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Abstract Background EYA4 variants are responsible for DFNA10 deafness. Due to its insidious onset and slow progression, hearing loss in autosomal dominant non-syndromic hearing loss (ADNSHL) is usually challenging to detect early in clinical settings, with limited intervention options. Genetic testing can aid in early detection of hearing loss, enabling timely intervention to reduce disability rates and improve the quality of life. Methods In this study, we report the case of a Chinese family with postlingual and progressive hearing loss that was passed down for four generations. Whole-exome sequencing (WES) was performed on DNA samples from the proband. Candidate variants identified in the proband and family members were confirmed via Sanger sequencing. In silico prediction tools and co-segregation analyses were used to assess the pathogenicity of identified variants. A literature review of known EYA4 variants was performed, analysing variant frequency, distribution characteristics across different populations, and genotype-phenotype correlations. Results We identified a novel EYA4 variant, c.1745_1748del (p.Glu582ValfsTer6), in a Chinese family with ADNSHL, and co-segregation with the family’s phenotype was confirmed. The audiometry showed mid-to-high frequency downsloping hearing loss. To date, 52 pathogenic variants of EYA4 have been reported, with majority identified in Asian populations. Most observed are the missense and frameshift variants. Conclusions A novel variant of EYA4 was identified in a Chinese family with postlingual hearing loss, contributing to the expanding spectrum of EYA4 variants. The audiological features of EYA4 variants are highly heterogeneous and often challenging to detect early in clinical settings. Our findings highlight the significance of genetic testing in patients presenting with postlingual hearing loss.

Based on autumn precipitation data from 1961 to 2021 in Shanxi Province， NCEP/NCAR reanalysis data， and sea surface temperature data， the spatial-temporal variation characteristics and cause diagnosis of autumn precipitation in Shanxi Province were analyzed and discussed by using EOF analysis， correlation analysis and regression analysis.The results show that the autumn precipitation in Shanxi Province was relatively high before the mid-1970s， but decreased afterwards， and began to increase again in the mid-2000s.Further exploration of the causes of this interdecadal variation from the perspective of atmospheric circulation reveals that， during periods of excessive precipitation， the 200 hPa latitudinal wind field is located in the north of the East Asian westerly jet， which is beneficial for enhancing the upward movement in Shanxi； The 500 hPa geopotential height field exhibits a significant “+-+” anomaly distribution in the Europe and Asia region， which is conducive to the southward eruption of high latitude cold air； The 850 hPa wind field is conducive to the transport of low latitude water vapor to Shanxi， and under such high and low altitude circulation configuration， it is conducive to an increase in precipitation in Shanxi.At the same time， there is a close relationship between autumn precipitation and sea surface temperature anomaly in Shanxi.When the sea surface temperature in the central North Pacific is higher and in the tropical Middle East Pacific is lower from March to May， the autumn precipitation in the southern part of Shanxi is prone to behigher.

Alzheimer’s Disease (AD) is a multifaceted neurodegenerative disease predominantly defined by the extracellular accumulation of amyloid-β (Aβ) peptide. In light of this, in the past decade, several clinical approaches have been used aiming at developing peptides for therapeutic use in AD. The use of cationic arginine-rich peptides (CARPs) in targeting protein aggregations has been on the rise. Also, the process of peptide development employing computational approaches has attracted a lot of attention recently. Using a structure database containing pentapeptides made from 20 L-α amino acids, we employed molecular docking to sort pentapeptides that can bind to Aβ42, then performed molecular dynamics (MD) analyses, including analysis of the binding stability, interaction energy, and binding free energy to screen ligands. Transmission electron microscopy (TEM), circular dichroism (CD), thioflavin T (ThT) fluorescence detection of Aβ42 polymerization, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and the flow cytometry of reactive oxygen species (ROS) were carried out to evaluate the influence of pentapeptides on the aggregation and cell toxicity of Aβ42. Two pentapeptides (TRRRR and ARRGR) were found to have strong effects on inhibiting the aggregation of Aβ42 and reducing the toxicity of Aβ42 secreted by SH-SY5Y cells, including cell death, reactive oxygen species (ROS) production, and apoptosis.

