A rapid, equipment-free method for detecting avirulence genes of Pyricularia oryzae using a lateral flow strip-based RPA assay.

Rice blast, caused by Pyricularia oryzae, is one of the most destructive rice diseases worldwide. Using resistant rice varieties is the most cost-effective way to control rice blast. Consequently, it is critical to monitor the distribution frequency of avirulence genes in rice planting field to facilitate the breedings of resistant rice varieties. In this study, we established a rapid RPA-LFD detection system for the identification of AvrPik, Avr-Piz-t and Avr-Pi9. The optimized reaction temperature and duration were 37°C and 20 min, indicating that the reaction system could be initiated by body temperature without relying on any precision instruments. Specificity analysis showed that the primer and probe combinations targeting three Avr genes exhibited a remarkable specificity for at genus-level detection. Under the optimized condition, the lower detected thresholds of AvrPik, Avr-Piz-t and Avr-Pi9 were 10 fg/µl, 100 fg/µl and 10 pg/µl, respectively. Notably, the detection sensitivity of three Avr genes was much higher than that of PCR. In addition, we also successfully detected the presence of AvrPik, Avr-Piz-t and Avr-Pi9 in the leaf and panicle blast lesions with the RPA-LFD detection system. In particular, the genomic DNA was extracted using the simpler PEG-NaOH rapid extraction method. In summary, we developed the RPA detection system for AvrPik, Avr-Pi9 and Avr-Piz-t, combined with the PEG-NaOH rapid DNA extraction method. The innovative approach achieved rapid, real-time and accurate detection of three Avr genes in the field, which is helpful to understand the distribution frequency of the three Avr genes in the field and provide theoretical reference for the scientific layout of rice resistant varieties.

Cross-domain pedestrian detection via feature alignment and image quality assessment.

Datasets collected under different sensors, viewpoints, or weather conditions cause different domains. Models trained on domain A applied to tasks of domain B result in low performance. To overcome the domain shift, we propose an unsupervised pedestrian detection method that utilizes CycleGAN to establish an intermediate domain and transform a large gap domain-shift problem into two feature alignment subtasks with small gaps. The intermediate domain trained with labels from domain A, after two rounds of feature alignment using adversarial learning, can facilitate effective detection in domain B. To further enhance the training quality of intermediate domain models, Image Quality Assessment (IQA) is incorporated. The experimental results evaluated on Citypersons, KITTI, and BDD100K show that MR of 24.58%, 33.66%, 28.27%, and 28.25% were achieved in four cross-domain scenarios. Compared with typical pedestrian detection models, our proposed method can better overcome the domain-shift problem and achieve competitive results.

The Ras GTPase-activating protein UvGap1 orchestrates conidiogenesis and pathogenesis in the rice false smut fungus Ustilaginoidea virens.

Ras GTPase-activating proteins (Ras GAPs) act as negative regulators for Ras proteins and are involved in various signalling processes that influence cellular functions. Here, the function of four Ras GAPs, UvGap1 to UvGap4, was identified and analysed in Ustilaginoidea virens, the causal agent of rice false smut disease. Disruption of UvGAP1 or UvGAP2 resulted in reduced mycelial growth and an increased percentage of larger or dumbbell-shaped conidia. Notably, the mutant ΔUvgap1 completely lost its pathogenicity. Compared to the wild-type strain, the mutants ΔUvgap1, ΔUvgap2 and ΔUvgap3 exhibited reduced tolerance to H2 O2 oxidative stress. In particular, the ΔUvgap1 mutant was barely able to grow on the H2 O2 plate, and UvGAP1 was found to influence the expression level of genes involved in reactive oxygen species synthesis and scavenging. The intracellular cAMP level in the ΔUvgap1 mutant was elevated, as UvGap1 plays an important role in maintaining the intracellular cAMP level by affecting the expression of phosphodiesterases, which are linked to cAMP degradation in U. virens. In a yeast two-hybrid assay, UvRas1 and UvRasGef (Ras guanyl nucleotide exchange factor) physically interacted with UvGap1. UvRas2 was identified as an interacting partner of UvGap1 through a bimolecular fluorescence complementation assay and affinity capture-mass spectrometry analysis. Taken together, these findings suggest that the UvGAP1-mediated Ras pathway is essential for the development and pathogenicity of U. virens.

