A New Isolated Fungus and Its Pathogenicity for Apis mellifera Brood in China.

In this article, we report the pathogenicity of a new strain of fungus, Rhizopus oryzae to honeybee larvae, isolated from the chalkbrood-diseased mummies of honeybee larvae and pupae collected from apiaries in China. Based on morphological observation and internal transcribed spacer (ITS) region analyses, the isolated pathogenic fungus was identified as R. oryzae. Koch's postulates were performed to determine the cause-and-effect pathogenicity of this isolate fungus. The in vitro pathogenicity of this virulent fungus in honeybees was tested by artificially inoculating worker larvae in the lab. The pathogenicity of this new fungus for honeybee larvae was both conidial-concentration and exposure-time dependent; its highly infectious and virulent effect against the larvae was observed at 1 × 105 conidia/larva in vitro after 96 h of challenge. Using probit regression analysis, the LT50 value against the larvae was 26.8 h at a conidial concentration of 1 × 105 conidia/larva, and the LC50 was 6.2 × 103 conidia/larva. These results indicate that the new isolate of R. oryzae has considerable pathogenicity in honeybee larvae. Additionally, this report suggests that pathogenic phytofungi may harm their associated pollinators. We recommend further research to quantify the levels, mechanisms, and pathways of the pathogenicity of this novel isolated pathogen for honeybee larvae at the colony level.

SADR: Self-Supervised Graph Learning With Adaptive Denoising for Drug Repositioning.

Traditional drug development is often high-risk and time-consuming. A promising alternative is to reuse or relocate approved drugs. Recently, some methods based on graph representation learning have started to be used for drug repositioning. These models learn the low dimensional embeddings of drug and disease nodes from the drug-disease interaction network to predict the potential association between drugs and diseases. However, these methods have strict requirements for the dataset, and if the dataset is sparse, the performance of these methods will be severely affected. At the same time, these methods have poor robustness to noise in the dataset. In response to the above challenges, we propose a drug repositioning model based on self-supervised graph learning with adptive denoising, called SADR. SADR uses data augmentation and contrastive learning strategies to learn feature representations of nodes, which can effectively solve the problems caused by sparse datasets. SADR includes an adaptive denoising training (ADT) component that can effectively identify noisy data during the training process and remove the impact of noise on the model. We have conducted comprehensive experiments on three datasets and have achieved better prediction accuracy compared to multiple baseline models. At the same time, we propose the top 10 new predictive approved drugs for treating two diseases. This demonstrates the ability of our model to identify potential drug candidates for disease indications.

Distribution and sources of polycyclic aromatic hydrocarbons in surface sediments of the East China marginal seas: Significance of the terrestrial input and shelf mud deposition.

To investigate the distribution, sources, influencing factors, and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in East China Marginal Seas (ECMSs) sediments, we measured the concentrations of 16 PAHs in 104 surface sediment samples collected from the ECMSs in 2014 and 2016. Total PAH concentration (∑PAHs) ranged from 4.49 to 163.66 ng/g dry weight (dry w), with 65.98 ± 33.00 (mean ± SD) ng/g dry w. The highest PAH concentrations and total organic carbon were observed in areas with fine-grained sediments in the Bohai Sea (BS), Yellow Sea (YS), and coastal East China Sea (ECS), indicating the prominent influence of regional hydrodynamics and sediment properties. The dominant PAH congener in BS and YS was BbF, whereas coastal ECS was Phe. The heterogeneity of PAH sources implies that terrestrial PAH input and shelf mud deposition have crucial roles in the source-sink processes of PAHs in a strongly human-influenced marginal sea.

A comprehensive exploration of characteristics and source attribution of carbonaceous aerosols in PM2.5 in an East China megacity.

