A postmeiotically bifurcated roadmap of honeybee spermatogenesis marked by phylogenetically restricted genes.

Haploid males of hymenopteran species produce gametes through an abortive meiosis I followed by meiosis II that can either be symmetric or asymmetric in different species. Thus, one spermatocyte could give rise to two spermatids with either equal or unequal amounts of cytoplasm. It is currently unknown what molecular features accompany these postmeiotic sperm cells especially in species with asymmetric meiosis II such as bees. Here we present testis single-cell RNA sequencing datasets from the honeybee (Apis mellifera) drones of 3 and 14 days after emergence (3d and 14d). We show that, while 3d testes exhibit active, ongoing spermatogenesis, 14d testes only have late-stage spermatids. We identify a postmeiotic bifurcation in the transcriptional roadmap during spermatogenesis, with cells progressing toward the annotated spermatids (SPT) and small spermatids (sSPT), respectively. Despite an overall similarity in their transcriptomic profiles, sSPTs express the fewest genes and the least RNA content among all the sperm cell types. Intriguingly, sSPTs exhibit a relatively high expression level for Hymenoptera-restricted genes and a high mutation load, suggesting that the special meiosis II during spermatogenesis in the honeybee is accompanied by phylogenetically young gene activities.

Cascaded dual-channel broadband SPR fiber optic sensor based on Ag and Ag/ZnO/PDMS film structure.

In order to broaden the sensing bandwidth of surface plasmon resonance (SPR) sensors, we propose and demonstrate a dual-channel SPR fiber optic sensor with wide bandwidth. The sensor is fabricated using no-core fiber (NCF), in which the film consists of a silver film and a ZnO film. The sensing characteristics are investigated by simulation and experiment. The resonance wavelength range of the SPR sensor can be significantly tuned by varying the thickness of the ZnO film. In the experiments, a dual-channel SPR sensor that can be used for simultaneous detection of temperature and refractive index was realized by cascading ZnO/Ag film with Ag film. The experimental results show that the two sensing channels are independent without crosstalk. The sensitivity of this sensor is 3512 nm/RIU in the range of 1.333 ∼ 1.385 and 4.6 nm/°C in the range of 0 ∼ 60 °C, which is better than most of the current dual-channel SPR sensors. In addition, the experimental results show that this sensor has good stability in use. The sensor proposed in this work has the advantages of a wide operating wavelength range, simple and compact structure, and high sensitivity. It has a broad application prospect in the simultaneous measurement of refractive index and temperature of liquids.

Aspongopus chinensis ach-miR-276a-3p induces breast cancer cell cycle arrest by targeting APPL2 to regulate the CDK2-Rb-E2F1 signaling pathway.

Breast cancer, the most common cancer, presents a significant challenge to the health and longevity of women. Aspongopus chinensis Dallas is an insect with known anti-breast cancer properties. However, the anti-breast cancer effects and underlying mechanisms have not been elucidated. Exogenous microRNAs (miRNAs), which are derived from plants and animals, have been revealed to have notable capacities for controlling the proliferation of cancerous cells. To elucidate the inhibitory effects of miRNAs derived from A. chinensis and the regulatory mechanism involved in the growth of breast cancer cells, miRNA sequencing was initially employed to screen for miRNAs both in A. chinensis hemolymph and decoction and in mouse serum and tumor tissue after decoction gavage. Subsequently, the experiments were performed to assess the suppressive effect of ach-miR-276a-3p, the miRNA screened out from a previous study, on the proliferation of MDA-MB-231 and MDA-MB-468 breast cancer cell lines in vitro and in vivo. Finally, the regulatory mechanism of ach-miR-276a-3p in MDA-MB-231 and MDA-MB-468 breast cancer cells was elucidated. The results demonstrated that ach-miR-276a-3p notably inhibited breast cancer cell proliferation, migration, colony formation, and invasion and induced cell cycle arrest at the G0/G1 phase. Moreover, the ach-miR-276a-3p mimics significantly reduced the tumor volume and weight in xenograft tumor mice. Furthermore, ach-miR-276a-3p could induce cell cycle arrest by targeting APPL2 and regulating the CDK2-Rb-E2F1 signaling pathway. In summary, ach-miR-276a-3p, derived from A. chinensis, has anti-breast cancer activity by targeting APPL2 and regulating the CDK2-Rb-E2F1 signaling pathway and can serve as a promising candidate anticancer agent.

Visible-NIR surface plasmon resonance sensing technology for high precision refractive index detection.