Manual reduction in testicular torsion and subsequent treatment after successful reduction: a series of reports in a single institution.

Introduction: To explore the factors affecting the success of testicular torsion manual reduction and the safety of subsequent conservative treatment after successful reduction. Methods: Clinical data of 66 patients with testicular torsion treated in our emergency department from February 2017 to February 2022 were retrospectively collected. Manual reduction without anesthesia was performed in 19 patients. Patients with successful manual reduction chose different subsequent treatments according to the wishes of themselves and their guardians, including continuing conservative treatment and surgical exploration. Relevant clinical data were collected and analyzed. Results: Manual reduction was successful in 11 patients (11/19). Seven of them chose to continue conservative treatment, and four underwent surgical exploration immediately. Among the 7 patients who were treated conservatively, 3 underwent surgical treatment due to scrotal discomfort or testicular torsion at different stages, and the remaining 4 patients showed no recurrence of torsion during follow-up. Compared with other patients, patients with successful manual reduction had the shorter duration of pain (p < 0.05). The time from visiting our hospital to surgery in patients who attempted manual reduction was slightly shorter than those who underwent surgery directly (p > 0.05). The testes of these 11 patients were all successfully preserved. Conclusions: The short duration of pain may contribute to the success of manual reduction, and manual reduction did not increase the preparation time before surgery. Due to the unpredictable risk of recurrence, immediate surgical treatment is still recommended, or postponed elective surgical treatment should be offered in the next days or weeks.

In Situ Flash Synthesis of Ultra-High-Performance Metal Oxide Anode through Shunting Current-Based Electrothermal Shock.

The synthesis of anode materials plays an important role in determining the production efficiency, cost, and performance of lithium-ion batteries (LIBs). However, a low-cost, high-speed, scalable manufacturing process of the anode with the desired structural feature for practical technology adoption remains elusive. In this study, we propose a novel method called in situ flash shunt-electrothermal shock (SETS) which is controllable, fast, and energy-saving for synthesizing metal oxide-based materials. By using the example of direct electrothermal decomposition of ZIF-67 precursor loaded onto copper foil support, we achieve rapid (0.1-0.3 s) pyrolysis and generate porous hollow cubic structure material consisting of carbon-coated ultrasmall (10-15 nm) subcrystalline CoO/Co nanoparticles with controllable morphology. It was shown that CoO/Co@N-C exhibits prominent electrochemical performance with a high reversible capacity up to 1503.7 mA h g-1 after 150 cycles at 0.2 A g-1and stable capacities up to 434.1 mA h g-1 after 400 cycles at a high current density of 6 A g-1. This fabrication technique integrates the synthesis of active materials and the formation of electrode sheets into one process, thus simplifying the preparation of electrodes. Due to the simplicity and scalability of this process, it can be envisaged to apply it to the synthesis of metal oxide-based materials and to achieve large-scale production in a nanomanufacturing process.

Characterization, Semirational Design for pH Robustness, and the Application in Bioactive Peptide Production of a X-Prolyl Dipeptidyl Aminopeptidase from Lactococcus lactis MY-3.

PepXLcMY-3, an X-prolyl dipeptidyl aminopeptidase derived from Lactobacillus lactis MY-3, was screened and recombinantly expressed in Escherichia coli. The enzyme could exhibit about 40% activity within the pH range of 6.0-10. To further improve the pH robustness, site E396 located in the active pocket was discovered through alanine scanning. The mutant E396I displayed both developed activity and kcat/Km. The optimal pH of E396I shifted from 6.0 to 10 compared to WT, with the relative activity within the pH range of 6.0-10 significantly increased. The site K648 was then proposed by semirational design. The activity of mutant E396I/K648D reached 4.03 U/mg. The optimal pH was restored to 6.0, and the pH stability was further improved. E396I/K648D could totally hydrolyze ß-casomorphin 7 within 30 min. The hydrolysate showed 64.5% inhibition on angiotensin I converting enzyme, which was more efficient than those produced by E396I and WT, 23.2 and 44.7%, respectively.

