Blue light-dependent interactions of CRY1 with GID1 and DELLA proteins regulate gibberellin signaling and photomorphogenesis in Arabidopsis.

Cryptochromes are blue light photoreceptors that mediate various light responses in plants and mammals. In Arabidopsis (Arabidopsis thaliana), cryptochrome 1 (CRY1) mediates blue light-induced photomorphogenesis, which is characterized by reduced hypocotyl elongation and enhanced anthocyanin production, whereas gibberellin (GA) signaling mediated by the GA receptor GA-INSENSITIVE DWARF1 (GID1) and DELLA proteins promotes hypocotyl elongation and inhibits anthocyanin accumulation. Whether CRY1 control of photomorphogenesis involves regulation of GA signaling is largely unknown. Here, we show that CRY1 signaling involves the inhibition of GA signaling through repression of GA-induced degradation of DELLA proteins. CRY1 physically interacts with DELLA proteins in a blue light-dependent manner, leading to their dissociation from SLEEPY1 (SLY1) and the inhibition of their ubiquitination. Moreover, CRY1 interacts directly with GID1 in a blue light-dependent but GA-independent manner, leading to the inhibition of the interaction between GID1 with DELLA proteins. These findings suggest that CRY1 controls photomorphogenesis through inhibition of GA-induced degradation of DELLA proteins and GA signaling, which is mediated by CRY1 inhibition of the interactions of DELLA proteins with GID1 and SCFSLY1, respectively.

Bridging therapy improves functional outcomes and reduces 90-day mortality compared with direct endovascular thrombectomy in patients with acute posterior ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: It remains unclear whether bridging therapy can achieve better neurologic outcomes than direct endovascular thrombectomy (EVT) in patients with posterior ischemic stroke. METHODS: We systematically searched PubMed, EMBASE, and Cochrane databases with posterior artery occlusion treated with bridging therapy vs. EVT. Efficacy was assessed based on functional independence at 90 days and successful recanalization, whereas safety was assessed by mortality, rate of symptomatic intracranial hemorrhage (sICH), and occurrence of any hemorrhage. All data were analyzed with Review Manager software v5.3 and the risk of bias was determined using the Methodological Index for Non-randomized Studies. RESULTS: We included 17 studies with a total of 3278 patients (1211 in the bridging therapy group and 2067 in the EVT group). Patients in the bridging group had a better functional outcome at 90 days, as evidenced by a higher proportion with a Modified Rankin Scale (mRS) score of 0-2 compared with the EVT group (odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.54-2.19, P < 0.01), while no difference in mRS score of 0-3 (OR = 1.18, 95% CI: 0.96-1.45, P = 0.11). Patients in the bridging therapy group also had lower 90-day mortality rate (OR = 0.75, 95% CI: 0.59-0.95, P = 0.02). There were no significant differences between groups in rates of successful recanalization (OR = 0.96, 95% CI: 0.74-1.25, P = 0.77), sICH (OR = 1.27, 95% CI: 0.86-1.89, P = 0.24), and hemorrhage (OR = 1.22, 95% CI: 0.60-2.50, P = 0.58). CONCLUSIONS: Among patients with posterior ischemic stroke, bridging therapy may be superior to EVT in achieving a good functional outcome and lowering the mortality without increasing the risks of hemorrhage.

Safety and efficacy of bone marrow mononuclear cell therapy for ischemic stroke recovery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cell-based therapy represents a potential treatment for ischemic stroke (IS). Here, we performed a systematic review and meta-analysis to summarize the evidence provided by randomized controlled trials (RCTs) for the transplantation of bone marrow mononuclear cells (BMMNCs) in patients with IS in any phase after stroke. METHODS: We searched several databases for relevant articles up to the 10th of March 2023, including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov. Subgroup analyses were implemented to evaluate the dose and route of BMMNC administration. Statistical data were analyzed by Review Manager version 5.3 software. RESULTS: Six RCTs were included in this article, including 177 patients who were treated by the transplantation of BMMNCs and 166 patients who received medical treatment. The three-month National Institutes of Health Stroke Scale (NIHSS) score indicated a favorable outcome for the BMMNC transplantation group (standardized mean difference (SMD), - 0.34; 95% confidence interval (CI), - 0.57 to - 0.11; P = 0.004). There were no significant differences between the two groups at six months post-transplantation with regards to NIHSS score (SMD 0.00; 95% CI - 0.26 to 0.27; P = 0.97), modified Rankin Scale (risk ratio (RR) 1.10; 95% CI 0.75 to 1.63; P = 0.62), Barthel Index change (SMD 0.68; 95% CI - 0.59 to 1.95; P = 0.29), and infarct volume change (SMD - 0.08; 95% CI - 0.42 to 0.26; P = 0.64). In addition, there was no significant difference between the two groups in terms of safety outcome (RR 1.24; 95% CI 0.80 to 1.91; P = 0.33). CONCLUSION: Our meta-analysis demonstrated that the transplantation of BMMNCs was safe; however, the efficacy of this procedure requires further validation in larger RTCs.