Abstract Quorum sensing (QS) inhibition has emerged as a promising target for directed drug design, providing an appealing strategy for developing antimicrobials, particularly against infections caused by drug‐resistant pathogens. In this study, we designed and synthesized a total of 33 β‐nitrostyrene derivatives using 1‐nitro‐2‐phenylethane (NPe) as the lead compound, to target the facultative anaerobic bacterial pathogen Serratia marcescens. The QS‐inhibitory effects of these compounds were evaluated using S. marcescens NJ01 and the reporter strain Chromobacterium violaceum CV026. Among the 33 new β‐nitrostyrene derivatives, (E)‐1‐methyl‐4‐(2‐nitrovinyl)benzene (m‐NPe, compound 28) was proven to be a potent inhibitor that reduced biofilm formation of S. marcescens NJ01 by 79%. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) results revealed that treatment with m‐NPe (50 μg/ml) not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%. m‐NPe (50 μg/ml) decreased virulence factors in S. marcescens NJ01, reducing the activity of protease, prodigiosin, and extracellular polysaccharide (EPS) by 36%, 72%, and 52%, respectively. In S. marcescens 4547, the activities of hemolysin and EPS were reduced by 28% and 40%, respectively, outperforming the positive control, vanillic acid (VAN). The study also found that the expression levels of QS‐ and biofilm‐related genes (flhD, fimA, fimC, sodB, bsmB, pigA, pigC, and shlA) were downregulated by 1.21‐ to 2.32‐fold. Molecular dynamics analysis showed that m‐NPe could bind stably to SmaR, RhlI, RhlR, LasR, and CviR proteins in a 0.1 M sodium chloride solution. Importantly, a microscale thermophoresis (MST) test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor (QSI) against S. marcescens. Overall, this study highlights the efficacy of m‐NPe in suppressing the virulence factors of S. marcescens, identifying it as a new potential QSI and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.

This study addresses the issue of unstable flow in large-scale annular linear induction pumps (ALIPs), with a focus on optimizing their design and enhancing performance. Utilizing the ALIP model developed by Toshiba Corporation as a reference, the design process employs the equivalent circuit method to improve the hydraulic performance of high-flow ALIP systems. A comparison of various hydraulic and excitation structure parameters facilitated the identification of an optimal design scheme. A numerical simulation of the ALIP’s internal magneto-fluid coupling field was then conducted, based on magnetohydrodynamic (MHD) theory. The simulation results were validated against experimental data, confirming the model’s accuracy. Further simulations under various operational conditions were performed to analyze the distribution and magnitude of the axial Lorentz force (FL) and the axial pressure gradient across different flow rates and currents. The analysis indicated that the unstable flow primarily results from inverse pressure gradients, which are caused by the uneven distribution of these forces. To mitigate this issue, the study proposes the addition of a regulating coil winding to the inner stator. This addition significantly reduces the uneven distribution of magnetic fields and pressure gradients. These coils generate a compensating magnetic field that enhances FL within the electromagnetic section, thereby improving the axial force on the magnetic fluid. The results demonstrate that this active regulation method markedly reduces unsteady flow phenomena, stabilizes fluid movement, and offers a novel design strategy for large-scale ALIP systems. The ratio of the area of the regulating coils to that of the driving coils is only 0.33, which minimally increases the pump dimension. Additionally, the energy conversion rate of different regulation currents between the inner and outer regulation coils was compared. It was found that variations in the regulation current alter the total efficiency of the ALIP by no more than 1%, indicating that the control coil winding consumes minimal energy and that the stability of the magnetic fluid can be effectively controlled, making this approach feasible for engineering applications.

6-PPD quinone (6-PPDQ) is extensively existed in various environments. In Caenorhabditis elegans, exposure to 6-PPDQ could cause multiple toxic effects. In the current study, we further used C. elegans to investigate the effect of paeoniflorin (PF) treatment on 6-PPDQ toxicity and accumulation and the underlying mechanism. Treatment with PF (25–100 mg/L) inhibited 6-PPDQ toxicity on reproduction capacity and locomotion behavior and in inducing reactive oxygen species (ROS) production. Additionally, PF (25–100 mg/L) alleviated the dysregulation in expression of genes governing oxidative stress caused by 6-PPDQ exposure. Moreover, PF (25–100 mg/L) inhibited the enhancement in intestinal permeability caused by 6-PPDQ exposure and the accumulation of 6-PPDQ in the body of nematodes. In 6-PPDQ exposed nematodes, PF (25–100 mg/L) increased expression of acs-22 encoding a fatty acid transporter. RNAi of acs-22 could inhibit the beneficial effect of PF against 6-PPDQ toxicity in decreasing reproductive capacity and locomotion behavior, in inducing intestinal ROS production, and in enhancing intestinal permeability. RNAi of acs-22 could also suppress the PF beneficial effect against 6-PPDQ accumulation in the body of nematodes. Therefore, our results demonstrate the function of PF treatment against 6-PPDQ toxicity and accumulation in nematodes by activating the ACS-22.