Biotransformation of zearalenone to non-estrogenic compounds with two novel recombinant lactonases from Gliocladium.

BACKGROUND: The mycotoxin zearalenone (ZEA) produced by toxigenic fungi is widely present in cereals and its downstream products. The danger of ZEA linked to various human health issues has attracted increasing attention. Thus, powerful ZEA-degrading or detoxifying strategies are urgently needed. Biology-based detoxification methods are specific, efficient, and environmentally friendly and do not lead to negative effects during cereal decontamination. Among these, ZEA detoxification using degrading enzymes was documented to be a promising strategy in broad research. Here, two efficient ZEA-degrading lactonases from the genus Gliocladium, ZHDR52 and ZHDP83, were identified for the first time. This work studied the degradation capacity and properties of ZEA using purified recombinant ZHDR52 and ZHDP83. RESULTS: According to the ZEA degradation study, transformed Escherichia coli BL21(DE3) PLySs cells harboring the zhdr52 or zhdp83 gene could transform 20 µg/mL ZEA within 2 h and degrade > 90% of ZEA toxic derivatives, α/ß-zearalanol and α/ß-zearalenol, within 6 h. Biochemical analysis demonstrated that the optimal pH was 9.0 for ZHDR52 and ZHDP83, and the optimum temperature was 45 °C. The purified recombinant ZHDR52 and ZHDP83 retained > 90% activity over a wide range of pH values and temperatures (pH 7.0-10.0 and 35-50 °C). In addition, the specific activities of purified ZHDR52 and ZHDP83 against ZEA were 196.11 and 229.64 U/mg, respectively. The results of these two novel lactonases suggested that, compared with ZHD101, these two novel lactonases transformed ZEA into different products. The slight position variations in E126 and H242 in ZDHR52/ZEA and ZHDP83/ZEA obtained via structural modelling may explain the difference in degradation products. Moreover, the MCF-7 cell proliferation assay indicated that the products of ZEA degradation using ZHDR52 and ZHDP83 did not exhibit estrogenic activity. CONCLUSIONS: ZHDR52 and ZHDP83 are alkali ZEA-degrading enzymes that can efficiently and irreversibly degrade ZEA into non-estrogenic products, indicating that they are potential candidates for commercial application. This study identified two excellent lactonases for industrial ZEA detoxification.

UvVelC is important for conidiation and pathogenicity in the rice false smut pathogen Ustilaginoidea virens.

Rice false smut disease is one of the most significant rice diseases worldwide. Ustilaginoidea virens is the causative agent of this disease. Although several developmental and pathogenic genes have been identified and functionally analyzed, the pathogenic molecular mechanisms of U. virens remain elusive. The velvet family regulatory proteins are involved in fungal development, conidiation, and pathogenicity. In this study, we demonstrated the function of the VelC homolog UvVELC in U. virens. We identified the velvet family protein UvVELC and characterized its functions using a target gene deletion-strategy. Deletion of UvVELC resulted in conidiation failure and pathogenicity. The UvVELC expression levels during infection suggested that this gene might be involved in the early infection process. UvVELC is also important in resistance to abiotic stresses, the utilization efficiency of glucose, stachyose, raffinose, and other sugars, and the expression of transport-related genes. Moreover, UvVELC could physically interact with UvVEA in yeast, and UvVELC/UvVEA double-knockout mutants also failed in conidiation and pathogenicity. These results indicate that UvVELC play a critical role in the conidiation and pathogenicity in U. virens. Functional analysis indicated that UvVELC-mediated conidiation and nutrient acquisition from rice regulates the pathogenicity of U. virens. Understanding the function of the UvVELC homolog could provide a potential molecular target for controlling rice false smut disease.

Regulation of BTB (POZ) Structural Domain 6b by MicroRNA-222b in Zebrafish Embryos after Exposure to Di(2-ethylhexyl)phthalate at Low Concentrations.