External stenting for saphenous vein grafts in coronary artery bypass grafting: A meta-analysis.

OBJECTIVES: Autologous saphenous vein grafts (SVGs) are the most commonly used bypass conduits in coronary artery bypass grafting (CABG) with multivessel coronary artery disease. Although external support devices for SVGs have shown promising outcomes, the overall efficacy and safety remains controversial. We aimed to evaluate external stenting for SVGs in CABG versus non-stented SVGs. METHODS: MEDLINE, EMBASE, Cochrane Library and clinicaltrails.gov were searched for randomized controlled trials (RCTs) to evaluate external-stented SVGs versus non-stented SVGs in CABG up to 31 August 2022. The risk ratio and mean difference with 95% confidence interval were analysed. The primary efficacy outcomes included intimal hyperplasia area and thickness. The secondary efficacy outcomes were graft failure (≥50% stenosis) and lumen diameter uniformity. RESULTS: We pooled 438 patients from three RCTs. The external stented SVGs group showed significant reductions in intimal hyperplasia area (MD: -0.78, p < 0.001, I2 = 0%) and thickness (MD: -0.06, p < 0.001, I2 = 0%) compared to the non-stented SVGs group. Meanwhile, external support devices improved lumen uniformity with Fitzgibbon I classification (risk ratio (RR):1.1595, p = 0.05, I2 = 0%). SVG failure rates were not increased in the external stented SVGs group during the short follow-up period (RR: 1.14, p = 0.38, I2 = 0%). Furthermore, the incidences of mortality and major cardiac and cerebrovascular events were consistent with previous reports. CONCLUSIONS: External support devices for SVGs significantly reduced the intimal hyperplasia area and thickness, and improved the lumen uniformity, assessed with the Fitzgibbon I classification. Meanwhile, they did not increase the overall SVG failure rate.

Dissolved organic matter evolution and straw decomposition rate characterization under different water and fertilizer conditions based on three-dimensional fluorescence spectrum and deep learning.

Straw returning is a sustainable way to utilize agricultural solid waste resources. However, incomplete decomposition of straw will cause harm to crop growth and soil quality. Currently, there is a lack of technology to timely monitor the rate of straw decomposition. Dissolved organic matter (DOM) is the most active organic matter in soil and straw is mainly immersed in the soil in the form of DOM. In order to formulate reasonable straw returning management measures , a timely monitoring method of straw decomposition rate was developed in the study. Three water treatment (60%-65%, 70%-75% and 80%-85% maximum field capacity) and two fertilizer (organic fertilizer and chemical fertilizer) were set up in the management of straw returning to the field. Litterbag method was used to monitor the weight loss rate of straw decomposition under different water and fertilizer conditions in strawberry growth stage. The changes of DOM components were determined by three-dimensional fluorescence spectroscopy (3D-EEM). From the faster decomposition period to the slower decomposition period, the main components of DOM changed from protein-like components to humus-like components. At the end of the experiment, the relative content of humus-like components under the treatment of organic fertilizer and moderate water was the highest. Convolutional neural network (CNN) combined with 3D-EEM was used to identify the decomposition speed of straw. The classification precision of neural network validation set and test are 85.7% and 81.2%, respectively. In order to predict the decomposition rate of straw under different water and fertilizer conditions, 3D-EEM data of DOM were used as the input of CNN, parallel factor analysis (PARAFAC) and fluorescence region integral (FRI), and dissolved organic carbon data were used as the input of dissolved organic carbon linear prediction. The prediction model based on CNN had the best effect (R2 = 0.987). The results show that this method can effectively identify the spectral characteristics and predict the decomposition rate of straw under different conditions of water and fertilizer, which is helpful to promote the efficient decomposition of straw.

