Genomic anatomy of homozygous XX females and YY males reveals early evolutionary trajectory of sex-determining gene and sex chromosomes in Silurus fishes.

Sex chromosomes display remarkable diversity and variability among vertebrates. Compared with research on the X/Y and Z/W chromosomes, which have long evolutionary histories in mammals and birds, studies on the sex chromosomes at early evolutionary stages are limited. Here, we precisely assembled the genomes of homozygous XX female and YY male Lanzhou catfish (Silurus lanzhouensis) derived from an artificial gynogenetic family and a self-fertilized family, respectively. Chromosome 24 (Chr24) was identified as the sex chromosome based on resequencing data. Comparative analysis of the X and Y chromosomes showed an approximate 320 kb Y-specific region with a Y-specific duplicate of anti-Mullerian hormone type-II receptor (amhr2y), which is consistent with findings in two other Silurus species but on different chromosomes (Chr24 of S. meridionalis and Chr5 of S. asotus). Deficiency of amhr2y resulted in male-to-female sex reversal, indicating that amhr2y plays a male-determining role in S. lanzhouensis. Phylogenetic analysis and comparative genomics revealed that the common sex-determining gene amhr2y was initially translocated to Chr24 of the Silurus ancestor along with the expansion of transposable elements. Chr24 was maintained as the sex chromosome in S. meridionalis and S. lanzhouensis, whereas a sex-determining region transition triggered sex chromosome turnover from Chr24 to Chr5 in S. asotus. Additionally, gene duplication, translocation, and degeneration were observed in the Y-specific regions of Silurus species. These findings present a clear case for the early evolutionary trajectory of sex chromosomes, including sex-determining gene origin, repeat sequence expansion, gene gathering and degeneration in sex-determining region, and sex chromosome turnover.

Chandipura viral glycoprotein (CNV-G) promotes Gectosome generation and enables delivery of intracellular therapeutics.

Overexpression of vesicular stomatitis virus G protein (VSV-G) elevates the secretion of EVs known as gectosomes, which contain VSV-G. Such vesicles can be engineered to deliver therapeutic macromolecules. We investigated viral glycoproteins from several viruses for their potential in gectosome production and intracellular cargo delivery. Expression of the viral glycoprotein (viral glycoprotein from the Chandipura virus [CNV-G]) from the human neurotropic pathogen Chandipura virus in 293T cells significantly augments the production of CNV-G-containing gectosomes. In comparison with VSV-G gectosomes, CNV-G gectosomes exhibit heightened selectivity toward specific cell types, including primary cells and tumor cell lines. Consistent with the differential tropism between CNV-G and VSV-G gectosomes, cellular entry of CNV-G gectosome is independent of the Low-density lipoprotein receptor, which is essential for VSV-G entry, and shows varying sensitivity to pharmacological modulators. CNV-G gectosomes efficiently deliver diverse intracellular cargos for genomic modification or responses to stimuli in vitro and in the brain of mice in vivo utilizing a split GFP and chemical-induced dimerization system. Pharmacokinetics and biodistribution analyses support CNV-G gectosomes as a versatile platform for delivering macromolecular therapeutics intracellularly.

Enhanced poly-γ-glutamic acid synthesis in Corynebacterium glutamicum by reconstituting PgsBCA complex and fermentation optimization.