A total of 84 PM2.5 (fine particulate matter) aerosol samples were collected between October 2020 and August 2021 within an urban site in Hangzhou, an East China megacity. Chemical species, such as organic carbon (OC), elemental carbon (EC), as well as char, soot, and n-alkanes, were analyzed to determine their pollution characteristics and source contributions. The mean yearly concentrations of OC, EC, char, soot, and total n-alkanes (∑n-alkane) were 8.76 ± 3.61 µg/m3, 1.44 ± 0.76 µg/m3, 1.21 ± 0.69 µg/m3, 0.3 ± 0.1 µg/m3, and 24.2 ± 10.6 ng/m3. The OC, EC, and ∑n-alkanes were found in the highest levels during winter and lowest during summer. There were strong correlations between OC and EC in both winter and spring, suggesting similar potential sources for these carbonaceous components in both seasons. There were poor correlations among the target pollutants due to summertime secondary organic carbon formation. Potential source contribution functions analysis showed that local pollution levels in winter and autumn were likely influenced by long-range transportation from the Plain of North China. Source index and positive matrix factorization models provided insights into the complex sources of n-alkanes in Hangzhou. Their major contributors were identified as terrestrial plant releases (32.7%), traffic emissions (28.8%), coal combustion (27.3%), and microbial activity (11.2%). Thus, controlling vehicular emissions and coal burning could be key measures to alleviate n-alkane concentrations in the atmosphere of Hangzhou, as well as other Chinese urban centers.

Inverse design of an ultra-compact and large-bandwidth bent subwavelength grating wavelength demultiplexer.

Inverse design has attracted significant attention as a method to improve device performance and compactness. In this research, we employed a combination of forward design and the inverse algorithm using particle swarm optimization (PSO) to design a bent ultra-compact 1310/1550 nm broadband wavelength demultiplexer assisted by a subwavelength grating (SWG). Through the phase matching at 1550 nm and the phase mismatch at 1310 nm, we rapidly designed the width parameters of SWG in the forward direction. Then the PSO algorithm was used to optimize the SWG parameters in a certain range to achieve the best performance. Additionally, we introduced a new bent dimension significantly reducing the device length while maintaining low insertion loss (IL) and high extinction ratios (ERs). It has been verified that the length of the device is only 7.8 µm, and it provides a high ER of 24 dB at 1310 nm and 27 dB at 1550 nm. The transmitted spectrum shows that the IL values at both wavelengths are below 0.1 dB. Meanwhile, the 1 dB bandwidth exceeds 150 nm, effectively covering the entire O-band and C-band. This approach has been proven successful in enhancing performance and significantly reducing the device footprint.

Designing M13 Bacteriophage and Fe-Nanonest Self-Assembly System for Universal and Facile Preparation of Metal Single Atoms as Stable Mimicking Enzymes.

Metal single-atom catalysts (MSACs) possess multiple advantages in chemical synthesis; their efficient fabrication routes, however, remain a challenge to date. Here, an interdisciplinary design using M13 bacteriophage virus as a biotemplate to carry Fe nanoclusters, which we figuratively call "Fe-nanonests", is proposed to enable facile and versatile synthesis of MSACs. The feasibility and generality of this self-assembly method was demonstrated by the observation of six different metal single atoms (MSAs) including Ag, Pt, Pd, Zn, Cu, and Ni. With Pd as a representative, key factors dominating the fabrication were determined. The Pd single atoms exhibited excellent horseradish peroxidase (HRP)-like activity, which was further improved by 50% via genetic editing of the M13 pVIII protein terminals. Excellent stability was also observed in the quantification of acid phosphatase, a cancer predictor. X-ray absorption near-edge structure spectroscopy has been applied to the analysis of Pd single atoms as well, and the Pd-N4 coordination explained the mechanism of high HRP-like catalytic activity. The MSAs synthesized by the M13 phage and Fe-nanonest self-assembly method show promising prospects in non-cold-chain medical detection applications.

Comparative proteomic analysis identifies proteins associated with arbuscular mycorrhizal symbiosis in Poncirus trifoliata.

Citrus, one of the most widely cultivated fruit crops in the world, relies on arbuscular mycorrhizal fungi (AMF) to absorb nutrients and water from soil. However, the molecular mechanism of AM symbiosis (AMS) in citrus in general have largely been understudied. Here, using a TMT labeling proteomic approach, we identified 365 differentially expressed proteins (DEPs) in roots of Poncirus trifoliata (a common citrus rootstock) upon Rhizophagus irregularis colonization as compared with uninoculated roots, of which 287 were up-regulated and 78 were down-regulated. GO analysis revealed that the DEPs were mainly involved in biological processes such as negative regulation of endopeptidase inhibitor activity, negative regulation of endopeptidase, one-carbon metabolic process and carbohydrate metabolic process. KEGG enrichment analysis indicated that the DEPs were mainly involved in regulating metabolic pathways such as fatty acid biosynthesis, phenylpropanoid biosynthesis and carbon metabolism. Furthermore, 194 of the 365 DEPs were found to be associated with AMS-responsive genes by association analysis with our previous transcriptomes data, which highlighted the important roles of these proteins in AMS. One of the 194 DEPs, neutral ceramidase (PtNCER), was further chosen for function analysis via RNAi interfering its homologous gene MtNCER in a mycorrhizal model plant Medicago truncatula, which confirmed a positive role of NCER in AM establishment. Our results provided basic data and key candidate genes for genetic improvement of efficient nutrient uptake through AM establishment in citrus and other crops.