Molybdenum disulfide (MoS2), as a representative transition metal disulfide material, has contributed significantly to the development of plasmonic technology toward the near-infrared (NIR). In this Letter, the physical mechanism of MoS2 excitation of surface plasmon resonance (SPR) in the NIR is investigated, and it is shown that the MoS2 film can induce the resonance dip to move toward the NIR and demonstrate a sensitivity higher than that in the visible band. A dual-channel SPR sensor capable of operating in the visible and NIR bands for refractive index (RI) detection was also prepared using the cascade method. The simulated and experimental results of the sensor show consistency. The experimental results show that the maximum sensitivity of the NIR detection channel is 14600 nm/RIU in the RI range of 1.333-1.420, which is 37% higher than the sensitivity of the visible channel. However, the visible channel has the advantage of a narrow FWHM. Therefore, the proposed cascaded dual-channel RI sensor combines high sensitivity and narrow FWHM. This dual-channel construction method improves the detection level of RI, promotes the development of SPR sensing technology to the NIR band and significantly improves the narrowband problem existing in the previous multi-channel sensing.

A clickable coenzyme A derived probe for investigating phosphopantetheinyl transferase activity in natural product biosynthesis.

Phosphopantetheinyl transferases activate carrier proteins through attachment of a coenzyme A derived phosphopantetheinyl linker. This study describes a method to monitor this process through a modified HSCoA with an alkyne group, allowing for the Cu-catalysed alkyne-azide cycloaddition of a fluorescent tag. Application of the method in an enzyme screening resulted in the identification of new promiscuous PPTases.

Enantioselective synthesis of all stereoisomers of geosmin and of biosynthetically related natural products.

Synthetic routes to geosmin and its enantiomer are well established, but the enantioselective synthesis of stereoisomers of geosmin is unknown. Here a stereoselective synthesis of all stereoisomers of geosmin is reported, yielding all compounds in high enantiomeric purity. Furthermore, the stereoselective synthesis of a geosmin derivative isolated from a mangrove associated streptomycete was performed, establishing the absolute configuration of the natural product. Finally, a new side product of the geosmin synthase from Streptomyces ambofaciens was isolated and its structure was elucidated by NMR spectroscopy. The absolute configuration of this new compound was determined through a stereoselective synthesis.

HSP gene superfamily in Aspongopus chinensis Dallas: unravelling identification, characterisation and expression patterns during diapause and non-diapause stages.

Aspongopus chinensis Dallas 1851, an insect of important economic value, faces challenges in artificial breeding due to mandatory diapause and limited access to wild resources. Heat shock proteins (Hsps) are thought to influence diapause in insects, but little is known about their role in A. chinensis during diapause. This study used genomic methods to identify 25 Hsp genes in A. chinensis, including two Hsp90, 14 Hsp70, four Hsp60 and five small Hsp genes, were located on seven chromosomes, respectively. The gene structures among the same families are relatively conserved. Meanwhile, the motif compositions and secondary structures of A. chinensis Hsps (AcHsps) were predicted. RNA-seq data and fluorescence quantitative PCR analysis showed that there were differences in the expression patterns of AcHsps in diapause and non-diapause stages, and AcHsp70-5 was significantly differentially expressed in both analysis, which was enriched in the pathway of response to hormone. All the results showed that Hsps play an important role in the diapause mechanism of A. chinensis. Our observations highlight the molecular evolution of the Hsp gene and their effect on diapause in A. chinensis.

Differential expression of microRNAs in diapause and non-diapause gonads of Aspongopus chinensis Dallas (Hemiptera: Dinidoridae): implications for reproductive control.

Aspongopus chinensis Dallas, 1851 (Hemiptera: Dinidoridae), an edible and medicinal insect, usually found in China and Southeast Asia, offers substantial potential for various applications. The reproductive cycle of this particular insect occurs annually because of reproductive diapause, leading to inadequate utilization of available natural resources. Despite its considerable ecological importance, the precise mechanisms underlying diapause in A. chinensis are not yet well understood. In this study, we conducted an analysis of comparing the microRNA (miRNA) regulation in the diapause and non-diapause gonads of A. chinensis and identified 303 differentially expressed miRNAs, among which, compared with the diapause group, 76 miRNAs were upregulated and 227 miRNAs downregulated. The results, regarding the Enrichment analysis of miRNA-targeted genes, showed their involvement in several essential biological processes, such as lipid anabolism, energy metabolism, and gonadal growth. Interestingly, we observed that the ATP-binding cassette pathway is the only enriched pathway, demonstrating the capability of these targeted miRNAs to regulate the reproductive diapause of A. chinensis through the above essential pathway. The current study provided the role of gonadal miRNA expression in the control of reproductive diapause in A. chinensis, the specific regulatory mechanism behind this event remained unknown and needed more investigation.