Di-(2-ethylhexyl) phthalate (DEHP) is a sort of endocrine disruptor that induces abnormal physiological and biochemical activities such as epigenetic alterations, apoptosis, and oxidative stress. MicroRNAs (miRNAs) are a class of short noncoding RNAs that may regulate the expression of many protein-coding genes when organisms are exposed to environmental chemicals. miR-222b is a differentially expressed miRNA after DEHP exposure. miRNA-mRNA prediction suggested that BTB (POZ) structural domain 6b (BTBD6B) might be a target mRNA of miR-222b, and DEHP exposure altered its expression. However, the correlation between miR-222b and BTBD6B has not been experimentally confirmed. The aim of this study was to investigate the regulation of BTBD6B by miR-222b in zebrafish embryos under the effect of low concentration of DEHP. Dual fluorescent protein assays and dual luciferase reporter gene assays confirmed the interaction between miR-222b and the 3'-untranslated region (3'-UTR) of BTBD6B. Ectopic expression assays showed that miR-222b could negatively regulate BTBD6B in ZF4 cells. However, the relative expression of miR-222b and BTBD6B was significantly higher at both transcriptional and post-transcriptional levels in zebrafish embryos exposed to low concentrations of DEHP. The results of this study improved our understanding of the molecular mechanism of DEHP exposure toxicity. It identified that the aberrant expression of miR-222b/BTBD6B may be one of the mechanisms of DEHP toxicity, which can provide a theoretical reference and scientific basis for environmental management and biological health risk assessment.

NBD-based colorimetric and ratiometric fluorescent probe in NIR for bisulfite.

This work presented a FRET-ICT based fluorescent probe (named NTC) composed of coumarin-benzothiazole as the acceptor and 4-nitrobenzo[c][1,2,5] oxadiazole (NBD) as the donor for the detection of SO2 derivatives in NIR. Probe NTC possessed superior performance including selectivity, quickly response toward SO32-/HSO3- and high energy transfer efficiency (94 %). The test strips provided a simple and effective tool in detecting the presence of bisulfite. Besides, NTC was applied to test the sulfur dioxide derivatives in food samples and cells.

Effects of soda water on blood lipid and metabolic profiling of urine in hyperlipidemia rats using UPLC/Triple-TOF MS.

The effects of a natural soda water (Shi Han Quan, SHQ) on hyperlipidemia and the changes of urine metabolic profiling by metabolomics techniques were investigate. Thirty six Wistar rats weighing 160-200 g were divided into control group, hyperlipidemia (HL) group, and hyperlipidemia + SHQ water (SHQ) group. The metabolites in urine were determined using ultra high performance liquid chromatography-triple-time of flight-mass spectrometry (UPLC/Triple-TOF MS). At the end of 1 month and 3 months, the total glyceride (TG) level was significantly lower in SHQ group compared to HL group. There was no significantly difference in total cholesterol (TC) levels in HL group compared with SHQ group. The results showed that dinking SHQ water can improve the TG, but with no effects on TC. After drinking SHQ water for 3 months, the rats in different groups could be classified into different clusters according to the metabolites in urine. Total 15 important metabolites were found and correlated with disturbance of amino acid, phospholipid, fatty acid and vitamin metabolism, which suggested the changes of metabolism in the body and possible mechanism by which SHQ improved the TG. These findings provide a new insight for the prevention and control of hyperlipidemia.

Identification of an Alepterolic Acid Derivative as a Potent Anti-Breast-Cancer Agent via Inhibition of the Akt/p70S6K Signaling Pathway.

Alepterolic acid is a diterpene occurring in the fern Aleuritopteris argentea with potential biological activity that warrants further structural modification. In the present work, sixteen alepterolic acid derivatives were synthesized and evaluated for their anticancer activities. Among them, N-[m-(trifluoromethoxy)phenyl] alepterolamide displayed comparable activity (IC50 =4.20±0.21 µM) in MCF-7 cells. Moreover, mechanistic investigations indicated this compound was significantly capable of diminishing cell proliferation and viability of MCF-7 cells. After treatment with N-[m-(trifluoromethoxy)phenyl] alepterolamide, a significant increase in cleaved caspase-9, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP) and Bax/Bcl2 ratio were observed in MCF-7 cells, leading to caspase-dependent apoptotic pathways. Further studies showed this compound promoted cellular apoptosis and inhibited migration in MCF-7 cells via modulation of the Akt/p70S6K signaling pathway. All these results revealed the potential of N-[m-(trifluoromethoxy)phenyl] alepterolamide as an appealing therapeutic drug candidate for breast cancer.