Insights into myopic choroidal neovascularization based on quantitative proteomics analysis of the aqueous humor.

BACKGROUND: Previous studies on the biomarkers of pathologic myopia choroidal neovascularization (pmCNV) development merely detected limited types of proteins and provide a meagre illustration of the underlying pathways. Hence, a landscape of protein changes in the aqueous humor (AH) of pmCNV patients is lacking. Here, to explore the potential mechanisms and biomarkers of pmCNV, we analyzed the clinical data and protein profile among atrophic (A) lesions, tractional lesions (T) and neovascular (N) lesions in myopic patients based on the ATN grading system for myopic maculopathy (MM). RESULTS: After investigating demographic data of our patients, a correlation was found between A and N lesions (R = 0.5753, P < 0.0001). Accordingly, groups were divided into patients without MM, patients with myopic atrophic maculopathy (MAM), and patients with pmCNV (N2a lesion). In proteomics analysis, the increased protein level of GFAP and complement-associated molecules in AH samples of the 3 groups also indicated that MAM and pmCNV shared similar characteristics. The GO enrichment and KEGG pathway analysis were performed, which mapped that differential expressed proteins mainly engaged in JAK-STAT pathway between the pmCNV group and two controls. Furthermore, we identified several potential biomarkers for pmCNV, including FCN3, GFAP, EGFR, SFRP3, PPP2R1A, SLIT2, and CD248. CONCLUSIONS: Atrophic lesions under pathologic myopic conditions demonstrated similarities to neovascularization development. Potential biomarkers including GFAP were associated with the pathogenesis of pmCNV. In summary, our study provides new insights for further research on pmCNV development.

Corrigendum: Therapy by physician-pharmacist combination and economic returns for cancer pain management in China: a cost-effectiveness analysis.

[This corrects the article DOI: 10.3389/fphar.2023.1073939.].

Semantic-enhanced Graph Contrastive Learning with Adaptive Denoising for Drug Repositioning.

The traditional drug development process requires a significant investment in workforce and financial resources. Drug repositioning as an efficient alternative has attracted much attention during the last few years. Despite the wide application and success of the method, there are still many shortcomings in the existing model. For example, sparse datasets will seriously affect the existing methods' performance. Additionally, these methods do not pay attention to the noise in datasets. In response to the above defects, we propose a semantic-enriched augmented graph contrastive learning with an adaptive denoising method, called SGCD. This method enhances data from the perspective of the embedding layer, deeply mines potential neighborhood relation-ships in semantic space, and combines similar drugs in the semantic neighborhoods into prototype comparison targets, thus effectively mitigating the impact of data sparsity on the model. Moreover, to enhance the model's robustness to noisy data, we use the adaptive denoising method, which can effectively identify noisy data in the training process. Exhaustive experiments on multiple real datasets show the effectiveness of the proposed model. The code implementation is available at https://github.com/yuhuimin11/SGCD-master.

Self-Assembly of Cluster-Mediated 3D Catenanes with Size-Specific Recognition Behavior.