Arabidopsis cryptochrome 1 undergoes COP1 and LRBs-dependent degradation in response to high blue light.

Arabidopsis cryptochrome 1 (CRY1) is an important blue light photoreceptor that promotes photomorphogenesis under blue light. The blue light photoreceptors CRY2 and phototropin 1, and the red/far-red light photoreceptors phytochromes B and A undergo degradation in response to blue and red light, respectively. This study investigated whether and how CRY1 might undergo degradation in response to high-intensity blue light (HBL). We demonstrated that CRY1 is ubiquitinated and degraded through the 26S proteasome pathway in response to HBL. We found that the E3 ubiquitin ligase constitutive photomorphogenic 1 (COP1) is involved in mediating HBL-induced ubiquitination and degradation of CRY1. We also found that the E3 ubiquitin ligases LRBs physically interact with CRY1 and are also involved in mediating CRY1 ubiquitination and degradation in response to HBL. We further demonstrated that blue-light inhibitor of cryptochromes 1 interacts with CRY1 in a blue-light-dependent manner to inhibit CRY1 dimerization/oligomerization, leading to the repression of HBL-induced degradation of CRY1. Our findings indicate that the regulation of CRY1 stability in HBL is coordinated by COP1 and LRBs, which provides a mechanism by which CRY1 attenuates its own signaling and optimizes photomorphogenesis under HBL.

Community engagement on-site rapid test for chlamydia and gonorrhea among men who have sex with men: a pioneering study in Guangzhou, China.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are prevalent among men who have sex with men (MSM) in China. However, compared to syphilis and HIV, the testing rate for chlamydia and gonorrhea remains low. The purpose of this pilot study was to evaluate the feasibility for conducting rapid nucleic acid test for chlamydia and gonorrhea in MSM community-based organizations (CBO). METHOD: We recruited our participants through an MSM CBO where free HV and syphilis testing were routinely provided. We collected data including social-demographic background, sexual history, chlamydia and gonorrhea testing history, and reasons for accepting this on-site rapid testing. Urine and/or anorectal swab samples were collected and tested for chlamydia and gonorrhea on-site and the testing results were delivered in about 1.5 h. Positive cases received on-site free treatment. RESULTS: From August 2020 to October 2020, 634 MSM visited the CBO for syphilis and HIV testing and 158 (158/634, 24.9%) accepted the on-site chlamydia and gonorrhea rapid test, 135 were finally enrolled. The positive rate fo chlamydia was 16.3% (22/135) and 3.0% (4/135) for gonorrhea, respectively. Only 19.3% participants had previously undergone chlamydia and gonorrhea testing and 68.9% (93/135) participants reported that they had heard of gonorrhea, 47.4% (64/135) had heard of chlamydia. The main reason for testing was "free for charge" (66.2%), followed by "convenient, 'shorter waiting time" (45.2%) and "had high-risk sexual behavior recently" (16.3%). CONCLUSIONS: This pilot study showed that the chlamydia and gonorrhea infection rate remains high among MSM, while the testing rate was low. On-site rapid testing is feasible and potentially preferred by MSM.

The perceptions of sexuality and sexually transmitted diseases (STDs) among adolescent STD patients: A qualitative study.

PURPOSE: To explore the causes and outcomes of sexually transmitted diseases (STDs) in the adolescent STD patients (ASPs) in relation to their access to and interpretation of sexual and STD knowledge, their attitudes towards premarital sex, and their feelings and thoughts after getting STDs. METHODS: A qualitative study was conducted to interview 16 ASPs (12 males, 4 females) using convenience sampling. One-on-one, semi-structured, and confidential interviews were conducted in an outpatient clinic room at a dermatology hospital in Guangzhou, China. Data were analysed via thematic analysis with NVivo 12 software. RESULTS: Four main themes were derived from the data: sex education before getting STDs, cognition of the definition of STDs and their transmission, attitude towards premarital sex, and impact of infection with STDs. Most of the participants had very limited information about sexuality from their families or schools, lacked STD knowledge, and considered premarital sex as normal or common. Infection with STDs had a negative influence on all the participants, especially on female participants, as they felt ashamed and some even did not want to get married in the future. CONCLUSION: Limited sex education, lack of sexual knowledge, and an open attitude towards premarital sex led to STDs among adolescents. This study highlights the importance of providing effective sex education. In addition, specific and targeted health guidance and suggestions should be provided to ASPs to help them deal with STDs and the life experience with STDs objectively and correctly.