Abstract MeFtsZ2-1 is a key gene for plant plastid division, but the mechanism by which MeFtsZ2-1 affects pigment accumulation in cassava (Manihot esculenta Crantz) through plastids remains unclear. We found that MeFtsZ2-1 overexpression in cassava (OE) exhibited darker colors of leaves, with increased levels of anthocyanins and carotenoids. Further observation via Transmission Electron Microscopy (TEM) revealed no apparent defects in chloroplast structure but an increase in the number of plastoglobule in OE leaves. RNA-seq results showed 1582 differentially expressed genes (DEGs) in leaves of OE. KEGG pathway analysis indicated that these DEGs were enriched in pathways related to flavonoid, anthocyanin, and carotenoid biosynthesis. This study reveals the role of MeFtsZ2-1 in cassava pigment accumulation from a physiological and transcriptomic perspective, providing a theoretical basis for improving cassava quality.

The strength and plasticity of 10B38 boron containing cold heading steel under different high temperature condi⁃ tions were studied using high-temperature tensile testing method. The results showed that the tensile strength decreased significantly from 124. 8 MPa to 22. 9 MPa at temperatures ranging from 700 to 950 ℃； At 950 to 1 150 ℃， the tensile strength was 12. 7 to 25. 5 MPa. In terms of thermoplastic properties， the cross-sectional shrinkage rate at 700-750 ℃ was 56%-72%； When the temperature was between 800 and 1 050 ℃， the cross-sectional shrinkage rate was ≥ 75%； When the temperature was between 1 050 and 1 150 ℃， the cross-sectional shrinkage rate was greater than 65%. Based on the above experimental data， the strength of the secondary cooling water in continuous casting was optimized from a specific water content of 1. 35 L/kg to a specific water content of 1. 25 L/kg. After optimization， the crack index of the continuous casting slab was significantly reduced. The dynamic CCT curves of 10B38 boron containing cold heading steel were mea⁃ sured， The experimental results showed that when the cooling rate was 0. 2-1 ℃/s， the test steel was mainly composed of softer ferrite structure； When the cooling rate was 3-10 ℃/s， the experimental steel was mainly composed of pearlite struc⁃ ture； When the cooling rate was 20 ℃/s and 30 ℃/s， the structure of the test steel was flat noodles martensite+pearlite； When the cooling rate was 50 ℃/s， a complete martensitic structure was formed at room temperature. The experimental re⁃ sults showed that by reducing the cooling rate to 0. 5-2 ℃/s， ideal ferrite and pearlite hot-rolled structures can be obtained.

Bisphenol S (BPS) is widely presented and affects aging with unclear mechanisms. Here, we applied C. elegans to evaluate the effects of BPS on lifespan and healthspan and to investigate the underlying mechanisms. Both early-life and whole-life exposure to BPS at environmentally relevant doses (0.6, 6, 60 μg/L) significantly decreased lifespan, and healthspan (body bend, pharyngeal pumping, and lipofuscin accumulation). BPS exposure impaired mitochondrial structure and function, which promoted ROS production to induce oxidative stress. Furthermore, BPS increased expressions of the insulin/IGF-like signaling (IIS). Also, BPS inhibited expression of the IIS transcription factor daf-16 and its downstream anti-oxidative genes. Quercetin effectively improved BPS-induced oxidative stress byreversing BPS-regulated IIS/daf-16 pathway and anti-oxidative gene expressions. In daf-2 and daf-16 mutants, the effects of BPS and quercetin on lifespan, healthspan, oxidative stress, and anti-oxidative genes expressions were reversed, demonstrating the requirement of IIS/daf-16 for aging regulation. Molecular docking and molecular dynamics simulations confirmed the stable interaction between DAF-2 and BPS mainly via three residues (VAL1260, GLU1329, and MET1395), which was attenuated by quercetin. Our results highlighted that adverse effects of BPS on impairing lifespan and healthspan by affecting IIS/daf-16 function against mitochondrial stress, which could be inhibited by quercetin treatment. Thus, we first revealed the underlying mechanisms of BPS-induced aging and the potential treatment.

Abstract Background Summarizing the clinical features of children with intussusception secondary to small bowel tumours and enhancing awareness of the disease. Methods Retrospective summary of children with intussusception admitted to our emergency department from January 2016 to January 2022, who underwent surgery and were diagnosed with small bowel tumours. Summarize the types of tumours, clinical presentation, treatment, and prognosis. Results Thirty-one patients were included in our study, 24 males and 7 females, with an age of onset ranging from 1 m to 11y 5 m. Post-operative pathology revealed 4 types of small intestinal tumour, 17 lymphomas, 10 adenomas, 4 inflammatory myofibroblastomas and 1 lipoma. The majority of tumours in the small bowel occur in the ileum (83.9%, 26/31). Abdominal pain, vomiting and bloody stools were the most common clinical signs. Operative findings indicated that the small bowel (54.8%, 17/31) and ileocolic gut were the main sites of intussusception. Two types of procedure were applied: segmental bowel resection (28 cases) and wedge resection of mass in bowel wall (3 cases). All patients recovered well postoperatively, with no surgical complications observed. However, the primary diseases leading to intussusception showed slight differences in long-term prognosis due to variations in tumor types. Conclusions Lymphoma is the most common cause of intussusception in pediatric patients with small bowel tumours, followed by adenoma. Small bowel tumours in children tend to occur in the ileum. Therefore, the treatment of SBT patients not only requires surgeons to address symptoms through surgery and obtain tissue samples but also relies heavily on the expertise of pathologists for accurate diagnosis. This has a significant impact on the overall prognosis of these patients.