Previously, a novel Corynebacterium glutamicum strain for the de novo biosynthesis of tailored poly-γ-glutamic acid (γ-PGA) has been constructed by our group. The strain was based on the γ-PGA synthetase complex, PgsBCA, which is the only polyprotein complex responsible for γ-PGA synthesis in Bacillus spp. In the present study, PgsBCA was reconstituted and overexpressed in C. glutamicum to further enhance γ-PGA synthesis. First, we confirmed that all the components (PgsB, PgsC, and PgsA) of γ-PGA synthetase derived from B. licheniformis are necessary for γ-PGA synthesis, and γ-PGA was detected only when PgsB, PgsC, and PgsA were expressed in combination in C. glutamicum. Next, the expression level of each pgsB, pgsC, and pgsA was tuned in order to explore the effect of expression of each of the γ-PGA synthetase subunits on γ-PGA production. Results showed that increasing the transcription levels of pgsB or pgsC and maintaining a medium-level transcription level of pgsA led to 35.44% and 76.53% increase in γ-PGA yield (γ-PGA yield-to-biomass), respectively. Notably, the expression level of pgsC had the greatest influence (accounting for 68.24%) on γ-PGA synthesis, followed by pgsB. Next, genes encoding for PgsC from four different sources (Bacillus subtilis, Bacillus anthracis, Bacillus methylotrophicus, and Bacillus amyloliquefaciens) were tested in order to identify the influence of PgsC-encoding orthologues on γ-PGA production, but results showed that in all cases the synthesis of γ-PGA was significantly inhibited. Similarly, we also explored the influence of gene orthologues encoding for PgsB on γ-PGA production, and found that the titer increased to 17.14 ± 0.62 g/L from 8.24 ± 0.10 g/L when PgsB derived from B. methylotrophicus replaced PgsB alone in PgsBCA from B. licheniformis. The resulting strain was chosen for further optimization, and we achieved a γ-PGA titer of 38.26 g/L in a 5 L fermentor by optimizing dissolved oxygen level. Subsequently, by supplementing glucose, γ-PGA titer increased to 50.2 g/L at 48 h. To the best of our knowledge, this study achieved the highest titer for de novo production of γ-PGA from glucose, without addition of L-glutamic acid, resulting in a novel strategy for enhancing γ-PGA production.

Non-invasive imaging using a low-spatial-coherence multimode random polymer fiber laser.

Random lasers (RLs), with their low spatial coherence, are ideal illumination sources for speckle-free imaging. However, it is still challenging for RLs to maintain low spatial coherence with the need for integration and directionality. Here, a disordered multimode random polymer fiber laser (RPFL) is proposed and implemented as a low-spatial-coherence light source. Compared to typical multimode optical fibers, the number of accommodated modes is increased by about 11×, the speckle contrast is reduced to 0.013, and the spatial coherence factor is reduced to 0.08. The low-spatial-coherence property enables RPFL to produce significantly superior imaging quality in both speckle-free imaging and non-invasive imaging through opacity. This study provides a strategy for an integrated speckle-free imaging system and paves the way for non-invasive imaging.

Conformationally constrained potent inhibitors for enhancer of zeste homolog 2 (EZH2).

The enhancer of zeste homolog 2 (EZH2) plays the role of the main catalytic subunit of polycomb repressive complex 2 (PRC2) that catalyzes the methylation of histone H3 lysine 27 (H3K27). Overexpression or mutation of EZH2 has been observed in many types of hematologic malignancies and solid tumors, such as myeloma, lymphoma, prostate, breast, kidney, and lung cancers. EZH2 has been demonstrated as a promising therapeutic target for the treatment of tumors. Based on the structure of 1 (EPZ-6438), a series of novel conformationally constrained derivatives were designed and synthesized aiming to improve the EZH2 inhibition activity, especially for mutated EZH2. Structure and activity relationship (SAR) exploration and optimization at both enzymatic and cellular levels led to the discovery of 28. In vitro, 28 displayed potent EZH2 inhibition activity with an IC50 value of 0.95 nM, which is comparable to EPZ-6438 (1). 28 exhibited high anti-proliferation activity against different lymphoma cell lines including WSU-DLCL2, Pfeiffer and Karpas-422 (IC50 = 2.36, 1.73, and 1.82 nM, respectively). In vivo, 28 showed acceptable pharmacokinetic characteristics (oral bioavailability F = 36.9%) and better efficacy than 1 in both Pfeiffer and Karpas-422 xenograft mouse models, suggesting that it can be further developed as a potential therapeutic candidate for EZH2-associated cancers.

Association between body stature with ocular biometrics and refraction among Chinese preschoolers.