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis.

An isotopic labelling method was developed to investigate substrate binding by ketosynthases, exemplified by the second ketosynthase of the polyketide synthase BaeJ involved in bacillaene biosynthesis (BaeJ-KS2). For this purpose, both enantiomers of a 13C-labelled N-acetylcysteamine thioester (SNAC ester) surrogate of the proposed natural intermediate of BaeJ-KS2 were synthesised, including an enzymatic step with glutamate decarboxylase, and incubated with BaeJ-KS2. Substrate binding was demonstrated through 13C NMR analysis of the products against the background of various control experiments.

Engineering fungal terpene biosynthesis.

Covering: 2015 to 2022Fungal terpenoids are of large structural diversity and often exhibit interesting biological activities. Recent work has focused on two main aspects: (1) the discovery and understanding of unknown biosynthetic genes and pathways, and (2) the usage of already known biosynthetic genes in the construction of high yielding production strains. Both aspects will be covered in this review article that aims to summarise the most important work of the past few years.

Experimental study of an intensity-modulated curvature sensor with high sensitivity based on microstructured optical fiber.

Surface Plasmon Resonance (SPR) based fiber optic curvature sensors have the advantage of being insensitive to temperature and axial strain. However, they have the disadvantage of low sensitivity and small curvature detection range. To improve the performance of SPR curvature sensors, we propose an intensity-modulated microstructured optical fiber (MOF) curvature sensor. In this sensor, two no-core fibers (NCFs) are used as input-output couplers, and MOF with silver film deposited is used as sensing arms. The light in the cladding is used to excite the SPR, and the exciting resonant valley is extremely sensitive to slight bending changes. The performance of this sensor is investigated theoretically and experimentally. Numerical results show that its cladding pattern is more favorable in the excitation of SPR effects. Experimental results show that the cladding mode of MOF is very sensitive to curvature changes, thus giving it a great advantage in bending measurements. Its sensitivity reaches 0.18 dB/m-1, and linearity reaches 0.995 in the curvature range of 0-30 m-1. The sensor has the advantages of high sensitivity, low temperature and axial strain crosstalk, compact structure, and easy fabrication, which make it attractive in the field of bending sensing.

Mitochondrial outer membrane permeabilization and inner membrane permeabilization in regulating apoptosis and inflammation.

Recent studies delineate an intimate crosstalk between apoptosis and inflammation. However, the dynamic mechanism linking them by mitochondrial membrane permeabilization remains elusive. Here, we construct a mathematical model consisting of four functional modules. Bifurcation analysis reveals that bistability stems from Bcl-2 family member interaction and time series shows that the time difference between Cyt c and mtDNA release is around 30 min, which are consistent with previous works. The model predicts that Bax aggregation kinetic determines cells to undergo apoptosis or inflammation, and that modulating the inhibitory effect of caspase 3 on IFN-ß production allows the concurrent occurrence of apoptosis and inflammation. This work provides a theoretical framework for exploring the mechanism of mitochondrial membrane permeabilization in controlling cell fate.

Biphasic regulation of transcriptional surge generated by the gene feedback loop in a two-component system.

MOTIVATION: Transcriptional surges generated by two-component systems (TCSs) have been observed experimentally in various bacteria. Suppression of the transcriptional surge may reduce the activity, virulence and drug resistance of bacteria. In order to investigate the general mechanisms, we use a PhoP/PhoQ TCS as a model system to derive a comprehensive mathematical modeling that governs the surge. PhoP is a response regulator, which serves as a transcription factor under a phosphorylation-dependent modulation by PhoQ, a histidine kinase. RESULTS: Our model reveals two major signaling pathways to modulate the phosphorylated PhoP (P-PhoP) level, one of which promotes the generation of P-PhoP, while the other depresses the level of P-PhoP. The competition between the P-PhoP-promoting and the P-PhoP-depressing pathways determines the generation of the P-PhoP surge. Furthermore, besides PhoQ, PhoP is also a bifunctional modulator that contributes to the dynamic control of P-PhoP state, leading to a biphasic regulation of the surge by the gene feedback loop. In summary, the mechanisms derived from the PhoP/PhoQ system for the transcriptional surges provide a better understanding on such a sophisticated signal transduction system and aid to develop new antimicrobial strategies targeting TCSs. AVAILABILITY AND IMPLEMENTATION: https://github.com/jianweishuai/TCS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Feasibility and Long-Term Outcomes of the Crossboss/Stingray for Treating Coronary Chronic Total Occlusions Lesions with Distal Diffuse Disease Landing Zone.

