positive pressure ventilation, the patient's symptoms improved significantly and was discharged. One year later, the patient received immunotherapy again due to tumor progression. After 53 days, he developed dyspnea again. Chest X-ray demonstrated marked elevation of the diaphragm, and the electromyogram demonstrated dysfunction of diaphragm. With rapid diagnosis and timely treatment, the patient was finally discharged safely. A comprehensive search of PubMed, EMBASE was performed to identify all previously reported cases of immune checkpoint inhibitors-associated respiratory failure. The potential mechanisms of respiratory failure caused by ICI-associated diaphragmatic dysfunction may be related to T cell-mediated immune disturbances and we proposed possible diagnostic processes. For patients with unexplained respiratory failure who are receiving immunotherapy, standardized diagnostic strategies should be implemented immediately on admission before deciding whether to conduct a more invasive diagnostic procedure or empirical treatment.

Telemedicine in the Battle with 2019 Novel Coronavirus Disease (COVID-19) in Henan Province, China: A Narrative Study.

Background and Objectives: Based on practical services of the Henan Province Telemedicine Center (HTCC), the purpose of this study is to investigate the design, construction, implementation, and application effect of a specific telemedicine system in response to the coronavirus disease 2019 (COVID-19). Methods: Data on COVID-19 cases from December 31, 2019, through October 17, 2022, were collected from official websites. Data and information of telemedicine services related to COVID-19 in HTCC were collected and analyzed, and relevant graphical representations were plotted. Results: All the 147 COVID-19 designated hospitals in the Henan Province were covered by the specific telemedicine system. The cities near to the Hubei Province in the south of Henan tended to be with more COVID-19 cases, where more COVID-19-related telemedicine services were conducted. For the telemedicine system, function modules, including real-time monitoring, command and dispatch, intractable cases transfer, remote guidance, and data sharing, were designed and realized to deal with COVID-19. Through the system, telemedicine services involved COVID-19 such as epidemic surveillance, emergency rescue, case discussion, diagnosis and treatment, remote ward-round, and distance education were performed. During the period between February 2 and March 3, 2020, 646 COVID-19 patients were served by the telemedicine system, with an improvement rate of 73.2%. Conclusions: Telemedicine can improve the diagnosis and treatment of COVID-19 patients, which play a helpful role in curbing the COVID-19 epidemic. Given the current global COVID-19 pandemic and the potential re-emerge of novel zoonotic pathogens in the future, the use of telemedicine would be imperative to fight against the pandemic.

Impact of the COVID-19 Pandemic on the Management of Juvenile Idiopathic Arthritis: Analysis of United States Commercial Insurance Data.

BACKGROUND/OBJECTIVE: Given limited information on health care and treatment utilization for juvenile idiopathic arthritis (JIA) during the pandemic, we studied JIA-related health care and treatment utilization in a commercially insured retrospective US cohort. METHODS: We studied rates of outpatient visits, new disease-modifying antirheumatic drug (DMARD) initiations, intra-articular glucocorticoid injections (iaGC), dispensed oral glucocorticoids and opioids, DMARD adherence, and DMARD discontinuation by quarter in March 2018-February 2021 (Q1 started in March). Incident rate ratios (IRR, pandemic vs prepandemic) with 95% confidence intervals (CIs) were estimated using multivariable Poisson or Quasi-Poisson models stratified by diagnosis recency (incident JIA, <12 months ago; prevalent JIA, ≥12 months ago). RESULTS: Among 1294 children diagnosed with JIA, total and in-person outpatient visits for JIA declined during the pandemic (IRR, 0.88-0.90), most markedly in Q1 2020. Telemedicine visits, while higher during the pandemic, declined from 21% (Q1) to 13% (Q4) in 2020 to 2021. During the pandemic, children with prevalent JIA, but not incident JIA, had lower usage of iaGC (IRR, 0.60; 95% CI, 0.34-1.07), oral glucocorticoids (IRR, 0.47; 95% CI, 0.33-0.67), and opioids (IRR, 0.44; 95% CI, 0.26-0.75). Adherence to and discontinuation of DMARDs was similar before and during the pandemic. CONCLUSIONS: In the first year of the pandemic, visits for JIA dropped by 10% to 12% in commercially insured children in the United States, declines partly mitigated by use of telemedicine. Pandemic-related declines in intra-articular glucocorticoids, oral glucocorticoids, and opioids were observed for children with prevalent, but not incident, JIA. These changes may have important implications for disease control and quality of life.

Exploration of molecular mechanism of intraspecific cross-incompatibility in sweetpotato by transcriptome and metabolome analysis.

