Arabidopsis HEMERA/pTAC12 initiates photomorphogenesis by phytochromes.

Light plays a profound role in plant development, yet how photoreceptor excitation directs phenotypic plasticity remains elusive. One of the earliest effects of light is the regulated translocation of the red/far-red photoreceptors, phytochromes, from the cytoplasm to subnuclear foci called phytochrome nuclear bodies. The function of these nuclear bodies is unknown. We report the identification of hemera, a seedling lethal mutant of Arabidopsis with altered phytochrome nuclear body patterns. hemera mutants are impaired in all phytochrome responses examined, including proteolysis of phytochrome A and phytochrome-interacting transcription factors. HEMERA was identified previously as pTAC12, a component of a plastid complex associated with transcription. Here, we show that HEMERA has a function in the nucleus, where it acts specifically in phytochrome signaling, is predicted to be structurally similar to the multiubiquitin-binding protein, RAD23, and can partially rescue yeast rad23mutants. Together, these results implicate phytochrome nuclear bodies as sites of proteolysis.

Juveniles, young adults, and infants with hepatitis B virus infection: A genomic study.

Integration of hepatitis B virus (HBV) DNA into the human genome is recognized as an oncogenic factor and a barrier to hepatitis B cure. In the study, biopsy liver tissues were collected from adolescents and young adults with acute HBV infection younger than or equal to 35 years of age and from HBV-infected infant patients younger than or equal to 6 months of age. A high-throughput sequencing method was used to detect HBV DNA integration. Totally, 12 adolescents, young adults, and 6 infants were included. Among the 12 patients with acute HBV infection, immunohistochemical staining of intrahepatic hepatitis B surface antigen for all displayed negative results, and no HBV DNA integrants in the hepatocyte DNA were confirmed. All infant patients had elevated levels of alanine aminotransferase and high levels of serum HBV DNA. Numerous gene sites of hepatocyte DNA were integrated by HBV DNA for each infant patient, ranging from 120 to 430 integration sites. The fragile histidine triad gene was the high-frequency integrated site in the intragenic region for infant patients. In conclusion, hepatocyte DNA is integrated by HBV DNA in babies with active hepatitis B but seems seldom affected among adolescents and young adults with acute HBV infection. Infantile hepatitis B should be taken seriously considering abundant HBV DNA integration events.

Cognition of nursing translational medical research among nursing practitioners in China.

BACKGROUND: Nursing translational research (TR) begins with clinical discovery and medical research and leads to clinical application in patients. TR is key to improving nursing quality and developing the nursing profession. However, its development in China remains limited, and the reasons for this are unclear. We aim to enhance the recognition of nursing TR among nursing practitioners in China by exploring their cognition about nursing TR and associated influences. METHODS: We distributed an internet-based questionnaire to 683 nursing practitioners between February 13 and March 15, 2023. We analyzed the characteristics and cognition of nursing TR using descriptive statistics, the chi-squared test, Fisher's exact test, the Wilcoxon rank-sum test, Kruskal-Wallis H test, and stepwise logistic regression analysis. The majority (79.65%) of nursing practitioners who responded to the questionnaire were willing to participate in nursing TR. FINDINGS: Nursing practitioners with a higher educational level, stronger recognition of the importance of nursing TR, and stronger recognition of transdisciplinary nursing TR were more willing to participate in nursing TR. DISCUSSION: The results of this study can accelerate nursing practitioners' willingness to participate in nursing TR. APPLICATION TO PRACTICE: We identified strategies to promote TR: provide further education, optimize courses in higher education, disseminate information, provide guidance on the importance of nursing TR, and establish a nursing TR platform with appropriate potential collaborators.

Natural variation of MS2 confers male fertility and drives hybrid breeding in soybean.

A complete and genetically stable male sterile line with high outcrossing rate is a prerequisite for the development of commercial hybrid soybean. It was reported in the last century that the soybean male sterile ms2 mutant has the highest record with seed set. Here we report the cloning and characterization of the MS2 gene in soybean, which encodes a protein that is specifically expressed in the anther. MS2 functions in the tapetum and microspore by directly regulating genes involved in the biosynthesis of secondary metabolites and the lipid metabolism, which is essential for the formation of microspore cell wall. Through comparison of the field performance with the widely used male sterile mutants in the same genetic background, we demonstrated that the ms2 mutant conducts the best in outcrossing rate and makes it an ideal tool in building a cost-effective hybrid system for soybean.