Prevalence and correlates of Mycoplasma genitalium infection among patients attending a sexually transmitted infection clinic in Guangdong, China: a cross-sectional study.

BACKGROUND: Mycoplasma genitalium (MG) causes urogenital tract infections and is associated with reproductive morbidity. Although MG has been reported across many regions and population groups, it is not yet routinely tested for in China. Our study contributes to current research by reporting the prevalence and correlates of MG infection in patients attending a sexually transmitted infection (STI) clinic in Guangdong from Jan 2017-May 2018. METHODS: Urethral (from 489 men) and endo-cervical (from 189 women) samples, blood samples, and patient histories (via questionnaires) were collected. Doctors clinically diagnosed anogenital warts (GW) during the examination (n = 678). The presence of MG was evaluated using an in-house via polymerase chain reaction protocol. We also tested all participants for herpes simplex virus-2 (HSV-2), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), syphilis and HIV. Univariate and multivariate logistic regression were used to evaluate factors associated with MG. RESULTS: MG was detected in 7.2% (49/678) of the patients (men, 7.4%; women, 6.9%). The MG positivity rate was 14.2% among symptomatic patients, and 5.6% for asymptomatic patients, respectively. Only 36.7% (18/49) Mg positive patients were symptomatic. Among the MG-infected patients, 10.2% were co-infected with CT, 6.1% with NG, 8.2% with HSV-2, 4.1% with syphilis and 22.4% with GW. Presentation with clinical symptoms was significantly associated with MG infection [OR = 2.52 (2.03-3.13)]. In our analysis, MG was not associated with other STIs. CONCLUSIONS: MG is a relatively common infection among individuals attending an STI clinic in Guangdong Province. Routine testing of symptomatic patients may be necessary, and more epidemiological studies are needed to provide evidence for future testing guidelines.

The transcription factor ZmNAC126 accelerates leaf senescence downstream of the ethylene signalling pathway in maize.

Leaf senescence is an integral part of plant development, during which, nutrients are remobilized from senescent leaves to fast-growing organs. The initiation and progression dynamics of leaf senescence is therefore vital not only to the maximal accumulation of assimilates but also to the efficient remobilization of nutrients. Senescence is a finely tuned process that involves the action of a large number of transcription factors (TFs). The NAC TFs play critical roles in regulating leaf senescence in Arabidopsis, wheat, rice and tomato. Here, we identified a NAC TF, ZmNAC126 that is responsive to leaf senescence in maize. Ectopic overexpression of ZmNAC126 in Arabidopsis and maize enhanced chlorophyll degradation and promoted leaf senescence. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that ZmNAC126 could directly bind to the promoters of major chlorophyll catabolic genes in maize. Dual-luciferase assay in maize protoplasts indicated that ZmNAC126 positively regulates these chlorophyll catabolic genes in maize. Moreover, ZmNAC126 could be induced by ethylene, and ZmEIN3, a major TF of ethylene signalling, could bind to its promoter to transactivate its expression. Taken together, ZmNAC126 may play a pivotal role in regulating natural and ethylene-triggered leaf senescence in maize.

Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at a STI Clinic in Guangzhou, China, 2016-2018.

BACKGROUND: Antimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China. METHODS: A total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA). RESULTS: 98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I). CONCLUSIONS: The high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.

Differences in cadmium accumulation between indica and japonica rice cultivars in the reproductive stage.