Outbreak of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae ST15 in a Chinese teaching hospital: a molecular epidemiological study.

Background and Aims: The incidence of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) has been on the rise in China over the past five years, potentially leading to nosocomial epidemics. This study investigates the first outbreak of CRKP in the Second Affiliated Hospital of Jiaxing University. Methods: Between February 2021 and March 2022, 21 clinical isolates of OXA-232-producing CRKP were recovered from 16 patients in the Second Affiliated Hospital of Jiaxing University. We conducted antimicrobial susceptibility tests, whole genome sequencing, and bioinformatics to determine the drug resistance profile of these clinical isolates. Results: Whole-genome sequencing revealed that all 21 OXA-232-producing CRKP strains belonged to the sequence type 15 (ST15) and shared similar resistance, virulence genes, and plasmid types, suggesting clonal transmission between the environment and patients. Integrated genomic and epidemiological analysis traced the outbreak to two clonal transmission clusters, cluster 1 and cluster 2, including 14 and 2 patients. It was speculated that the CRKP transmission mainly occurred in the ICU, followed by brain surgery, neurosurgery, and rehabilitation department. Phylogenetic analysis indicated that the earliest outbreak might have started at least a year before the admission of the index patient, and these strains were closely related to those previously isolated from two major adjacent cities, Shanghai and Hangzhou. Comparative genomics showed that the IncFII-type and IncHI1B-type plasmids of cluster 2 had homologous recombination at the insertion sequence sites compared with the same type of plasmids in cluster 1, resulting in the insertion of 4 new drug resistance genes, including TEM-1, APH(6)-Id, APH(3'')-Ib and sul2. Conclusions: Our study observed the clonal spread of ST15 OXA-232-producing between patients and the hospital environment. The integration of genomic and epidemiological data offers valuable insights and facilitate the control of nosocomial transmission.

Resilience mediates the effect of peer victimization on quality of life in Chongqing adolescents: from a perspective of positive childhood experiences.

Background: Peer victimization is a harmful experience that contributed to one's psychological problems, physical health deterioration, and so on. Quality of life (QoL) is an important indicator of adolescent health assessment. To identify potential pathways of positive experiences in preventing peer victimization's detrimental effects and then provide intervention ideas for adolescent health, this study was conducted to examine the relationship between peer victimization and QoL in Chongqing adolescents and discover whether resilience plays a mediating role and positive childhood experiences (PCEs) act as a moderating role in the relationship. Methods: Data were the first follow-up of a cohort study conducted in four complete middle schools in two districts of Chongqing, China. Self-designed peer victimization items, the Connor-Davidson Resilience Scale, the Adolescent Quality of Life Scale, and the Benevolent Childhood Experiences Scale were used. We investigated the differences and correlations in peer victimization, QoL, and resilience between the two PCEs groups. Mplus version 8.3 was used to analyze the mediating role of resilience and the moderating role of PCEs in peer victimization and QoL. Results: Peer victimization, resilience, and QoL differed between the two PCEs groups (P < 0.001). Peer victimization negatively correlated with QoL and resilience, while resilience positively correlated with QoL (P < 0.001). In the models with total QOL as the dependent variable, the indirect effect was -0.431 (8.08% of the total effect) in the low-PCEs group vs. -2.077 (41.97% of the total effect) in the high-PCEs group. In the models with four dimensions of QOL as the dependent variable, the indirect effects ranged from -0.054 to -0.180 (6.07-12.95% of the total effects) in the low-PCEs group and from 0.295 to -0.823 in the high-PCEs group (35.89-68.76% of the total effects). Both total and indirect effects were significant (P < 0.05). In addition, the differences in indirect effects were significant between the two PCEs groups (P < 0.05), while differences in total and direct effects were almost not apparent. Conclusion: Resilience partially mediated the effect of peer victimization on QoL in Chongqing adolescents, and PCEs moderated this mediation. Schools, families, and society should focus on resilience intervention and prioritize the enhancement of PCEs for improving adolescent QoL.