Male sterility and hybrid breeding in soybean.

Hybrid breeding can help us to meet the challenge of feeding a growing world population with limited agricultural land. The demand for soybean is expected to grow; however, the hybrid soybean is still in the process of commercialization even though considerable progress has been made in soybean genome and genetic studies in recent years. Here, we summarize recent advances in male sterility-based breeding programs and the current status of hybrid soybean breeding. A number of male-sterile lines with cytoplasmic male sterility (CMS), genic-controlled photoperiod/thermo-sensitive male sterility, and stable nuclear male sterility (GMS) have been identified in soybean. More than 40 hybrid soybean varieties have been bred using the CMS three-line hybrid system and the cultivation of hybrid soybean is still under way. The key to accelerating hybrid soybean breeding is to increase the out-crossing rate in an economical way. This review outlines current problems with the hybrid soybean breeding systems and explores the current efforts to make the hybrid soybean a commercial success.

Non-Directional Property of Human-Body Communication Channel for Implantable Device Application.

In this paper, we present the properties of a communication channel used for implantable devices. The human-body communication (HBC) channel was proposed for data communication in implantable devices. The impulse response was measured using a channel-mimicking model, which mimics electrical losses caused by human body tissues. Furthermore, we compared two types of channel-mimicking models to evaluate their applicability depending on the measurement environment. The resultant impulse responses of the HBC channel showed that HBC does not cause severe changes in the channel properties even when the implantable device is rotated.

Comprehensive mapping of abiotic stress inputs into the soybean circadian clock.

The plant circadian clock evolved to increase fitness by synchronizing physiological processes with environmental oscillations. Crop fitness was artificially selected through domestication and breeding, and the circadian clock was identified by both natural and artificial selections as a key to improved fitness. Despite progress in Arabidopsis, our understanding of the crop circadian clock is still limited, impeding its rational improvement for enhanced fitness. To unveil the interactions between the crop circadian clock and various environmental cues, we comprehensively mapped abiotic stress inputs to the soybean circadian clock using a 2-module discovery pipeline. Using the "molecular timetable" method, we computationally surveyed publicly available abiotic stress-related soybean transcriptomes to identify stresses that have strong impacts on the global rhythm. These findings were then experimentally confirmed using a multiplexed RNA sequencing technology. Specific clock components modulated by each stress were further identified. This comprehensive mapping uncovered inputs to the plant circadian clock such as alkaline stress. Moreover, short-term iron deficiency targeted different clock components in soybean and Arabidopsis and thus had opposite effects on the clocks of these 2 species. Comparing soybean varieties with different iron uptake efficiencies suggests that phase modulation might be a mechanism to alleviate iron deficiency symptoms in soybean. These unique responses in soybean demonstrate the need to directly study crop circadian clocks. Our discovery pipeline may serve as a broadly applicable tool to facilitate these explorations.

Collaborative relationships in translational medical research among Chinese clinicians: an internet-based cross-sectional survey.

BACKGROUND: This study aimed to explore the collaborative relationship in translational medical research from the perspective of clinicians in China. The findings are expected to help practitioners optimize and experience the greatest advantages of collaboration. METHODS: We conducted a national internet-based survey from July 29 to October 12, 2020. Of the 806 responses, 804 were completed with valid responses (valid response rate = 99.8%). The collected data were presented as descriptive statistics and analyzed using nonparametric tests (including the Wilcoxon rank test and Kruskal-Wallis H test) and stepwise logistic regression. RESULTS: Of the 804 participants, 733 were either willing or very willing to collaborate in translational medical research. Clinicians' willingness was influenced by their current research type, role in current translational medical research, burdens of their present research, preferred partners for collaboration at the institutional or individual level, and preferences for independent or dependent relationships. CONCLUSIONS: Clinicians should evaluate their time, role, burdens, personal preferences for research relationships, and appropriate partners based on their current translational medical research and its goals, before deciding to collaborate.

Biopsy-proven liver cirrhosis in young children: A 10-year cohort study.