Abstract Background Sparganosis is a worldwide food-borne parasitic disease caused by spargana infection, which infects the muscle of frogs and snakes as well as many tissues and organs in humans. There are currently no viable treatments for sparganosis. Understanding spargana’s nutrition source and carbohydrate metabolism may be crucial for identifying its energy supply and establishing methods of treatment for sparganosis. Methods Using an amino acid analyzer and nutrient concentration detection kits, we assessed nutrient concentrations in the muscles of Fejervarya limnocharis and Pelophylax plancyi infected or not infected with spargana. Quantitative polymerase chain reaction (PCR) was used to quantify the major enzymes involved in five glucose metabolism pathways of spargana developing in vivo. We also used quantitative PCR to assess key enzymes and transcriptome sequencing to explore the regulation of carbohydrate metabolic pathways in vitro in response to different 24-h food treatments. Results Infected muscle tissues had considerably higher concentrations of glucogenic and/or ketogenic amino acids, glucose, and glycogen than non-infected muscle tissues. We discovered that the number of differentially expressed genes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was larger in low-glucose than in other dietary groups. We examined differences in the expression of genes producing amino acid transporters, glucose transporters, and cathepsins in spargana grown in various nutritional environments. In the normal saline group, only the major enzymes in the tricarboxylic acid cycle (TCA), glycogenesis, and glycogenolysis pathways were expressed. The l-glutamine group had the greatest transcriptional levels of critical rate-limiting enzymes of gluconeogenesis and glycogenesis. Furthermore, the low-glucose group had the highest transcriptional levels of critical rate-limiting enzymes involved in the TCA, glycolytic, and glycogenolysis pathways. Surprisingly, when compared to the in vitro culturing groups, spargana developing in vivo exhibited higher expression of these critical rate-limiting enzymes in these pathways, with the exception of the pentose phosphate pathway. Conclusions Spargana have a variety of nutritional sources, and there is a close relationship between nutrients and the carbohydrate metabolism pathways. It takes a multi-site approach to block nutrient absorption and carbohydrate metabolism pathways to provide energy to kill them. Graphical Abstract

Abstract Motivated by hydraulic stimulation of enhanced geothermal systems, the present paper investigates the coupled thermo-hydro-mechanical response of a geothermal well imbedded in a thermoporoelastic medium, subjected to a non-isothermal fluid flux and convective cooling on the borehole surface. Our focus centers on the effect of local thermal non-equilibrium (LTNE) on the temporal-spatial evolution of temperatures, pore pressure, and stresses, where the solid and fluid phases have two distinct temperatures and local heat transfer between the two phases is addressed. We employ integral transform and load decomposition techniques to derive analytical solutions in the Laplace domain. This methodology allows us to disentangle and separate the individual contributions to changes in pore pressure and stresses from fluid injection and convective heat transfer. The results reveal that compared to the classical local thermal equilibrium model, the thermally induced pore pressure is slightly lower under LTNE conditions. The LTNE has a significant influence on the temporal evolution of thermally induced stresses, especially in the vicinity of the wellbore.