Excessive cadmium (Cd) in rice grains is of great concern worldwide, particularly in southern China where heavy metal pollution in the soil is widespread. Much work has been done regarding the key genes responsible for Cd absorption, transport, and accumulation in rice, but little is known about the differences of Cd accumulation between indica and japonica rice cultivars during the reproductive stage. Furthermore, physiological parameters, such as nonstructural carbohydrate content, involved in Cd accumulation have not been fully elucidated. We studied several indica and japonica cultivars under three different Cd treatment levels and harvested them at different periods after heading. Differences in Cd accumulation between subspecies mainly were generated during the reproductive stage. An increase in the Cd pollution level caused the average absorption rate of Cd in the aerial parts of the indica cultivars in the reproductive stage to be 6.17, 4.52, and 3.89 times greater than that of the japonica cultivars across the three Cd treatments. The contribution of Cd absorption by shoots to Cd accumulation at the pre- or postheading stages was 33.8% and 66.2% in indica, and 44.9% and 55.1% in japonica. We found a significant negative correlation between Cd content in the rice grains and the content of nonstructural carbohydrates in the sheath (P < 0.05). Cd translocation from sheath to grain occurred along with sugar transfer in the indica cultivars. The Cd content of the indica cultivar grain was 1.84-4.14 times higher than that of the japonica cultivars (P < 0.05). The japonica cultivars thus met the cereal Cd limits of China (0.2 mg kg-1) under low and moderate soil Cd pollution. These findings are helpful for the selection of proper cultivars and field management practices to alleviate Cd exposure risk in rice production.

Automated breast imaging report generation based on the integration of multiple image features in a metadata format for shared decision-making.

Importance: Medical imaging increases the workload involved in writing reports. Given the lack of a standardized format for reports, reports are not easily used as communication tools. Objective: During medical team-patient communication, the descriptions in reports also need to be understood. Automatically generated imaging reports with rich and understandable information can improve medical quality. Design, setting, and participants: The image analysis theory of Panofsky and Shatford from the perspective of image metadata was used in this study to establish a medical image interpretation template (MIIT) for automated image report generation. Main outcomes and measures: The image information included digital imaging and communications in medicine (DICOM), reporting and data systems (RADSs), and image features used in computer-aided diagnosis (CAD). The utility of the images was evaluated by a questionnaire survey to determine whether the image content could be better understood. Results: In 100 responses, exploratory factor analysis revealed that the factor loadings of the facets were greater than 0.5, indicating construct validity, and the overall Cronbach's alpha was 0.916, indicating reliability. No significant differences were noted according to sex, age or education. Conclusions and relevance: Overall, the results show that MIIT is helpful for understanding the content of medical images.

Association between preconception body mass index and fertility in adult female: A systematic review and meta-analysis.

Obesity potentially reduces fertility, but systematic reviews are lacking to summarize the existing literature. Therefore, we systematically summarized the association between preconception body mass index (BMI) and fertility in adult female based on existing reports. Up to September 2023, we conducted literature retrievals in different databases, including Web of Science, PubMed, Wiley, and ScienceDirect. Finally, 18 studies were included. Female with overweight/obesity (FOR = 0.85; 95% CI: 0.80, 0.90), obesity (FOR = 0.76; 95% CI: 0.69, 0.83), and overweight (FOR = 0.93; 95% CI: 0.88, 0.99) was associated with the significant time-to-pregnancy (TTP) prolongation (reduced fecundability). Interestingly, underweight was moderately associated with prolonged TTP in females (FOR = 0.95; 95% CI: 0.91, 0.99). Female overweight/obesity was associated with an increased risk of subfecundity (OR = 1.44; 95% CI: 1.20, 1.72) and infertility (OR = 1.60, 95% CI: 1.31-1.94). The findings emphasize the importance of considering appropriate preconception BMI at the population level for female fertility outcomes. In particular, prepregnancy obesity in females is strongly associated with prolonged TTP and increased risk of subfecundity. Scientific management of preconception BMI may improve fertility.

Differential responses of the electron transfer capacities of soil humic acid and fulvic acid to long-term wastewater irrigation.