Young children with liver cirrhosis have a significantly high risk of mortality. However, there are few studies regarding early childhood-onset cirrhosis. This study aims to explore the causes, clinical findings and prognosis of biopsy-proven cirrhosis in infants, toddlers and preschoolers. We enroled young children with biopsy-proven cirrhosis from January 2010. Till January 2020, the study has been going on for 10 years. A total of 139 cirrhotic children were enrolled, including 87 boys and 52 girls. The median age at initially histological diagnosis of cirrhosis was 2 years old (range: 1 month-6 years). Sixty-two patients reported yellowish discoloration of sclera and/or skin as an initial symptom. Ninety-three patients had definite aetiologies while 46 had indeterminate causes. Among the confirmed cases, 31 had hepatitis B virus (HBV) infection, accounting for 33.3%. Subsequently, glycogen storage disease was diagnosed in 16 cases and Wilson disease in 14 cases. In these patients with HBV infection, nine finally achieved hepatitis B surface antigen (HBsAg) loss (29.0%) after effective antiviral therapy during the follow-up. Logistic regression revealed that baseline alanine aminotransferase (odds ratio 1.008, p = 0.028) was the independent predictor of HBsAg loss. Furthermore, one patient who underwent second biopsies showed histological reverse. HBV infection is an important cause of paediatric cirrhosis in our study. The pathogenesis of HBV-related cirrhosis in early childhood deserves further studies.

Two homologous LHY pairs negatively control soybean drought tolerance by repressing the abscisic acid responses.

The circadian clock plays essential roles in diverse plant biological processes, such as flowering, phytohormone biosynthesis and abiotic stress responses. The manner in which circadian clock genes regulate drought stress responses in model plants has been well established, but comparatively little is known in crop species, such as soybean, a major global crop. This paper reports that the core clock components GmLHYs, the orthologues of CCA1/LHY in Arabidopsis, negatively control drought tolerance in soybean. The expressions of four GmLHYs were all induced by drought, and the quadruple mutants of GmLHYs demonstrated significantly improved drought tolerance. Transcriptome profiling suggested that the abscisic acid (ABA) signaling pathway is regulated by GmLHYs to respond to drought tolerance. Genetic dissections showed that two homologous pairs of LHY1a and LHY1b redundantly control the drought response. Functional characterization of LHY1a and LHY1b in Arabidopsis and soybean further supported the notion that GmLHYs can maintain cellular homeostasis through the ABA signaling pathway under drought stress. This study improves our understanding of the underlying molecular mechanisms on soybean drought tolerance. Furthermore, the two homologues of LHY1a and LHY1b provide alternative targets for genome editing to rapidly generate mutant alleles in elite soybean cultivars to enhance their drought tolerance.

Effect of temperature and its interaction with other meteorological factors on bacillary dysentery in Jilin Province, China.

Bacterial dysentery (BD) brings a major disease burden to developing countries. Exploring the influence of temperature and its interaction with other meteorological factors on BD is significant for the prevention and early warning of BD in the context of climate change. Daily BD cases and meteorological data from 2008 to 2018 were collected in all nine prefecture-level cities in Jilin Province. A one-stage province-level model and a two-stage city-specific multivariate meta-pooled level distributed lag non-linear model were established to explore the correlation between temperature and BD, then the weather-stratified generalised additive model was used to test the interaction. During the study period, a total of 26 971 cases of BD were developed. The one-stage and two-stage cumulative dose-response 'J' curves overlapped, and results showed a positive correlation between temperature and BD with a 1-6 days lag effect. Age group ⩾5 years was found to be more sensitive to the effects. Moreover, there was a significant interaction between temperature, humidity and precipitation (P = 0.004, 0.002, respectively) on BD under high temperature (>0 °C), reminding residents and policymakers to pay attention to the prevention of BD in situations with both high temperature and humidity, high temperature and precipitation during the temperate monsoon climate.

Evaluating the effectiveness of measures to control the novel coronavirus disease 2019 in Jilin Province, China.