Cross-incompatibility, frequently happening in intraspecific varieties, has seriously restricted sweetpotato breeding. However, the mechanism of sweetpotato intraspecific cross-incompatibility (ICI) remains largely unexplored, especially for molecular mechanism. Treatment by inducible reagent developed by our lab provides a method to generate material for mechanism study, which could promote incompatible pollen germination and tube growth in the ICI group. Based on the differential phenotypes between treated and untreated samples, transcriptome and metabolome were employed to explore the molecular mechanism of sweetpotato ICI in this study, taking varieties 'Guangshu 146' and 'Shangshu 19', a typical incompatible combination, as materials. The results from transcriptome analysis showed oxidation-reduction, cell wall metabolism, plant-pathogen interaction, and plant hormone signal transduction were the essential pathways for sweetpotato ICI regulation. The differentially expressed genes (DEGs) enriched in these pathways were the important candidate genes to response ICI. Metabolome analysis showed that multiple differential metabolites (DMs) involved oxidation-reduction were identified. The most significant DM identified in comparison between compatible and incompatible samples was vitexin-2-O-glucoside, a flavonoid metabolite. Corresponding to it, cytochrome P450s were the most DEGs identified in oxidation-reduction, which were implicated in flavonoid biosynthesis. It further suggested oxidation-reduction play an important role in sweetpotato ICI regulation. To validate function of oxidation-reduction, reactive oxygen species (ROS) was detected in compatible and incompatible samples. The green fluorescence was observed in incompatible but not in compatible samples. It indicated ROS regulated by oxidation-reduction is important pathway to response sweetpotato ICI. The results in this study would provide valuable insights into molecular mechanisms for sweetpotato ICI.

Establishment of Full-Length cDNA Clones and an Efficient Oral Infection Model for Feline Coronavirus in Cats.

Feline infectious peritonitis virus (FIPV) is the etiologic agent of feline infectious peritonitis (FIP) and causes fatal disease in cats of almost all ages. Currently, there are no clinically approved drugs or effective vaccines for FIP. Furthermore, the pathogenesis of FIP is still not fully understood. There is an urgent need for an effective infection model of feline infectious peritonitis induced by FIPV. Here, we constructed a field type I FIPV full-length cDNA clone, pBAC-QS, corresponding to the isolated FIPV QS. By replacing the FIPV QS spike gene with the commercially available type II FIPV 79-1146 (79-1146_CA) spike gene, we established and rescued a recombinant virus, designated rQS-79. Moreover, we constructed 79-1146_CA infectious full-length cDNA pBAC-79-1146_CA, corresponding to recombinant feline coronavirus (FCoV) 79-1146_CA (r79-1146_CA). In animal experiments with 1- to 2-year-old adult cats orally infected with the recombinant virus, rQS-79 induced typical FIP signs and 100% mortality. In contrast to cats infected with rQS-79, cats infected with 79-1146_CA did not show obvious signs. Furthermore, by rechallenging rQS-79 in surviving cats previously infected with 79-1146_CA, we found that there was no protection against rQS-79 with different titers of neutralizing antibodies. However, high titers of neutralizing antibodies may help prolong the cat survival time. Overall, we report the first reverse genetics of virulent recombinant FCoV (causing 100% mortality in adult cats) and attenuated FCoV (causing no mortality in adult cats), which will be powerful tools to study pathogenesis, antiviral drugs, and vaccines for FCoV. IMPORTANCE Tissue- or cell culture-adapted feline infectious peritonitis virus (FIPV) usually loses pathogenicity. To develop a highly virulent FIPV, we constructed a field isolate type I FIPV full-length clone with the spike gene replaced by the 79-1146 spike gene, corresponding to a virus named rQS-79, which induces high mortality in adult cats. rQS-79 represents the first described reverse genetics system for highly pathogenic FCoV. By further constructing the cell culture-adapted FCoV 79-1146_CA, we obtained infectious clones of virulent and attenuated FCoV. By in vitro and in vivo experiments, we established a model that can serve to study the pathogenic mechanisms of FIPV. Importantly, the wild-type FIPV replicase skeleton of serotype I will greatly facilitate the screening of antiviral drugs, both in vivo and in vitro.

Fear of progression and its associated factors in parents of children undergoing cancer treatment: A cross-sectional study.

OBJECTIVE: Fear of progression (FoP) is a common psychosocial problem among adult cancer patients, but data on parents of children undergoing cancer treatment are scarce. This study aimed to determine the prevalence of FoP in parents of children undergoing cancer treatment and explore the associated factors. METHODS: Overall, 285 parents of children undergoing cancer treatment were recruited from three general hospitals in China. FoP in the parents was assessed using the Chinese version of the Fear of Progression Questionnaire-parent version (FoP-Q-SF/PR). Other questionnaires included the Self-Compassion Scale, Pittsburgh Sleep Quality Index, Posttraumatic Stress Disorder Checklist-Civilian Version, and items on socio-demographic and medical characteristics. Pearson correlation and multiple linear regression analysis were used to identify factors associated with FoP. RESULTS: A total of 75.1% of the participants showed dysfunctional levels of FoP. The mean FoP-Q-SF/PR score was 39.98 (standard deviation = 9.18). Parental FoP was significantly associated with a shorter time since diagnosis, lower levels of self-compassion, poor sleep quality, and severe posttraumatic stress symptoms (Adjusted R Squared = 0.369, F = 12.838, p < 0.01). CONCLUSIONS: FoP is a frequently reported problem among parents of children undergoing cancer treatment. In this cohort, parents of children with a shorter time since cancer diagnosis were at higher risk of suffering from FoP. Interventions to enhance self-compassion, improve sleep quality, and mitigate posttraumatic stress symptoms may help with the psychological adjustment and well-being of parents whose children are undergoing cancer treatment.