Background/Objectives: Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, distinguished by the impairment of the intestinal epithelial barrier, dysregulation of the gut microbiota, and abnormal immune responses. Cajanus cajan (L.) Millsp., traditionally used in Chinese herbal medicine for gastrointestinal issues such as bleeding and dysentery, has garnered attention for its potential therapeutic benefits. However, its effects on IBD remain largely unexplored. Methods: In this study, the major compounds from Cajanus cajan leaf extract (CCLE) were initially characterized by LCMS-IT-TOF. The IBD model was developed in C57BL/6 mice by administering continuous 4% (w/v) dextran sodium sulfate (DSS) aqueous solution over a period of seven days. The body weight, colon length, disease activity index (DAI), and histopathological examination using hematoxylin and eosin (H&E) staining were performed in the IBD model. The levels of the main inflammatory factors, specifically TNF-α, IL-1β, IL-6, and myeloperoxidase (MPO), were quantified by employing enzyme-linked immunosorbent assay (ELISA) kits. Additionally, the levels of tight junction proteins (ZO-1, Occludin) and oxidative stress enzymes (iNOS, SOD1, CAT) were investigated by qPCR. Subsequently, flow cytometry was employed to analyze the populations of various immune cells within the spleen, thereby assessing the impact of the CCLE on the systemic immune homeostasis of IBD mice. Finally, 16S rDNA sequencing was conducted to examine the composition and relative abundance of gut microbiota across different experimental groups. In addition, molecular docking analysis was performed to assess the interaction between the principal components of CCLE and the aryl hydrocarbon receptor (AHR). Results: We identified seven bioactive compounds in CCLE: catechin, cajachalcone, 2-hydroxy-4-methoxy-6-(2-phenylcinyl)-benzoic acid, longistylin A, longistylin C, pinostrobin, amorfrutin A, and cajaninstilbene acid. Our results demonstrated that oral administration of CCLE significantly alleviates gastrointestinal symptoms in DSS-induced IBD mice by modulating the balance of gut-derived pro- and anti-inflammatory cytokines. This modulation is associated with a functional correction in M1/M2 macrophage polarization and the Th17/Treg cell balance in splenic immune cells, as well as shifts in the populations of harmful bacteria (Erysipelatoclostridium and Staphylococcus) and beneficial bacteria (Odoribacter, unidentified Oscillospiraceae, Lachnoclostridium, and Oscillibacter) in the gut. Furthermore, cajaninstilbene acid, longistylin A, and longistylin C were identified as potential AhR agonists. Conclusions: The present results suggested that CCLE, comprising stilbenes like cajaninstilbene acid, longistylin A, and longistylin C, protects the epithelial barrier’s structure and function against DSS-induced acute IBD by restoring gut microbiota balance and systemic immune response as AhR agonists. Overall, CCLE represents a promising natural product-based therapeutic strategy for treating IBD by restoring gut microbiota balance and modulating systemic immune responses.

Fourier ptychography (FP) can break through the limitations of existing optical systems with a single aperture and realize large field-of-view (FOV) and high-resolution (HR) imaging simultaneously by aperture synthesis in the frequency domain. The method has potential applications for remote sensing and space-based imaging. However, the aperture stop of the imaging system was generally set to be much smaller than the system with an adjustable diaphragm, so it failed to make full use of the imaging capability of the system. In this paper, a reflective remote FP with full aperture is proposed, and the optical aperture of the camera is set to be the maximum according to the sample-matching condition, which can further improve the imaging resolution by exploring the whole capability of the system. Firstly, the physical model of the remote FP is established using oblique illumination of a convergent spherical wave. Then, the sampling characteristics of the low-resolution (LR) intensity image are analyzed. Assuming diffraction-limited imaging, the size of the aperture of the optical system needs to match the sampling of the detector. An experimental setup with an imaging distance of 2.4 m is built, and a series of LR images is collected by moving the camera for the diffused samples, including the USAF resolution test target and the banknote, where the diameter of the single aperture is set to the maximum to match the size of the CCD pixel under the practical minimum F# of the camera of 2.8. The high-resolution image is reconstructed by applying the iterative phase retrieval algorithm. The experimental results show that the reconstructed resolution is improved to 2.5×. This verifies that remote FP with full aperture can effectively improve the imaging resolution using only the present single-aperture optical system.

Protocatechuic acid (PCA) and protocatechuic aldehyde (PAL) are important phenolic compounds in plants. We here investigated their possible beneficial effect against fungal infection and the underlying mechanism. The model animal of Caenorhabditis elegans was used as host, and Candida albicans was used as fungal pathogen. The nematodes were first infected with C. albicans, and the PCA and PAL treatment were then performed. Post-treatment with 10–100 μM PCA and PAL suppressed toxicity of C. albicans infection in reducing lifespan. Accompanied with this beneficial effect, treatment with 10–100 μM PCA and PAL inhibited C. albicans accumulation in intestinal lumen. In addition, treatment with 10–100 μM PCA and PAL suppressed the increase in expressions of antimicrobial genes caused by C. albicans infection. The beneficial effect of PCA and PAL against C. albicans infection depended on p38 MAPK and insulin signals. Moreover, although treatment with 10–100 μM PCA and PAL could not exhibit noticeable antifungal activity, PCA and PAL treatment obviously suppressed biofilm formation, inhibited hyphal growth, and reduced expressions of virulence genes (ALS3, CaVps34, Vma7, Vac1, and/or HWP1) related to biofilm formation and hyphal growth in C. albicans. Therefore, our data demonstrated the potential of PCA and PAL post-treatment against fungal infection and fungal virulence.