BACKGROUND: Based on differences in populations and prevention and control measures, the spread of new coronary pneumonia in different countries and regions also differs. This study aimed to calculate the transmissibility of coronavirus disease 2019 (COVID-19), and to evaluate the effectiveness of measures to control the disease in Jilin Province, China. METHODS: The data of reported COVID-19 cases were collected, including imported and local cases from Jilin Province as of March 14, 2019. A Susceptible-Exposed-Infectious-Asymptomatic-Recovered/Removed (SEIAR) model was developed to fit the data, and the effective reproduction number (Reff) was calculated at different stages in the province. Finally, the effectiveness of the measures was assessed. RESULTS: A total of 97 COVID-19 infections were reported in Jilin Province, among which 45 were imported infections (including one asymptomatic infection) and 52 were local infections (including three asymptomatic infections). The model fit the reported data well (R2 = 0.593, P < 0.001). The Reff of COVID-19 before and after February 1, 2020 was 1.64 and 0.05, respectively. Without the intervention taken on February 1, 2020, the predicted cases would have reached a peak of 177,011 on October 22, 2020 (284 days from the first case). The projected number of cases until the end of the outbreak (on October 9, 2021) would have been 17,129,367, with a total attack rate of 63.66%. Based on the comparison between the predicted incidence of the model and the actual incidence, the comprehensive intervention measures implemented in Jilin Province on February 1 reduced the incidence of cases by 99.99%. Therefore, according to the current measures and implementation efforts, Jilin Province can achieve good control of the virus's spread. CONCLUSIONS: COVID-19 has a moderate transmissibility in Jilin Province, China. The interventions implemented in the province had proven effective; increasing social distancing and a rapid response by the prevention and control system will help control the spread of the disease.

Sensitive and Selective Measurement of Hydroxyl Radicals at Subcellular Level with Tungsten Nanoelectrodes.

Hydroxyl radical (•OH) is an essential reactive oxygen species involved in critical cell functions. However, the mechanisms controlling its subcellular localization and intracellular level during health and disease remain poorly understood. This is due to the challenge of detecting •OH that are highly reactive and consequently short-lived (in vivo half-life of ∼10-9 s). Herein, we present tungsten nanoelectrodes functionalized with stable 1-hexanethiol (HAT) for selective and sensitive detection of •OH at the subcellular level via the destruction of the self-assembled monolayer of HAT on the nanoelectrode tip. Taking advantage of the ultrasmall nanotip and the super mechanical toughness, the tungsten nanoelectrode could easily penetrate a single living cell without inducing any observable damage. Controlled by a high precision micromanipulator, the •OH level in RAW 264.7 murine macrophages under amyloid ß (Aß) induced oxidative stress were first investigated by the nanoelectrodes at the subcellular level. Moreover, the results revealed the cordycepin-mediated cytoprotection of macrophages through modulation of PI3K/Akt pathway activity and introduction of heme oxygenase-1 (HO-1). We believe that the developed nanoelectrochemical method has shown great capacities for the study of potential drugs for therapeutic intervention of Alzheimer's disease.

De novo combination antiviral therapy in e antigen-negative chronic hepatitis B virus-infected paediatric patients with advanced fibrosis.

To date, studies that focus on treatment of e antigen-negative chronic hepatitis B virus-infected children with advanced fibrosis are extremely limited. This puts these patients at risk of rapid disease progression. Our study aimed to investigate the efficacy of combination antiviral therapy in this population. We prospectively enrolled treatment-naïve paediatric patients between 1 year and 12 years of age who had e antigen-negative chronic hepatitis B and histologically proven advanced fibrosis. All patients received de novo combination therapy with lamivudine (LAM) and interferon-α (IFN) for 12 months and then were clinically followed up. The main outcome measure was rate of serum hepatitis B surface antigen (HBsAg) loss at month 12 of treatment. A total of 14 paediatric patients were enrolled, including 9 boys and 5 girls. All patients achieved undetectable HBV DNA levels at month 9 of treatment. A total of 5 patients (35.7%) achieved HBsAg loss at month 12 and finally developed HBsAg seroconversion. Four patients who did not clear HBsAg underwent second liver biopsy, and histological evaluation revealed significant improvements in all of them. As a serum fibrosis marker, aspartate aminotransferase-to-platelet ratio index after 12-month treatment in the 14 patients showed a significant improvement compared with that at baseline (P = .0021). No serious adverse events were observed during the study. Combination antiviral therapy is beneficial to e antigen-negative chronic hepatitis B virus-infected paediatric patients with advanced fibrosis. Further studies with larger cohorts are required.