Wastewater irrigation is used to supplement agricultural irrigation because of its benefits and freshwater resource scarcity. However, whether wastewater irrigation for many years affects the electron transfer capacity (ETC) of natural organic matter in soil remains unclear, and organic matter could influence the decomposition and mineralization of substances with redox characteristics in soil through electron transfer, ultimately affecting the soil environment. The composition of soil humic substances (HS) is highly complex, and the effects of soil humic acid (HA) and fulvic acid (FA) on ETC is poorly understood. In this study, we separately evaluated the responses of the electron-accepting capacity (EAC) and electron-donating capacity (EDC) of soil HA and FA in agricultural fields to various durations of wastewater irrigation. Results showed that the EAC of HA and FA increased significantly with increasing the duration of wastewater irrigation. When wastewater irrigation lasted for 56 years, the EAC of HA showed a higher increment (590 %) than that of FA (223 %). The EDC of soil HA and FA, conversely, decreased compared to the control, with the highest reduction of 35.6 % for HA and 65.9 % for FA. Specifically, the EDC of HA gradually decreased starting from 29 years of wastewater irrigation, whereas the decrease in the EDC of FA exhibited no clear pattern in relation to the duration of wastewater irrigation. Increased soil organic matter and total nitrogen content under long-term wastewater irrigation led to an increase in sucrase and phosphatase activities, along with an increase in EAC and a decrease in EDC of HS. This suggests that soil enzyme activities may ultimately lead to changes in ETC. The results of this research provide practical insights into the redox system in soil and its driving role in soil organic matter transformation and nutrient cycling under wastewater irrigation.

MOF-mediated PRDX1 acetylation regulates inflammatory macrophage activation.

Signaling-dependent changes in protein phosphorylation are critical to enable coordination of transcription and metabolism during macrophage activation. However, the role of acetylation in signal transduction during macrophage activation remains obscure. Here, we identify the redox signaling regulator peroxiredoxin 1 (PRDX1) as a substrate of the lysine acetyltransferase MOF. MOF acetylates PRDX1 at lysine 197, preventing hyperoxidation and thus maintaining its activity under stress. PRDX1 K197ac responds to inflammatory signals, decreasing rapidly in mouse macrophages stimulated with bacterial lipopolysaccharides (LPSs) but not with interleukin (IL)-4 or IL-10. The LPS-induced decrease of PRDX1 K197ac elevates cellular hydrogen peroxide accumulation and augments ERK1/2, but not p38 or AKT, phosphorylation. Concomitantly, diminished PRDX1 K197ac stimulates glycolysis, potentiates H3 serine 28 phosphorylation, and ultimately enhances the production of pro-inflammatory mediators such as IL-6. Our work reveals a regulatory role for redox protein acetylation in signal transduction and coordinating metabolic and transcriptional programs during inflammatory macrophage activation.

Prenatal exposure to fenvalerate causes depressive-like behavior in adulthood by inhibiting brain-derived 5-HT synthesis.

The developmental toxicity of fenvalerate, a representative pyrethroid insecticide, is well documented. The present study aimed to explore whether prenatal exposure to fenvalerate causes depression-like behavior in adulthood. Pregnant mice were orally administrated with either corn oil or fenvalerate (2 or 20 mg/kg) during pregnancy. Depressive-like behaviors were assessed by tail suspension test (TST), forced swim test (FST) and sucrose preference test (SPT). Immobility times in TST and FST were increased in offspring whose mothers were exposed to fenvalerate throughout pregnancy. By contrast, sugar preference index, as determined by SPT, was decreased in fenvalerate-exposed offspring. Prefrontal PSD95, a postsynaptic membrane marker, was downregulated in fenvalerate-exposed adulthood offspring. Fenvalerate-induced reduction of prefrontal PSD95 began at GD18 fetal period. Accordingly, prefrontal 5-HT, a neurotransmitter for synaptogenesis, was also reduced in fenvalerate-exposed GD18 fetuses. Tryptophan hydroxylase 2 (TPH2), a key enzyme for 5-HT synthesis, was downregulated in the midbrain of fenvalerate-exposed GD18 fetuses. Additional experiment showed that GRP78 and p-eIF2α, two endoplasmic reticulum stress-related proteins, were increased in the midbrain of fenvalerate-exposed fetal mice. The present results suggest that prenatal exposure to fenvalerate causes depressive-like behavior in adulthood, partially by inhibiting brain-derived 5-HT synthesis.

Pricing and Quantity Decisions under Asymmetric Carbon Emission Reduction Information and Cap-and-Trade Mechanism.