BACKGROUND: The feasibility and long-term outcomes of the CrossBoss/Stingray for treating coronary chronic total occlusions (CTO) with distal diffuse disease landing zone remain unclear. METHODS: Consecutive CTO patients with distal diffuse lesions that underwent percutaneous coronary intervention by the CrossBoss/Stingray system at Xijing Hospital from April 2016 to October 2020, were included. Patients were analyzed by two groups according to the extent of stenosis in the distal landing zone: 50%-70% stenosis (moderate stenosis group) and >70% stenosis (severe stenosis group). The primary efficacy outcome was technical success, defined as the frequency of true lumen guidewire placement distal to the CTO. The composite endpoint of all-cause death, any stroke, or any revascularization was also explored. RESULTS: A total of 91 consecutive patients were included, with 32 patients in the moderate stenosis group and 59 patients in the severe stenosis group. The mean J-CTO score was 2.5 ± 1.1. The technical success rate was 79.1% (72/91) in the overall population and was similar between the 2 groups: 78.1% (25/32) and 79.7% (47/59) (p = 0.608). No coronary perforation occurred. With a median follow-up of 29 months (IQR: 53-92), the estimated rate of the composite endpoint of all-cause death, any stroke, or any revascularization was 50.4% (all-cause death: 16.6%, any stroke: 1.1%, any revascularization: 36.5%) in the overall population. No significant difference was observed in the rate of the composite endpoint between the moderate stenosis group and the severe stenosis group (45.1% vs. 54.3%, respectively, p = 0.797). CONCLUSIONS: In CTO lesions with distal diffuse disease landing zone, the technical success rates of CrossBoss/Stingray and the long-term clinical outcomes were not significantly different between the moderate stenosis group (50%-70%) and the severe stenosis group (>70%). However, the relatively high rate of long-term clinical outcomes, especially any revascularization, warrants further investigations on this indication in future studies.

The substrate scope of dehydratases in antibiotic biosynthesis and their application in kinetic resolutions.

Nine dehydratases involved in the biosynthesis of secondary metabolites in addition to FabZ from fatty acid biosynthesis were investigated for their substrate scope using a panel of N-acetylcysteamine (SNAC) thioesters. The best performing enzyme BorDH2 was applied in kinetic resolutions.

Network modeling-based identification of the switching targets between pyroptosis and secondary pyroptosis.

The newly identified cell death type, pyroptosis plays crucial roles in various diseases. Most recently, mounting evidence accumulates that pyroptotic signaling is highly correlated with coronavirus disease 2019 (COVID-19). Thus, understanding the induction of the pyroptotic signaling and dissecting the detail molecular control mechanisms are urgently needed. Based on recent experimental studies, a core regulatory model of the pyroptotic signaling is constructed to investigate the intricate crosstalk dynamics between the two cell death types, i.e., pyroptosis and secondary pyroptosis. The model well reproduces the experimental observations under different conditions. Sensitivity analysis determines that only the expression level of caspase-1 or GSDMD has the potential to individually change death modes. The decrease of caspase-1 or GSDMD level switches cell death from pyroptosis to secondary pyroptosis. Besides, eight biochemical reactions are identified that can efficiently switch death modes. While from the viewpoint of bifurcation analysis, the expression level of caspase-3 is further identified and twelve biochemical reactions are obtained. The coexistence of pyroptosis and secondary pyroptosis is predicted to be observed not only within the bistable range, but also within proper monostable range, presenting two potential different control mechanisms. Combined with the landscape theory, we further explore the stochastic dynamic and global stability of the pyroptotic system, accurately quantifying how each component mediates the individual occurrence probability of pyroptosis and secondary pyroptosis. Overall, this study sheds new light on the intricate crosstalk of the pyroptotic signaling and uncovers the regulatory mechanisms of various stable state transitions, providing potential clues to guide the development for prevention and treatment of pyroptosis-related diseases.

Conv-Former: A Novel Network Combining Convolution and Self-Attention for Image Quality Assessment.

To address the challenge of no-reference image quality assessment (NR-IQA) for authentically and synthetically distorted images, we propose a novel network called the Combining Convolution and Self-Attention for Image Quality Assessment network (Conv-Former). Our model uses a multi-stage transformer architecture similar to that of ResNet-50 to represent appropriate perceptual mechanisms in image quality assessment (IQA) to build an accurate IQA model. We employ adaptive learnable position embedding to handle images with arbitrary resolution. We propose a new transformer block (TB) by taking advantage of transformers to capture long-range dependencies, and of local information perception (LIP) to model local features for enhanced representation learning. The module increases the model's understanding of the image content. Dual path pooling (DPP) is used to keep more contextual image quality information in feature downsampling. Experimental results verify that Conv-Former not only outperforms the state-of-the-art methods on authentic image databases, but also achieves competing performances on synthetic image databases which demonstrate the strong fitting performance and generalization capability of our proposed model.