PURPOSE: To evaluate the association of body stature with ocular biometrics and refraction in preschool children. METHODS: A cross-sectional, school-based study was conducted in Shenzhen, China. Preschool children aged 3 to 6 from 10 randomly-selected kindergartens were recruited. Ocular biometric parameters, including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD), corneal radius curvature (CR), axial length to corneal radius ratio (AL-to-CR ratio) and lens thickness (LT) were measured using non-contact partial-coherence laser interferometry. Cycloplegic refractions were obtained by a desktop autorefractor. Body height and weight were measured using standard procedures. The association between body stature and ocular biometrics were analyzed with univariable and multivariable regression model. RESULTS: A total of 373 preschoolers were included. AL, ACD, VCD, CR, and AL-to-CR ratio, were positively associated with height and weight (p < 0.05), whereas LT was negatively associated with height and weight (p < 0.01). No association was observed between stature and central cornea thickness and refraction. After adjusted for age and gender in a multivariable regression model, AL had positive associations with height (p < 0.01) and weight (p < 0.01). However, refraction had no significant association with stature parameters. CONCLUSION: Taller and heavier preschoolers had eyes with longer AL, deeper vitreous chamber, and flatter cornea. The significant associations between body stature and ocular biometric parameters reveal the driving influence of body development on the growth of eyeballs in preschoolers.

RACK1 promotes the occurrence and progression of cervical carcinoma.

BACKGROUND: RACK1 has been identified as a multifunctional cytosolic protein, and plays a pivotal role in multiple biological responses involved in several kinds of tumors, while its effect in cervical cancer has not been well elucidated yet. The study aimed to investigate the role of RACK1 in cervical cancer occurrence and progression. METHODS: The expression of RACK1 in cervical specimens was measured by immunohistochemical staining and Western blot assay. Transgenic mice were used to detect the role of RACK1 in modulating tumorigenesis in vivo. Cervical carcinoma cell lines were used to explore the underlying mechanisms of RACK1 on the behaviors of tumor cells in vitro. RESULTS: We found that RACK1 expression was upregulated in cancer tissues compared with adjacent tissues, and its expression was gradually increased from cervictis, and cervical intraepithelial neoplasis (CIN) to carcinoma. Genetic overexpression of RACK1 facilitated tumor formation and growth in nude mice. Mechanism studies disclosed that RACK1 over-expression prolonged the G0 /G1 phase by up-regulating the expression of cyclinD1, down-regulating p21 and p27 probably by modulating the phosphorylation of AKT. CONCLUSIONS: Taken together, we concluded that RACK1 stimulates tumorigenesis and progression of cervical cancer via modulating the proliferation of tumor cells, implying that targeting RACK1 may serve as a promising method for cervical cancer therapy.

A Deep Learning Model for Detecting Rhegmatogenous Retinal Detachment Using Ophthalmologic Ultrasound Images.

INTRODUCTION: Rhegmatogenous retinal detachment (RRD) is one of the most common fundus diseases. Many rural areas of China have few ophthalmologists, and ophthalmologic ultrasound examination is of great significance for remote diagnosis of RRD. Therefore, this study aimed to develop and evaluate a deep learning (DL) model, to be used for automated RRD diagnosis based on ophthalmologic ultrasound images, in order to support timely diagnosis of RRD in rural and remote areas. METHODS: A total of 6,000 ophthalmologic ultrasound images from 1,645 participants were used to train and verify the DL model. A total of 5,000 images were used for training and validating DL models, and an independent testing set of 1,000 images was used to test the performance of eight DL models trained using four different DL model architectures (fully connected neural network, LeNet5, AlexNet, and VGG16) and two preprocessing techniques (original, original image augmented). Receiver operating characteristic (ROC) curves were used to analyze their performance. Heatmaps were generated to visualize the process of the best DL model in the identification of RRD. Finally, five ophthalmologists were invited to diagnose RRD independently on the same test set of 1,000 images for performance comparison with the best DL model. RESULTS: The best DL model for identifying RRD achieved an area under the ROC curve (AUC) of 0.998 with a sensitivity and specificity of 99.2% and 99.8%, respectively. The best preprocessing method in each model architecture was the application of original image augmentation (average AUC = 0.982). The best model architecture in each preprocessing method was VGG16 (average AUC = 0.998). CONCLUSION: The best DL model determined in this study has higher accuracy, sensitivity, and specificity than the ophthalmologists' diagnosis in identifying RRD based on ophthalmologic ultrasound images. This model may provide support for timely diagnosis in locations without access to ophthalmologic care.

[A design of interactive review for computer aided diagnosis of pulmonary nodules based on active learning].