Although interlocked three-dimensional molecules display unique properties associated with their spatial structures, their synthesis and study of their host-guest properties remain challenging. We report the formation of a novel [2]catenane, [Et4N]@[(Tp*WS3Cu3Cl)2(cis-bpype)3]2(OTf)5 ([Et4N][1](OTf)5), by self-assembly of the cluster node [Tp*WS3Cu3Cl]+ and the organic linker (Z)-1,2-diphenyl-1,2-bis(4-(pyridin-4-yl)phenyl)ethene (cis-bpype). Single-crystal X-ray and NMR analyses established that [1]4+ is formed by the interpenetration of two cluster-organic cages. Unique cation-in-cation host-guest complexes were observed with this catenane. The crystalline, empty catenane was formed by taking advantage of the electrostatic repulsion-induced weak binding of the host. Encapsulation experiments also reveal that the empty catenane can adaptively encapsulate cations such as [Et4N]+ and [Pr4N]+ in the cross cavity but is unable to encapsulate [Bu4N]+ and [Me4N]+, although the size of the latter is compatible with that of the cavity. Theoretical calculations and volume analysis allow to unravel the ingenious role of catenane structures and the interplay between electrostatic repulsion and attractive noncovalent interactions for size-specific recognition behavior in host-guest systems involving species with similar electric charges.

Emerging materials and technologies for electrocatalytic seawater splitting.

The limited availability of freshwater in renewable energy-rich areas has led to the exploration of seawater electrolysis for green hydrogen production. However, the complex composition of seawater presents substantial challenges such as electrode corrosion and electrolyzer failure, calling into question the technological and economic feasibility of direct seawater splitting. Despite many efforts, a comprehensive overview and analysis of seawater electrolysis, including electrochemical fundamentals, materials, and technologies of recent breakthroughs, is still lacking. In this review, we systematically examine recent advances in electrocatalytic seawater splitting and critically evaluate the obstacles to optimizing water supply, materials, and devices for stable hydrogen production from seawater. We demonstrate that robust materials and innovative technologies, especially selective catalysts and high-performance devices, are critical for efficient seawater electrolysis. We then outline and discuss future directions that could advance the techno-economic feasibility of this emerging field, providing a roadmap toward the design and commercialization of materials that can enable efficient, cost-effective, and sustainable seawater electrolysis.

Sources of polychlorinated biphenyls (PCBs) in sediments of the East China marginal seas: Role of unintentionally-produced PCBs.

The production and use of intentionally-produced polychlorinated biphenyls (PCBs) in China have a short history compared with countries of North America and Europe, where technical PCB mixtures were manufactured in large amounts for decades before being banned. Unintentionally-produced PCB emissions increased dramatically in China, leading to unique profiles of PCB burdens. This study first time evaluated 208 individual PCB congeners at 94 sites from surface sediments of the East China Marginal Seas (ECMSs) and explored their sources. Non-technical PCBs transported from atmospheric transport and river discharge played a dominant role in most areas of the ECMSs, while historical residuals of technical PCBs occupied the fine-grained sediments in muddy areas of the central Yellow Sea (YS), regarding to the low sedimentation rate in the central YS. Furthermore, emissions from Taizhou located on the coast of the East China Sea (ECS), which is an important electronic waste dismantling site in East China, contributed additional technical PCBs to the inner shelf of the ECS. Our results indicate that non-technical PCBs have become the dominant PCB species in the ECMSs, and emphasize the synergistic effects of large riverine input, long-range atmospheric transport, and muddy shelf deposition on PCB source and sink of in marginal seas.

Iodine-125 Brachytherapy for Palliative Treatment of Painful Colorectal Cancer Port-Site Metastases.

OBJECTIVE: To summarize the treatment process of a case of Iodine-125 Brachytherapy for Palliative Treatment of Painful Colorectal Cancer Port-Site Metastases. METHODS: We present a case report of multifocal port-site metastases ( PSMs ) that developed in a patient with stage IV ascending colonic adenocarcinoma and mucinous cancer following laparoscopic surgery. After multiline therapy failed, painful PSMs treated with repeated iodine-125 seed implantation. RESULTS: Severe abdominal discomfort were eventually successfully managed after receiving iodine-125 brachytherapy. CONCLUSION: For painful PSMs, iodine-125 brachytherapy can be a safe and effective treatment option.

All-optical spiking neural network and optical spike-time-dependent plasticity based on the self-pulsing effect within a micro-ring resonator.

In this paper, we proposed an all-optical version of photonic spiking neurons and spike-time-dependent plasticity (STDP) based on the nonlinear optical effects within a micro-ring resonator. In this system, the self-pulsing effect was exploited to implement threshold control, and the equivalent pulse energy required for spiking, calculated by multiplying the input pulse power amplitude with its duration, was about 14.1 pJ. The positive performance of the neurons in the excitability and cascadability tests validated the feasibility of this scheme. Furthermore, two simulations were performed to demonstrate that such an all-optical spiking neural network incorporated with STDP could run stably on a stochastic topology. The essence of such an all-optical spiking neural network is a nonlinear spiking dynamical system that combines the advantages of photonics and spiking neural networks (SNNs), promising access to the high speed and lower consumption inherent to optical systems.