Diagnostic and therapeutic effects of fluorescence cystoscopy and narrow-band imaging in bladder cancer: a systematic review and network meta-analysis.

BACKGROUND: This review aims to compare the efficacies of fluorescence cystoscopy, narrow-band imaging (NBI), and white light cystoscopy in the treatment and diagnosis of bladder cancer. METHODS: The authors searched PubMed, EMbase, Web of Science, and the Cochrane Library from January 1990 to April 2022. A total of 26 randomized controlled studies and 22 prospective single-arm studies were selected. Most patients had nonmuscle-invasive bladder cancer. The study protocol has been registered at PROSPERO. RESULTS: In the pairwise meta-analysis, 5-aminolevulinic acid (5-ALA) reduced the short-term and long-term recurrence rates of bladder cancer compared with white light cystoscopy (WLC); however, no statistical difference was observed in intermediate-term recurrence rates (RR=0.79, 95% CI: 0.57-1.09). Hexaminolevulinic acid and NBI reduced short-term, intermediate-term, and long-term recurrence rates. The sensitivity of 5-ALA, hexaminolevulinic acid, NBI, and WLC for bladder cancer were 0.89 (95% CI: 0.81-0.94), 0.96 (95% CI: 0.92-0.98), 0.96 (95% CI: 0.92-0.98), and 0.75 (95% CI: 0.70-0.79), respectively; however, only NBI had the same specificity as WLC (0.74 vs. 0.74). Compared with WLC, 5-ALA improved the detection rate of carcinoma in situ and Ta stage bladder cancer but had no advantage in T1 stage tumors (OR=2.39, 95% CI:0.79-7.19). Hexaminolevulinic acid and NBI improved the detection rates of all nonmuscular-invasive bladder cancers. In the network meta-analysis, there was no significant difference in either recurrence or detection rates between 5-ALA, hexaminolevulinic acid, and NBI. CONCLUSION: Fluorescence cystoscopy and NBI are advantageous for treating and diagnosing patients with nonmuscle-invasive bladder cancer.

Combined effects of particle size and humic acid corona on the aggregation kinetics of nanoplastics in aquatic environments.

Nanoplastics (NPs) contaminant in aquatic environments is one of the pressing environmental concerns globally. However, the combined effects of particle size and humic acid (HA) corona on the aggregation behavior of NPs have not been revealed yet. Therefore, this study explored the influence of HA corona on the aggregation kinetics of NPs with three different particle sizes under various water quality conditions. Results showed that in the absence of HA corona, the aggregation kinetic processes of all the three NPs were affected by the repulsive force originating from the hydration layer. Moreover, the smaller the particle size, the more obvious the effect. HA corona played a steric hindrance role for all the three NPs based on the extended-Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory in monovalent solutions, resulting in the impediment of aggregation. Whereas, in divalent solutions, the HA corona of 100 and 200 nm NPs experienced three stages: deformation, electrostatic-patch and bridging; while that of 40 nm NPs underwent electrostatic-patch and steric hindrance. The larger number of HA molecules distributed on 100 and 200 NPs surfaces led to more interactions with Ca2+ and NPs, which was the key factor for HA corona to play more diverse roles. According to the two dimension correlation spectroscopy analysis (2D-COS), the structural change in the interaction between HA and NPs was that the aromatic ring of NPs took precedence, followed by the carbonyl groups of HA. This study provided new insights into the combined effects of HA corona and particle size on the aggregation kinetics of NPs and established a theoretical foundation for predicting and assessing the transport and fate of NPs.

The Strength of hERG Inhibition by Erythromycin at Different Temperatures Might Be Due to Its Interacting Features with the Channels.