Automatic detection of pulmonary nodule based on computer tomography (CT) images can significantly improve the diagnosis and treatment of lung cancer. However, there is a lack of effective interactive tools to record the marked results of radiologists in real time and feed them back to the algorithm model for iterative optimization. This paper designed and developed an online interactive review system supporting the assisted diagnosis of lung nodules in CT images. Lung nodules were detected by the preset model and presented to doctors, who marked or corrected the lung nodules detected by the system with their professional knowledge, and then iteratively optimized the AI model with active learning strategy according to the marked results of radiologists to continuously improve the accuracy of the model. The subset 5-9 dataset of the lung nodule analysis 2016(LUNA16) was used for iteration experiments. The precision, F1-score and MioU indexes were steadily improved with the increase of the number of iterations, and the precision increased from 0.213 9 to 0.565 6. The results in this paper show that the system not only uses deep segmentation model to assist radiologists, but also optimizes the model by using radiologists' feedback information to the maximum extent, iteratively improving the accuracy of the model and better assisting radiologists.

Leonuride protects diabetic nephropathy by activating SREBPs pathway.

Diabetic nephropathy (DN), a micro vascular complication of diabetes, is the main cause of end-stage renal disease, with a morbidity over 40% of diabetes. High glucose and lipid metabolism dysfunction are the leading cause of the development of DN. Previous study demonstrated that increased expression or activation of SREBPs in models of DN. Leonuride (LE), as an active constituent of Leonurus japonicus Houttuyn, has multiple biological activities, including antioxidant and anti-inflammatory effects. Previous studies showed that increasing the degradation of mature SREBPs is a robust way of lowering lipids and improve lipid metabolism dysfunction. However, effective regulation method of SREBPs degradation are still lacking. Herein, this study indicated that LE can effectively improve glucose and lipid metabolism disorders. In addition, the kidney function was also improved by inhibition of SREBPs activities in streptozocin (STZ)-induced type II diabetic mice. To our knowledge, this is the first time to describe the detailed mechanism of LE on the inhibition of precursor SREBPs, which would present a new direction for diabetic nephropathy treatment.

SUMO-specific proteases: SENPs in oxidative stress-related signaling and diseases.

Oxidative stress is employed to depict a series of responses detrimental to normal cellular functions resulting from an imbalance between intracellular oxidants, mainly reactive oxygen species and antioxidant defenses. Oxidative stress often contributes to the development of various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. In this process, the relationship between small ubiquitin-like modifier (SUMO) and oxidative stress has garnered significant attention, with its posttranslational modification (PTM) frequently serving as a marker of oxidative stress status. Sentrin/SUMO-specific proteases (SENPs), affected by alternative splicing, PTMs such as phosphorylation and ubiquitination, and various protein interactions, are crucial molecules in the SUMO process. The human SENP family has six members (SENP1-3, SENP5-7), which are classified into two categories based on sequence similarity, substrate specificity, and subcellular location. They have two core functions in the human body: first, by cleaving the precursor SUMO and exposing the C-terminal glycine, they initiate the SUMO process; second, they can specifically recognize and dissociate SUMO proteins bound to substrates, a process known as deSUMOylation. However, the connection between deSUMOylation and oxidative stress remains a relatively unexplored area despite their strong association with oxidative diseases such as cancer and cardiovascular disease. This article aims to illustrate the significant contribution of SENPs to the oxidative stress pathway through deSUMOylation by reviewing their structure and classification, their roles in oxidative stress, and the changes in their expression and activity in several typical oxidative stress-related diseases.

How to incorporate new agents into precise medicine for cholangiocarcinoma?

Cholangiocarcinoma, a rare and aggressive form of cancer originating from the bile ducts in the liver, poses a significant challenge for treatment. However, the emergence of precision medicine has brought newfound hope for more effective therapies. Several precision medicine approaches have demonstrated promise in the treatment of cholangiocarcinoma. One such approach is targeted therapy, which involves utilizing drugs that specifically target the genetic mutations or alterations present in the tumor cells. In the case of cholangiocarcinoma, mutations in the IDH1 and IDH2 genes are frequently observed. Immunotherapy is another precision medicine approach being explored for the treatment of cholangiocarcinoma. Immune checkpoint inhibitors like pembrolizumab and nivolumab can be used to bolster the body's immune response against cancer cells. While the response to immunotherapy can vary among individuals, studies have shown promising results, particularly in patients with high levels of tumor-infiltrating lymphocytes or microsatellite instability. Moreover, molecular profiling of cholangiocarcinoma tumors can play a crucial role in identifying potential targets for precision medicine. Through advanced next-generation sequencing techniques, specific gene alterations or dysregulations in pathways can be identified, potentially guiding treatment decisions. This personalized approach enables tailored treatment plans based on the unique genetic characteristics of each patient's tumor. In conclusion, the advent of precision medicine has opened up new avenues for the treatment of cholangiocarcinoma. Targeted therapy and immunotherapy have exhibited promising results, and further molecular profiling is expected to uncover additional therapeutic options. Such advancements represent a significant step forward in the quest to enhance outcomes for individuals affected by cholangiocarcinoma.