Therapy by physician-pharmacist combination and economic returns for cancer pain management in China: a cost-effectiveness analysis.

Objective: To examine whether joint management of cancer pain by physicians and pharmacists in clinics provides economic advantages from the perspective of the Chinese healthcare system. Methods: From February 2018 to March 2020, 100 patients who visited the joint cancer pain clinic at the Xiangya Hospital of Central South University were included. These patients were randomly assigned to either the control or intervention groups. The control group received regular outpatient services from a physician, while the intervention group received regular outpatient services from a physician and medication education provided by a pharmacist. The study considered various direct costs, including drug expenses, physician-pharmacist outpatient services, adverse event management, consultations, examinations, and readmissions. The outcome indicators considered were the cancer pain control rate and the reduction in pain scores. Decision tree modeling, single-factor sensitivity analysis, and probabilistic sensitivity analysis were performed to evaluate the cost-effectiveness of joint physician-pharmacist outpatient services compared to physician-alone outpatient services. Results: The intervention group showed a significantly higher cancer pain control rate than the control group (0.69 vs. 0.39, p = 0.03). In the decision tree model, the intervention group had a significantly lower pain score than the control group (0.23 vs. 0.14). The cost per person in the intervention group was $165.39, while it was $191.1 per person in the control group. The univariate sensitivity analysis showed that the cost of self-management for patients in the control group was identified as the primary sensitivity factor. Probabilistic sensitivity analysis indicated that the joint clinic group had a favorable incremental cost-effectiveness compared to the physician clinic group. In addition, the probabilistic sensitivity analysis demonstrated an absolute advantage in the incremental cost-effectiveness of the joint clinic group over the outpatient physician group. Conclusion: The participation of pharmacists in joint cancer pain clinic services led to improved pain management for patients, demonstrating a clear advantage in terms of cost-effectiveness.

Combination therapy with budesonide and acetylcysteine alleviates LPS-induced acute lung injury via the miR-381/NLRP3 molecular axis.

BACKGROUND: Acute lung injury (ALI) usually has a high morbidity and mortality rate, but the current treatment is relatively scarce. Both budesonide (Bud) and N-acetylcysteine (NAC) exhibit protective effects in ALI, so we further investigated whether they have a synergistic effect on ALI when used together. METHODS: Establishment of a rat model of ALI with Lipopolysaccharide (LPS). Bud and NAC were administered by nebulized inhalation alone or in combination. Subsequently, HE staining was performed to observe the pathological changes in lungs of rat. Evans blue staining was implemented to assess alveolar permeability, and the pulmonary edema was assessed by measuring the ratio of wet to dry weight of the lung. Moreover, a TUNEL kit was served to test apoptosis in lung tissues. Western blot and immunohistochemistry were analyzed for expression of scorch-related proteins and NLRP3 in lung tissue, respectively. ELISA was implemented to detect inflammatory factor levels in BALF. and RT-qPCR was utilized to assess the expression level of miR-381. After stable transfection of miR-381 inhibitor or OE-NLRP3 in BEAS-2B treated with LPS, Bud and NAC, miR-381 expression was assessed by RT-qPCR, scorch death-related protein expression was measured by western blot, cell proliferation/viability was assayed by CCK-8, apoptosis was measured by flow cytometry, and ELISA was implemented to assess inflammatory factor levels. Furthermore, the Dual-luciferase assay was used to verify the targeting relationship. RESULTS: Bud and NAC treatment alone or in combination with nebulized inhalation attenuated the increased alveolar permeability, pulmonary edema, inflammatory response and scorching in LPS-induced ALI rats, and combined treatment with Bud and NAC was the most effective. In addition, combined treatment with Bud and NAC upregulated miR-381 expression and inhibited NLRP3 expression in cellular models and LPS-induced ALI rats. Transfection of the miR-381 inhibitor and OE-NLRP3 partially reversed the protective effects of Bud and NAC combination treatment on BEAS-2B cell proliferation inhibition, apoptosis, focal death and the inflammatory response. CONCLUSION: Combined Bud and NAC nebulization therapy alleviates LPS-induced ALI by modulating the miR-381/NLRP3 molecular axis.