Cis double bond formation in polyketide biosynthesis.

Covering: up to 2020Polyketides form a large group of bioactive secondary metabolites that usually contain one or more double bonds. Although most of the double bonds found in polyketides are trans or E-configured, several cases are known in which cis or Z-configurations are observed. Double bond formation by polyketide synthases (PKSs) is widely recognised to be catalysed by ketoreduction and subsequent dehydration of the acyl carrier protein (ACP)-tethered 3-ketoacyl intermediate in the PKS biosynthetic assembly line with a specific stereochemical course in which the ketoreduction step determines the usual trans or more rare cis double bond configuration. Occasionally, other mechanisms for the installation of cis double bonds such as double bond formation during chain release or post-PKS modifications including, amongst others, isomerisations or double bond installations by oxidation are observed. This review discusses the peculiar mechanisms of cis double bond formation in polyketide biosynthesis.

Head Injury and Amyotrophic Lateral Sclerosis: A Meta-Analysis.

BACKGROUND: Prior studies have suggested that head injury might be a potential risk factor of amyotrophic lateral sclerosis (ALS). However, the association has not been well established. We aimed to provide a synopsis of the current understanding of head injury's role in ALS. METHODS: We performed a systematic search in PubMed for observational studies that quantitatively investigated the association between head injury and ALS risk published before April 10, 2020. We used a random-effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Fourteen eligible articles including 10,703 cases and 2,159,324 controls were selected in current meta-analysis. We found that head injury was associated with an increased risk of ALS (OR = 1.38, 95% CI: 1.20-1.60) and the association was slightly stronger concerning severe head injury and ALS risk (OR = 1.69, 95% CI: 1.27-2.23). Considering the number of head injuries (N) and ALS risk, the association was weak (OR = 1.23, 95% CI: 1.10-1.37, N = 1; OR = 1.29, 95% CI: 0.89-1.86, N ≥ 2). In addition, a strong association with ALS risk was found in individuals who suffered head injury <1 year (OR = 4.05, 95% CI: 2.79-5.89), and when the time lag was set at 1-5, 5-10, and >10 years, the pooled OR was 1.13, 1.35, and 1.10, respectively. CONCLUSION: This meta-analysis indicates that head injury, especially severe head injury, could increase ALS risk. Although a strong association is found between head injury <1 year and ALS risk in the current study, this result suggests a possibility of reverse causation.

Nine-month angiographic and 2-year clinical outcomes of the RECOVERY trial: A randomized study of the biodegradable polymer sirolimus-eluting COMBO dual-therapy stent versus a polymer-free sirolimus-eluting stent in Chinese patients.

OBJECTIVES: We evaluated the safety and efficacy of the novel dual-therapy sirolimus-eluting and endothelial progenitor cell (EPC) capture COMBO stent. BACKGROUND: (Very) late stent thrombosis (ST) and neo-atherosclerosis limit the performance of drug-eluting stents. The capture of EPCs accelerates stent re-endothelialization, thereby potentially decreasing the risk of restenosis and ST. METHODS: In total, 440 patients with de novo lesions in native coronary arteries were randomized (1:1) to either receive the COMBO stent (n = 220) or Nano polymer-free sirolimus-eluting stent (n = 220). The primary endpoint was the 9-month angiographic in-segment late lumen loss (LLL). Secondary endpoints included target lesion failure (TLF), a patient-oriented composite endpoint (PoCE), and ST. RESULTS: At 9 months, the COMBO in-segment LLL (0.29 ± 0.46 mm) was non-inferior to that of the Nano comparator stent (0.31 ± 0.44 mm; pnon-inferiority < .0001). Clinical outcomes were also similar between the COMBO and Nano stents, with TLF rates of 9.3% and 7.9% (p = .61) at 12 months, and 9.4% and 8.0% (p = .62) at 24 months, respectively. The PoCE rate was 14.8% and 10.6% (p = .19) at 12 months, and 16.0% and 11.3% (p = .16) at 24 months, respectively. Ischemia-driven target lesion revascularization rates were 6.0% and 3.7% (p = .26) at 12 months, and 6.2% and 3.8% (p = .26) at 24 months, respectively. No case of ST occurred in either group. CONCLUSIONS: The RECOVERY trial has shown the COMBO stent was effective, meeting the primary non-inferiority angiographic endpoint, and safe, with an overall low rate of clinical events in both stent groups, including no ST for up to 2 years.