The Effect of a Video-Assisted Health Education Program Followed by Peer Education on the Health Literacy of COVID-19 and Other Infectious Diseases Among School Children: Quasi-Randomized Controlled Trial.

BACKGROUND: To improve the engagement and effectiveness of traditional health programs, it is necessary to explore alternative models of health education including video-assisted lectures and peer education. OBJECTIVE: This study aimed to evaluate the effects of a combination of video-assisted lectures and peer education on health literacy related to infectious diseases among students. METHODS: Third-grade classes from 11 pilot schools in Longgang District of Shenzhen, China, were randomized to the intervention and control groups. In the intervention group, a video-assisted interactive health education program was conducted twice over a time span of 5 months. Each of the 2 sessions included a 40-minute lecture on COVID-19 and other common infectious diseases in schools and a 5-minute science video. In addition, 5 "little health supervisors" at the end of the first session were elected in each class, who were responsible for helping class members to learn health knowledge and develop good hygiene habits. Students answered the same quiz before the first and after the second session. Models based on item response theory (IRT) were constructed to score the students' knowledge of infectious diseases based on the quiz. RESULTS: In total, 52 classes and 2526 students (intervention group: n=1311; control group: n=1215) were enrolled. Responses of the baseline survey were available for 2177 (86.2%; intervention group: n=1306; control group: n=871) students and those of the postintervention survey were available for 1862 (73.7%; intervention group: n=1187; control group: n=675). There were significant cross-group differences in the rates of correctly answering questions about influenza symptoms, transmission, and preventive measures; chicken pox symptoms; norovirus diarrhea symptoms; mumps symptoms; and COVID-19 symptoms. Average IRT scores of questions related to infectious diseases in the intervention and control groups were, respectively, -0.0375 (SD 0.7784) and 0.0477 (SD 0.7481) before the intervention (P=.01), suggesting better baseline knowledge in the control group. After the intervention, the average scores of the intervention and control groups were 0.0543 (SD 0.7569) and -0.1115 (SD 0.7307), respectively (P<.001), suggesting not only significantly better scores but also greater improvement in the intervention group. CONCLUSIONS: After the health education project, the correct answer rate of infectious disease questions in the intervention group was higher than that of the control group, which indicates significant effects of the combination of video-assisted lectures and peer education for the promotion of health literacy. In addition, the intervention effect of the first session persisted for at least 4 months up to the second session. As such, the proposed program was effective in improving the health literacy of school children in relation to infectious diseases and should be considered for massive health promotion campaigns during pandemics. TRIAL REGISTRATION: ISRCTN ISRCTN49297995; https://www.isrctn.com/ISRCTN49297995.

N-doped carbon layer cladded carbon sphere for broadband and boosted microwave attenuation capacity.

Structural construction and heteroatom doping are deemed effective strategies for designing a high-performance microwave absorbing composite to eliminate electromagnetic hazards. Herein, a series of core-shell structural carbon@N-doped carbon (C@NC) nanospheres were successfully fabricated without employing additional modifying agents and sophisticated operation. After incorporating them into a polyvinylidene fluoride (PVDF) matrix, the C@NC/PVDF composites possess tunable wave attenuation capacity obtained by regulating the coating layer thickness and filler loading. Benefitting from the design strategy of the core-shell structure and N-doped C, the C@NC-2/PVDF composites displayed the broadest effective absorption bandwidth of 6.29 GHz (11.71-18 GHz) under a filler content of only 10 wt% at 2.01 mm. Additionally, the minimum reflection loss value of C@NC-3/PVDF composites achieves -62.87 dB within the same mass ratio at a thickness of 2.35 mm. The excellent wave dissipation ability is attributed to the combination of optimized impedance matching and synergistically enhanced multiple loss mechanisms including conduction loss, interfacial polarization as well as dipolar polarization. This work offers a ponderable paradigm for the deeper exploitation of high-efficiency carbon absorbers.