In order to increase the scalability and reduce the complexity of photonic multipath SIC systems, a photonic multipath self-interference cancellation (SIC) method based on optical frequency comb (OFC) is proposed. The OFC is generated by continuously frequency-shifting the seed laser in the re-circulating frequency shifter (RFS) loop. The reference signal is modulated to the multiple combs of the OFC via a Mach-Zehnder modulator (MZM), and the received signal is loaded into another MZM. These two MZMs work at opposite quadrature bias points to reverse the phase of the received signal and the reference signal. After splitting and filtering with a dense wavelength division multiplexer, the reference modulation signals are injected into a multipath amplitude-delay matched link, where the amplitude and delay time are accurately controlled by several sets of optical variable attenuators and tunable delay lines. Both the inversion and amplitude-delay matching of the reference signals are realised in the optical domain, contributing to a broad bandwidth and high operational frequency. Experimental results show that the cancellation depth is greater than 45.9 dB for single-frequency signals, and 23.9 dB for signals with a bandwidth of 100 MHz in a setup with three self-interference paths. The proposed method is characterized by easy scalability, good flexibility, and low cost, making it suitable for complex multipath SIC in in-band full-duplex wireless systems.

A photonic method for the reconfigurable generation of switchable multi-format linearly frequency modulated (LFM) signal using a dual-polarization dual-parallel Mach-Zehnder modulator (DP-DPMZM) is proposed and experimentally verified. By properly controlling the bias voltage applied on the DP-DPMZM, different chirp waveforms, including dual-chirped, down-chirped and up-chirped LFM signals, can be obtained when a radio frequency (RF) signal and a baseband chirped signal are injected into the modulator. Besides, the central frequency of the generated LFM signal can be converted from X-band to K-band by adopting -2nd-order sideband instead of -1st-order sideband of the modulated RF signal. Moreover, the RF signal is always single sideband modulated, thus eliminating the dispersion-induced power fading, which is essential for the photonics-based distributed multi-function radar. In the proposed scheme, no optical filter is required, which also improves the stability and feasibility of the system.

N6-methyladenosine (m6A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m6A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m6A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m6A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m6A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m6A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m6A levels across different models of neurodegenerative disease, particularly Alzheimer’s disease and Parkinson’s disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m6A levels observed in Parkinson’s disease models exposed to manganese compared to normal Parkinson’s disease models further underscore the complexity of m6A’s role in neurodegenerative processes. The roles of m6A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the time-specific nature of m6A and its varying effects on distinct brain regions and in different environments.

Alzheimer’s disease (AD) is an intractable and progressive neurodegenerative disease. Amyloid beta (Aβ) aggregation is the hallmark of AD. Aβ induces neurotoxicity through a variety of mechanisms, including interacting with membrane receptors to alter downstream signaling, damaging cellular or organelle membranes, interfering with protein degradation and synthesis, and inducing an excessive immune-inflammatory response, all of which lead to neuronal death and other pathological changes associated with AD. In this study, we extracted gene expression profiles from the GSE5281 and GSE97760 microarray datasets in the GEO (Gene Expression Omnibus) database, as well as from the Human Gene Database. We identified differentially expressed genes in the brain tissues of AD patients and healthy persons. Through GO, KEGG, and ROC analyses, annexin A2 (AnxA2) was identified as a putative target gene. Notably, accumulating evidence suggests that intracellular AnxA2 is a key regulator in various biological processes, including endocytosis, transmembrane transport, neuroinflammation, and apoptosis. Thus, we conducted a series of cell biology experiments to explore the biological function of AnxA2 in AD. The results indicate that AnxA2 gene knockdown primarily affects oxidative phosphorylation, cell cycle, AD, protein processing in the endoplasmic reticulum, SNARE interactions in vesicular transport, and autophagy. In SH-SY5Y cells secreting Aβ42, AnxA2 gene knockdown exacerbated Aβ42-induced cytotoxicity, including cell death, intracellular ROS levels, and neuronal senescence, altered cell cycle, and reduced ATP levels, suggesting its critical role in mitochondrial function maintenance. AnxA2 gene knockdown also exacerbated the inhibitory effect of Aβ42 on cell migration. AnxA2 overexpression reduced the inflammatory response induced by Aβ42, while its absence increased pro-inflammatory and decreased anti-inflammatory responses. Furthermore, AnxA2 gene knockdown facilitated apoptosis and decreased autophagy. These results indicated potential pathophysiological roles of AnxA2 in AD.