Control of unreasonable growth of medical expenses in public hospitals in Shanghai, China: a multi-agent system model.

BACKGROUND: This study aims to establish a multi-agent system model to provide accurate suggestions for the policy proposal of controlling the unreasonable growth of medical expenses charged by public hospitals in China. METHODS: A multi-agent system model was employed in this study. Agents of this model were divided into patients, doctors, medical institutions, the government, and medical insurance agencies. The model was composed of two subsystems: the disease and medical-seeking subsystem, and the medical expenses subsystem. Policy intervention experiments were conducted on patients' medical-seeking preferences, doctors' public welfare behaviors, and the government's financial investment. RESULTS: At present, medical expenses in China are unreasonable and keep increasing, and the proportion of medicine and physical examination expenses to total medical expenses for public hospitals is unreasonable. Intervention experiments suggested that expanding the promotion and application of the community first-visit system could rationalize patients' medical-seeking preferences, increasing doctors' incomes and reducing workload could significantly restrict doctors' over-prescription behaviors. Also, improving the government's financial investment could guide public hospitals to strengthen their commitment to public welfare responsibilities. These interventions could decrease the unreasonable growth of medical expenses of public hospitals. The combined intervention effects on suppliers, demanders, and the government were better than the effect of these agents independently. CONCLUSIONS: The main reasons for the unreasonable increase in patient medical expenses at public hospitals could be attributed to patients' unreasonable medical-seeking preferences, doctors' weak public welfare incentives, and the government's inadequate financial investment. Policy-makers should consider proposals to restrict and guide the behaviors of suppliers, demanders, and the government, simultaneously. The government should consider the feasibility, response speed, and implementation cost of policies as well.

Photoactivated phytochromes interact with HEMERA and promote its accumulation to establish photomorphogenesis in Arabidopsis.

Plant development is profoundly regulated by ambient light cues through the red/far-red photoreceptors, the phytochromes. Early phytochrome signaling events include the translocation of phytochromes from the cytoplasm to subnuclear domains called photobodies and the degradation of antagonistically acting phytochrome-interacting factors (PIFs). We recently identified a key phytochrome signaling component, HEMERA (HMR), that is essential for both phytochrome B (phyB) localization to photobodies and PIF degradation. However, the signaling mechanism linking phytochromes and HMR is unknown. Here we show that phytochromes directly interact with HMR to promote HMR protein accumulation in the light. HMR binds more strongly to the active form of phytochromes. This interaction is mediated by the photosensory domains of phytochromes and two phytochrome-interacting regions in HMR. Missense mutations in either HMR or phyB that alter the phytochrome/HMR interaction can also change HMR levels and photomorphogenetic responses. HMR accumulation in a constitutively active phyB mutant (YHB) is required for YHB-dependent PIF3 degradation in the dark. Our genetic and biochemical studies strongly support a novel phytochrome signaling mechanism in which photoactivated phytochromes directly interact with HMR and promote HMR accumulation, which in turn mediates the formation of photobodies and the degradation of PIFs to establish photomorphogenesis.

Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-ß Activity.

Asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly associated with respiratory syncytial virus (RSV), rhinovirus (RV) and influenza A virus (IAV) infection. The ensuing airway inflammation is resistant to the anti-inflammatory actions of glucocorticoids (GCs). Viral infection elicits transforming growth factor-ß (TGF-ß) activity, a growth factor we have previously shown to impair GC action in human airway epithelial cells through the activation of activin-like kinase 5 (ALK5), the type 1 receptor of TGF-ß. In the current study, we examine the contribution of TGF-ß activity to the GC-resistance caused by viral infection. We demonstrate that viral infection of human bronchial epithelial cells with RSV, RV or IAV impairs GC anti-inflammatory action. Poly(I:C), a synthetic analog of double-stranded RNA, also impairs GC activity. Both viral infection and poly(I:C) increase TGF-ß expression and activity. Importantly, the GC impairment was attenuated by the selective ALK5 (TGFßRI) inhibitor, SB431542 and prevented by the therapeutic agent, tranilast, which reduced TGF-ß activity associated with viral infection. This study shows for the first time that viral-induced glucocorticoid-insensitivity is partially mediated by activation of endogenous TGF-ß.