Effect of Pelvic Floor Function Exercises Based on the ERAS Concept on Lower Urinary Tract Symptoms after Radical Hysterectomy for Cervical Cancer: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to analyse the effect of pelvic floor function exercises based on the enhanced recovery after surgery (ERAS) concept on lower urinary tract symptoms after radical hysterectomy for cervical cancer. METHODS: The retrospective study was conducted using clinical data of patients admitted to our hospital from January 2021 to December 2022 and underwent radical hysterectomy for cervical cancer. In accordance with the nursing method, the patients were divided into the routine group (conventional care) and the ERAS pelvic floor function exercise group, for which ERAS concept-based pelvic floor function exercises were carried out on the basis of the former group. The confounders between the two groups were matched by propensity score, and the scores of urination, pelvic floor muscle strength, lower urinary tract symptoms and quality of life (QoL) were compared between the two groups after matching. RESULTS: A total of 180 patients were included in the study, of whom 60 patients were identified after propensity score matching, consisting of 30 patients each in the ERAS and routine groups. The baseline characteristics of the two groups were balanced, and the difference was not statistically significant (p > 0.05). Compared with the routine group, the observation group showed significantly shorter first spontaneous urination time, greater first urination volume (p < 0.05), better pelvic floor muscle strength, considerably lower urinary tract symptoms and better QoL at discharge and 3 months after discharge (p < 0.05). CONCLUSIONS: Pelvic floor function exercises based on the ERAS concept can relieve lower urinary tract symptoms, accelerate urination and improve pelvic floor muscle strength and QoL after radical hysterectomy for cervical cancer.

Boosting antitumor efficacy of nanoparticles by modulating tumor mechanical microenvironment.

Nanoparticles have shown great potential for tumor targeting delivery via enhanced permeability and retention effect. However, the tumor mechanical microenvironment, characterized by dense extracellular matrix (ECM), high tumor stiffness and solid stress, leads to only 0.7% of administered dose accumulating in solid tumors and even fewer (∼0.0014%) reaching tumor cells, limiting the therapeutic efficacy of nanoparticles. Furthermore, the tumor mechanical microenvironment can regulate tumor cell stemness, promote tumor invasion, metastasis and reduce treatment efficacy. In this review, methods detecting the mechanical are introduced. Strategies for modulating the mechanical microenvironment including elimination of dense ECM by physical, chemical and biological methods, disruption of ECM formation, depletion or inhibition of cancer-associated fibroblasts, are then summarized. Finally, prospects and challenges for further clinical applications of mechano-modulating strategies to enhance the therapeutic efficacy of nanomedicines are discussed. This review may provide guidance for the rational design and application of nanoparticles in clinical settings.

Safety profiles of Tetracycline-class drugs: a pharmacovigilance analysis of the FAERS database.

BACKGROUND: As synthesis technology advances, novel and efficient derivatives of tetracyclines are found. Three new antibiotics, tigecycline, omadacycline, and eravacycline, approved within the past 18 years, and represent a new era in the use of tetracyclines. To gain further insight into adverse events linked to tetracyclines and better protect pediatric patients, ongoing monitoring of safety data is crucial. METHODS: The FAERS data from the first quarter of 2004 to the third quarter of 2023 in the AERSMine were extracted to conduct disproportionality analysis. The association between five tetracyclines and adverse events was evaluated using reporting odds ratio, and their risk factors were explored by multivariate logistic regression analysis. RESULTS: Our study showed that endocrine disorders had the strongest signal in children, especially thyroid gland disorders. Patients aged 12-18 and treatment with minocycline are risk factors for thyroid adverse events(12-18: OR = 10.727 [7.113-16.177], p < 0.0001; minocycline: OR = 17.025 [10.475-27.678], p < 0.0001).Second-generation tetracycline and third-generation tetracycline ADR patterns differed. Blood fibrinogen decreased and hypofibrinogenaemia were primarily reported with tigecycline and eravacycline. CONCLUSION: The potential effect of minocycline on thyroid function in adolescents should be of concern. This study investigated adverse events highly associated with tetracyclines treatment, which provided basic evidence for further research on tetracyclines-related adverse events for children. However, the safety of third-generation tetracycline in children requires additional validation through a large-scale prospective study.