Using Caenorhabditis elegans as animal model, we investigated the effect of exposure to polystyrene nanoparticles (PS-NPs) in the range of μg/L on high glucose toxicity induction. With lifespan and locomotion behavior as endpoints, we observed that PS-NP (10 and 100 μg/L) enhanced toxicity in 50 mM glucose treated animals. In insulin signaling pathway, expressions of genes encoding insulin receptor (daf-2), kinases (age-1 and akt-1/2), and insulin peptides (ins-9, ins-6, and daf-28) were increased, and expressions of daf-16 and its target of sod-3 were decreased in high glucose treated nematodes followed by PS-NP exposure. Toxicity enhancement in high glucose treated nematodes by PS-NP exposure was inhibited by RNAi of daf-2, age-1, akt-2, akt-1, and 3 insulin peptides genes, but increased by RNAi of daf-16 and sod-3. The resistance of animals with RNAi of daf-2 to toxicity in high glucose treated nematodes followed by PS-NP exposure could be suppressed by RNAi of daf-16. Moreover, in high glucose treated animals followed by PS-NP exposure, daf-2 expression was inhibited by RNAi of ins-6, ins-9, and daf-28. Our data demonstrated the risk of PS-NP exposure in enhancing the high glucose toxicity. More importantly, alteration in expression of genes in insulin signaling pathway was associated with the toxicity enhancement in high glucose treated nematodes followed by PS-NP exposure.

Increasing evidence has suggested that nanoplastic pollution has become a global concern. More importantly, transgenerational toxicity can be induced by nanoplastics at predicted environmentally relevant doses (ERDs). Considering that amino modification could increase nanoplastic toxicity, we compared transgenerational neurotoxicity between pristine polystyrene nanoparticle (PS-NP) and amino-modified PS-NP (NH2-PS-NP) in Caenorhabditis elegans. At 0.1–10 μg/L, NH2-PS-NP caused more severe transgenerational toxicity on locomotion and neuronal development. Accompanied with a difference in transgenerational neuronal damage, compared to PS-NP (10 μg/L), NH2-PS-NP (10 μg/L) induced more severe transgenerational activation of mec-4, crt-1, itr-1, and tra-3, which are required for the induction of neurodegeneration. Moreover, NH2-PS-NP (10 μg/L) caused more severe transgenerational inhibition in expressions of mpk-1, jnk-1, dbl-1, and daf-7 than PS-NP (10 μg/L), and RNA interference (RNAi) of these genes conferred susceptibility to the toxicity of PS-NP and NH2-PS-NP on locomotion and neuronal development. NH2-PS-NP (10 μg/L) further caused more severe transgenerational activation of germline ligand genes (ins-3, ins-39, daf-28, lin-44, egl-17, efn-3, and lag-2) than PS-NP (10 μg/L), and RNAi of these ligand genes caused resistance to the toxicity of PS-NP and NH2-PS-NP on locomotion and neuronal development. Our results highlighted more severe exposure risk of amino-modified nanoplastics at ERDs in causing transgenerational neurotoxicity in organisms.

Transgenerational nanoplastic toxicity could be detected in Caenorhabditis elegans after exposure at the parental generation (P0-G); however, the underlying mechanisms remain largely unclear. We aimed to examine the role of germline nuclear hormone receptors (NHRs) in controlling the transgenerational toxicity of polystyrene nanoparticles (PS-NPs) based on gene expression screening and functional analysis. Among germline NHR genes, daf-12, nhr-14, and nhr-47 expressions were increased and nhr-12 expression was decreased by PS-NPs (1 and 10 μg/L). Transgenerational alterations in expressions of these four NHR genes were also induced by PS-NPs (1 and 10 μg/L). RNAi of daf-12, nhr-14, and nhr-47 caused resistance, whereas RNAi of nhr-12 conferred susceptibility to transgenerational PS-NP toxicity. After PS-NP exposure, expressions of ins-3, daf-28, and ins-39 encoding insulin ligands, efn-3 encoding Ephrin ligand, and lin-44 encoding Wnt ligand, as well as expressions of their receptor genes (daf-2, vab-1, and/or mig-1), were dysregulated by the RNAi of daf-12, nhr-14, nhr-47, and nhr-12. Therefore, alteration in certain germline NHRs could mediate the induction of transgenerational nanoplastic toxicity by affecting secreted ligands and their receptors in the offspring of exposed organisms.

Alzheimer’s disease (AD) is a neurodegenerative disease. Mitochondrial energy metabolism and p70 ribosomal protein S6 kinase (p70S6K) play significant roles in AD pathology. However, the potential relationship between them is unclear. In this study, bioinformatics methods were initially applied to analyze the transcriptomic data in the CA1 and the primary visual cortex of patients with AD and Aβ42-treated SH-SY5Y cells. By applying secreted Aβ42 and p70S6K gene silencing in cells, we explored disorders in mitochondrial function and the regulatory roles of p70S6K by flow cytometry, laser scanning confocal microscopy, high-performance liquid chromatography, Western blotting, and quantitative reverse transcription PCR. The study reveals that impaired mitochondrial energy metabolism is a potential pathological feature of AD and that p70S6K gene silencing reversed most of the changes induced by Aβ42, such as the activities of the electron transport chain complexes I and III, as well as ATP synthase, ATP production, generation of reactive oxygen species, mitochondrial membrane potential, and phosphorylation of AMPK, PINK1, and Parkin, all of which are required for mitochondria to function properly in the cell.