With the continuous spread of cap-and-trade mechanisms and consumers' great concerns about environmental issues, manufacturers strive to reduce carbon emissions. Unfortunately, they are not always willing to disclose their accurate emission reductions or may even falsify emission reduction information. By developing a signaling model, we explore the impact of the cap-and-trade mechanism and asymmetric information on the decision-making of supply chain members composed of a manufacturer regulated by the cap-and-trade mechanism, and a retailer. As a result, we show that the low-type manufacturer has the incentive to mimic the pricing behavior of the high-type manufacturer under information asymmetry. Thus, in order to avoid this mimicry, the high-type manufacturer will distort the wholesale price. Moreover, the impact of the cap-and-trade mechanism on the manufacturer depends on the initial quotas. Only when the initial quota is in the middle range does the high-type manufacturer benefit, while the low-type manufacturer suffers. Furthermore, the low-type manufacturer tends to hide emission reduction information, while the high-type manufacturer tends to disclose the information. We also address how information asymmetry weakens the emission reduction advantages of the high-type manufacturer. However, the cap-and-trade mechanism can effectively alleviate this negative effect.

Experimental study on the galloping characteristics of single ice-coated transmission lines under oblique flows.

Galloping of ice-coated transmission lines is occasionally observed under oblique wind directions. However, most current investigations on the galloping mechanisms are for flow perpendicular to the span of the transmission lines. In order to address this gap, this research studies the galloping characteristics of ice-coated transmission lines under oblique flows based on wind tunnel tests. The wind-induced displacement of an aero-elastic iced-coated transmission line model was measured with a noncontact displacement measurement equipment in a wind tunnel at different wind speeds and directions. The results show that galloping is characterized by elliptical trajectories and negative damping, which is more likely to occur under oblique flows than the direct flow (0°). At 15° wind direction, a galloping in vertical direction was observed at wind speeds above 5 m/s. At 30° wind direction, galloping was observed over the entire range of the tested wind speeds. Moreover, the galloping amplitudes under oblique flows are observed to be larger than that at the direct flows. Consequently, when the wind direction between the major winter monsoon azimuth and the lateral direction of transmission line route is between 15° and 30°, appropriate anti-galloping devices are highly recommended in practice.

Efficacy and safety of the innovative monoclonal antibodies in adults with generalized myasthenia gravis: a Bayesian network analysis.

Background: A series of clinical trials support the effectiveness of monoclonal antibodies for generalized myasthenia gravis (MG) compared to the placebo, but the priority among drugs remains unclear. Therefore, we conduct a frequentist network meta-analysis (NMA) to compare the relative effects of different drugs for generalized MG. Methods: PubMed, Embase, Cochrane Library, and clinicaltrials.gov were systematically searched for eligible studies up to 1 June 2023. The primary outcome was efficacy (Myasthenia Gravis Activities of Daily Living [MG-ADL] score and Quantitative Myasthenia Gravis [QMG] score) and safety (adverse events [AEs]). Mean difference (MD) and risk ratio (RR) with their 95% credible intervals (95%CrIs) were used to show the effect size of continuous and categorical variables, respectively. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Thirteen studies involving 1167 individuals were identified for NMA. For efficacy outcomes, belimumab, efgartigimod, mezagitamab 600mg, and nipocalimab 60mg/kg were inferior to rozanolixzumab 7mg/kg (MD ranged from 2 to 3.69) and rozanolixzumab 10mg/kg (MD ranged from 2.04 to 3.72) in MG-ADL score, and rozanolixzumab had the highest rank probability (83%) according to the subjective surface under the curve ranking area (SUCRA). For QMG score, batoclimab 340mg (MD ranged from 4.32 to 8.52) and batoclimab 680mg (MD ranged from 4.11 to 9.31) were more effective than placebo and other monoclonal antibodies except for rozanolixzumab, with the highest SUCRA value (93% and 97% respectively). For safety outcomes, belimumab achieved the highest SUCRA value (89.8%) with significant statistical difference compared to rozanolixzumab 7mg/kg (RR 0.08, 95%CrI 0.01 to 0.94) and rozanolixzumab 10mg/kg (RR 0.08, 95%CrI 0.01 to 0.86). Conclusion: While all monoclonal antibodies were superior to the placebo, rozanolixzumab and batoclimab might be the most effective for generalized MG. However, rozanolixzumab was associated with higher incidence of AEs. Given the limitations inherent in indirect comparisons, further head-to-head and extensive observational studies are necessary to confirm our findings. Systematic review registration: https://inplasy.com/?s=202370112, identifier 202370112.