Erythromycin is one of the few compounds that remarkably increase ether-a-go-go-related gene (hERG) inhibition from room temperature (RT) to physiological temperature (PT). Understanding how erythromycin inhibits the hERG could help us to decide which compounds are needed for further studies. The whole-cell patch clamp technique was used to investigate the effects of erythromycin on hERG channels at different temperatures. While erythromycin caused a concentration-dependent inhibition of cardiac hERG channels, it also shifted the steady-state activation and steady-state inactivation of the channel to the left and significantly accelerated the onset of inactivation at both temperatures, although temperature itself caused a profound change in the dynamics of hERG channels. Our data also suggest that the binding pattern to S6 of the channels changes at PT. In contrast, cisapride, a well-known hERG blocker whose inhibition is not affected by temperature, does not change its critical binding sites after the temperature is raised to PT. Our data suggest that erythromycin is unique and that the shift in hERG inhibition may not apply to other compounds.

MAGE-B4, a binding partner of PRAMEF12, is dispensable for spermatogenesis and male fertility in mice.

Melanoma antigen (MAGE)-B4 belongs to the MAGE-B family genes, which are located on the X chromosome. The MAGE-B family genes are classified as cancer-testis antigens, as they are primarily expressed in the testis and are aberrantly expressed in most cancers. Although a no-stop mutation in MAGE-B4 causes rare X-linked azoospermia and oligozoospermia phenotype in humans, the specific function of MAGE-B4 on spermatogenesis in mice remains unclear. In this study, we identified MAGE-B4 as a binding partner of PRAME family member 12, which plays an important role in the maintenance of mouse spermatogenic lineage in juvenile testes. Additionally, we found that Mage-b4 transcripts were restricted to the testis and that Mage-b4 was specifically expressed in spermatogonia. To explore the function of MAGE-B4 in spermatogenesis, we generated a Mage-b4 knockout (KO) mouse model using CRISPR/Cas9 technology. However, we found that Mage-b4 KO males displayed normal testicular morphology and fertility. Further histological analysis revealed that all stages of spermatogenic cells were present in the seminiferous tubules of the Mage-b4 KO mice. Altogether, our data suggest that Mage-b4 is dispensable for mouse spermatogenesis and male fertility.

AIEgens for synergistic anticancer therapy.

Cancer is a mortal disease that can invade other parts of the body and cause severe complications. Despite their continuous progress, conventional cancer therapies including surgery, chemotherapy, and radiation therapy have their inherent limitations. To improve the precision of cancer treatment, maximize the therapeutic effect and minimize mortality, synergistic therapies combining imaging guiding technologies, phototherapy, and other therapies have emerged due to the mutually strengthening therapeutic efficacy. However, traditional organic phototherapeutic agents are limited since their aggregation in aqueous media usually affects both their luminescence behavior and therapeutic effect. In contrast, aggregate-induced emission luminogens (AIEgens) provide an ideal solution to develop phototherapy with bright fluorescence and a significant treatment effect in the aggregate state. Combining AIE-based phototherapy and conventional therapies benefits from synergistic effects and extends the potential of developing accurate cancer therapy. AIE-based synergistic therapy has been popularly discussed with such unexplored potential in recent years. This review will introduce the most recent progress of AIE-based synergistic cancer therapy.

Transcriptome profiling of the initial segment and proximal caput of mouse epididymis.

Background: The proximal region of the mouse epididymis plays a pivotal role in sperm transport, sperm maturation, and male fertility. Several studies have focused on segment-dependent gene expression of the mouse epididymis through high-throughput sequencing without the precision of the microdissection. Methods and results: Herein, we isolated the initial segment (IS) and proximal caput (P-caput) by physical microdissection using an Lcn9-cre; Rosa26tdTomato mouse model. We defined the transcriptome changes of caput epididymis by RNA sequencing (RNA-seq), which identified 1,961 genes that were abundantly expressed in the IS and 1,739 genes that were prominently expressed in the P-caput. In addition, we found that many differentially expressed genes (DEGs) were predominantly or uniquely expressed in the epididymis and region-specific genes were highly associated with transport, secretion, sperm motility, fertilization, and male fertility. Conclusion: Thus, this study provides an RNA-seq resource to identify region-specific genes in the caput epididymis. The epididymal-selective/specific genes are potential targets for male contraception and may provide new insights into understanding segment-specific epididymal microenvironment-mediated sperm transport, maturation, and male fertility.