Cortisol limits selected actions of synthetic glucocorticoids in the airway epithelium.

Cortisol, a physiologic glucocorticoid (GC), is essential for growth and differentiation of the airway epithelium. Epithelial function influences inflammation in chronic respiratory diseases. Synthetic GCs, including inhaled corticosteroids, exert anti-inflammatory effects in airway epithelium by transactivation of genes and by inhibition of proinflammatory cytokine release. We examined the effect of cortisol on the actions of synthetic GCs in the airway epithelium, demonstrating that cortisol acts like a partial agonist at the GC receptor (GR), limiting GC-induced GR-dependent transcription in the BEAS-2B human bronchial epithelial cell line. Cortisol also limited the inhibition of granulocyte macrophage colony-stimulating factor release by synthetic GCs in TNF-α-activated BEAS-2B cells. The relevance of these findings is supported by observations on tracheal epithelium obtained from mice treated for 5 d with systemic GC, showing limitations in selected GC effects, including inhibition of IL-6. Moreover, gene transactivation by synthetic GCs was compromised by standard air-liquid interface (ALI) growth medium cortisol concentration (1.4 µM) in the ALI-differentiated organotypic culture of primary human airway epithelial cells. These findings suggest that endogenous corticosteroids may limit certain actions of synthetic pharmacological GCs and contribute to GC insensitivity, particularly when corticosteroid levels are elevated by stress.-Prodanovic, D., Keenan, C. R., Langenbach, S., Li, M., Chen, Q., Lew, M. J., Stewart, A. G. Cortisol limits selected actions of synthetic glucocorticoids in the airway epithelium.

HEMERA Couples the Proteolysis and Transcriptional Activity of PHYTOCHROME INTERACTING FACTORs in Arabidopsis Photomorphogenesis.

Phytochromes (phys) are red and far-red photoreceptors that control plant development and growth by promoting the proteolysis of a family of antagonistically acting basic helix-loop-helix transcription factors, the PHYTOCHROME-INTERACTING FACTORs (PIFs). We have previously shown that the degradation of PIF1 and PIF3 requires HEMERA (HMR). However, the biochemical function of HMR and the mechanism by which it mediates PIF degradation remain unclear. Here, we provide genetic evidence that HMR acts upstream of PIFs in regulating hypocotyl growth. Surprisingly, genome-wide analysis of HMR- and PIF-dependent genes reveals that HMR is also required for the transactivation of a subset of PIF direct-target genes. We show that HMR interacts with all PIFs. The HMR-PIF interaction is mediated mainly by HMR's N-terminal half and PIFs' conserved active-phytochrome B binding motif. In addition, HMR possesses an acidic nine-amino-acid transcriptional activation domain (9aaTAD) and a loss-of-function mutation in this 9aaTAD impairs the expression of PIF target genes and the destruction of PIF1 and PIF3. Together, these in vivo results support a regulatory mechanism for PIFs in which HMR is a transcriptional coactivator binding directly to PIFs and the 9aaTAD of HMR couples the degradation of PIF1 and PIF3 with the transactivation of PIF target genes.

Effect of Lactobacillus acidophilus KLDS 1.0738 on miRNA expression in in vitro and in vivo models of ß-lactoglobulin allergy.

This study aims to investigate the correlation between the ability of L. acidophilus to modulate miRNA expression and prevent Th17-dominated ß-lactoglobulin (ß-Lg) allergy. In vitro immunomodulation was evaluated by measuring splenocyte proliferation, Th17-related immune response and miRNA expression in ß-Lg-sensitized splenocytes cultured with live L. acidophilus. Next, the allergic mouse model was used to evaluate anti-allergy capability of lactobacilli. The ß-Lg challenge led to induction of up-regulation of miR-146a, miR-155, miR-21 and miR-9 expression in both in vivo and in vitro, along with increased Th17-related cytokine levels and mRNA expression of RORγt and IL-17. However, treatment of live L. acidophilus significantly suppressed hypersensitivity responses and Th17 cell differentiation. Moreover, administration of live L. acidophilus reduced expression of four miRNAs, especially miR-146a and miR-155. In addition, the decreased expression of the miRNAs in the spleen of the L. acidophilus-treated group was closely associated with decrease of IL-17 and RORγt mRNA expression.