Evaluation of stripe rust resistance and genome-wide association study in wheat varieties derived from the International Center for Agricultural Research in the Dry Areas.

159 wheat varieties obtained from ICARDA, CYR32, CYR33 and CYR34 were used to evaluate the stripe rust resistance in this study. Seedling resistance was carried out in the green house at the two-leaf stage. Adult-plant resistance was carried out between 2022 and 2023 in Xining and Guide, respectively. A total of 24,151 high-quality SNP loci were obtained from a 55K SNP chip data. Genome-wide association study was carried out between SNP loci and stripe rust resistance. Seedling resistance screening revealed that 91.8% (146) of wheat varieties were resistant to CYR32 and CYR33, while only 49.7% (79) of wheat varieties were resistant to CYR34. Adult-plant resistance showed 153 (96.2%) germplasms represented resistance in 2022, while only 85 (53.4%) showed resistance in 2023. An association study using the 55K SNP chip data results combined with disease ratings of 159 materials at both the seedling and adult stages discovered 593 loci related to stripe rust resistance (P ≤ 0.0001). These loci exhibited contribution rates ranging from 11.1% to 18.7%. Among them, 71 were significantly related to resistance against CYR32 at the seedling stage, with a contribution rate of 12.7%-17.2%. Constituting the vast majority, 518 loci distributed across 21 chromosomes were significantly related to CYR33 at the seedling stage, with a contribution rate of 12.6%-18.7%. Fewer loci were found to be associated with disease resistance in adult plants. In E1 environment, a sole locus was detected on chromosome 2B with a contribution rate of 14.4%. In E2 environment, however, exhibited three loci across chromosomes 2B, 4A, and 7B with contribution rates ranging from 11.1% to 16.9%. A total of 68 multi-effect loci were significantly related to resistance against both CYR32 and CYR33 at the seedling stage, and one stable locus was significantly associated with stripe rust resistance at the adult plant stage.

Effects of nitrogen fertilization combined with subsurface irrigation on alfalfa yield, water and nitrogen use efficiency, quality, and economic benefits.

Proper water and fertilizer management strategies are essential for alfalfa cultivation in arid areas. However, at present, the optimal amounts of subsurface irrigation and nitrogen (N) supply for alfalfa (Medicago sativa L.) cultivation are still unclear. Therefore, a field experiment was conducted in 2022 in Yinchuan, Ningxia, China, to explore the effects of different subsurface irrigation levels (W1, 50% of ETC (crop evapotranspiration); W2, 75% of ETC; W3, 100% of ETC) and N application rates (N0, 0 kg/ha; N1, 75 kg/ha; N2, 150 kg/ha; N3, 225 kg/ha; N4, 300 kg/ha) on alfalfa yield, crop water productivity (CWP), N use efficiency (NUE), quality, and economic benefits. Besides, the least squares method and multiple regression analysis were used to explore the optimal water and N combination for alfalfa cultivation under subsurface irrigation. The results showed that the alfalfa yield, crude ash content, and partial factor productivity from applied N (PFPN) were the highest under W2 level, but there was no difference in PFPN compared with that under W3 level. The branch number (BN), leaf area index (LAI), yield, CWP, irrigation water productivity (IWP), crude protein content (CPC), and economic benefits increased and then decreased with the increase of N application rate, reaching a maximum at the N2 or N3 level, while the NUE and PFPN decreased with the increase of N application rate. Considering the yield, CWP, NUE, quality, and economic benefits, W2N2 treatment was the optimal for alfalfa cultivation under subsurface irrigation. Besides, when the irrigation volume and N application rate were 69.8 ~ 88.7% of ETC and 145 ~ 190 kg/ha, respectively (confidence interval: 85%), the yield, CPC, and economic benefits reached more than 85% of the maximum. This study will provide technique reference for the water and N management in alfalfa cultivation in Northwest China.

[Retracted] microRNA­146b promotes neuroblastoma cell growth through targeting NUMB.

[This retracts the article DOI: 10.3892/etm.2020.8623.].