Antibody Kinetics after Three Doses of SARS-CoV-2 mRNA Vaccination in Patients with Inflammatory Bowel Disease.

Background: The emergence of new SARS-CoV-2 variants calls for more data on SARS-CoV-2 mRNA vaccine response. Aims: We aimed to assess the response to a third mRNA vaccine dose against SARS-CoV-2 in inflammatory bowel disease (IBD) patients. Methods: This was a single-center, observational prospective study of IBD patients who received a third mRNA vaccine dose against SARS-CoV-2. Antibody titers were taken post-third-dose at one and three months using the Roche Elecsys anti-SARS-CoV-2-S enzyme immunoassay. Titers less than 0.8 units/mL were considered negative according to the manufactures. Titers between 0.8 units/mL and 250 units/mL were considered non-neutralizing. Titers greater than 250 units/mL were considered neutralizing. Results: Eighty-three patients were included, all of whom had detectable antibodies at 3 months post-third dose. A total of 89% showed neutralizing and 11% non-neutralizing titers. Participants with non-neutralizing titers were more likely to be on systemic corticosteroids (p = 0.04). Two participants seroconverted from negative to positive, whereas 86% with non-neutralizing titers boosted to neutralizing levels. Only one participant with neutralizing titers after a third dose had a decrease to a non-neutralizing level within 3 months. Conclusions: Our findings support the ongoing recommendations for additional doses in immunocompromised individuals. However, longitudinal studies with a greater-sized patient population are needed.

GmUFO1 Regulates Floral Organ Number and Shape in Soybean.

The UNUSUAL FLORAL ORGANS (UFO) gene is an essential regulatory factor of class B genes and plays a vital role in the process of inflorescence primordial and flower primordial development. The role of UFO genes in soybean was investigated to better understand the development of floral organs through gene cloning, expression analysis, and gene knockout. There are two copies of UFO genes in soybean and in situ hybridization, which have demonstrated similar expression patterns of the GmUFO1 and GmUFO2 genes in the flower primordium. The phenotypic observation of GmUFO1 knockout mutant lines (Gmufo1) showed an obvious alteration in the floral organ number and shape and mosaic organ formation. By contrast, GmUFO2 knockout mutant lines (Gmufo2) showed no obvious difference in the floral organs. However, the GmUFO1 and GmUFO2 double knockout lines (Gmufo1ufo2) showed more mosaic organs than the Gmufo1 lines, in addition to the alteration in the organ number and shape. Gene expression analysis also showed differences in the expression of major ABC function genes in the knockout lines. Based on the phenotypic and expression analysis, our results suggest the major role of GmUFO1 in the regulation of flower organ formation in soybeans and that GmUFO2 does not have any direct effect but might have an interaction role with GmUFO1 in the regulation of flower development. In conclusion, the present study identified UFO genes in soybean and improved our understanding of floral development, which could be useful for flower designs in hybrid soybean breeding.

AAV induces hepatic necroptosis and carcinoma in diabetic and obese mice dependent on Pebp1 pathway.

Obesity and diabetes are risk factors for hepatocellular carcinoma (HCC); however, the underlying mechanisms are yet to be elucidated. Adeno-associated virus (AAV) frequently infects humans and has been widely used in gene therapy, but the risk of AAV infection such as HCC should be further evaluated. Here, we show that recombinant AAV injection caused liver injury, hepatic necroptosis, and HCC in db/db or high-fat diet-induced hyperglycemic and obese mice, but not in mice with only hyperglycemia or obesity. Prednisone administration or knockdown of Pebp1, highly expressed in db/db mice, alleviated hepatic injury and necroptosis induced by recombinant AAV in mice with diabetes and obesity. Inhibition of Pebp1 pathway also attenuated inflammation and necroptosis in vitro. Our findings show that AAV infection is a critical risk factor for HCC in patients with diabetes and obesity, and AAV gene therapy for these patients should be carefully evaluated. Both prednisone treatment and targeting Pebp1 pathway are promising strategies to alleviate inflammation and necroptosis that occurred in AAV gene therapy or related diseases.