Abstract Heat shock proteins are important molecular chaperones that are involved in plant growth and stress responses. However, members of the Hsp family have been poorly studied in cassava. In this study, 225 MeHsp genes were identified in the cassava genome, and their genetic structures exhibited relatively conserved features within each subfamily. The 225 MeHsp genes showed random chromosomal distribution, and at least 74 pairs of segmentally duplicated MeHsp genes. Eleven tandemly duplicated MeHsp genes were identified. Cis‐element analysis revealed the importance of MeHsps in plant adaptations to the environment. The prediction of protein interactions suggested that MeHsp70‐20 may play a critical regulatory role in the interactive network. Furthermore, the expression profiles of MeHsps in different tissues and cell subsets were analyzed using bulk transcriptomics and single‐cell transcriptomic data. Several subfamily genes exhibited unique expression patterns in the transcriptome and were selected for detailed analysis of the single‐cell transcriptome. Quantitative real‐time polymerase chain reaction (qRT‐PCR) revealed the expression patterns of these genes under temperature stress, further supporting the prediction of cis‐acting elements. This study provides valuable information for understanding the functional characteristics of MeHsp genes and the evolutionary relationships between MeHsps.

Breast cancer is one of the leading causes of cancer mortality. Breast cancer patients in developing countries, especially sub-Saharan Africa, South Asia, and South America, suffer from the highest mortality rate in the world. One crucial factor contributing to the global disparity in mortality rate is long delay of diagnosis due to a severe shortage of trained pathologists, which consequently has led to a large proportion of late-stage presentation at diagnosis. To tackle this critical healthcare disparity, we have developed a deep learning-based diagnosis system for metastatic breast cancer that can achieve high diagnostic accuracy as well as computational efficiency and mobile readiness suitable for an under-resourced environment. We evaluated 4 Convolutional Neural Network (CNN) architectures: MobileNetV2, VGG16, ResNet50 and ResNet101. The MobileNetV2-based diagnostic model outperformed the more complex VGG16, ResNet50 and ResNet101 models in diagnostic accuracy, model generalization, and model training efficiency. The ROC AUC of MobilenetV2 (0.933, 95% CI: 0.930, 0.936) was higher than VGG16 (0.911, 95% CI: 0.908, 0.915), ResNet50 (0.869, 95% CI: 0.866, 0.873), and ResNet101 (0.873, 95% CI: 0.869, 0.876). The time per inference step for the MobileNetV2 model (15 ms/step) was substantially lower than that of VGG16 (48 ms/step), ResNet50 (37 ms/step), and ResNet110 (56 ms/step). The visual comparisons between the model prediction and ground truth have demonstrated that the MobileNetV2 diagnostic models can identify very small cancerous nodes embedded in a large area of normal cells which is challenging for manual image analysis. Equally Important, the light weight MobleNetV2 models were computationally efficient and ready for mobile devices or devices of low computational power. These advances empower the development of a resource-efficient and high performing AI-based metastatic breast cancer diagnostic system that can adapt to under-resourced healthcare facilities in developing countries.

Abstract Background This study aims to summarize our experience in diagnosis and treatment of pediatric duodenal ulcer perforation in a National Center for Children’s Health. Methods Fifty-two children with duodenal perforation hospitalized in Beijing Children’s Hospital Affiliated to Capital Medical University from January 2007 to December 2021 were retrospectively collected. According to the inclusion and exclusion criteria, patients with duodenal ulcer perforation were included in the group. They were divided into the surgery group and the conservative group according to whether they received surgery. Results A total of 45 cases (35 males and 10 females) were included, with a median age of 13.0 (0.3–15.4) years. Forty cases (40/45, 88.9%) were over 6 years old, and 31 (31/45, 68.9%) were over 12 years old. Among the 45 cases, 32 cases (32/45, 71.1%) were examined for Helicobacter pylori (HP), and 25 (25/32, 78.1%) were positive. There were 13 cases in the surgery group and 32 cases in the conservative group, without a significant difference in age between the two groups (P = 0.625). All cases in the surgery group and the conservative group started with abdominal pain. The proportion of history time within 24 h in the two groups was 6/13 and 12/32 (P = 0.739), and the proportion of fever was 11/13 and 21/32 (P = 0.362). The proportion of pneumoperitoneum in the surgery group was higher than that in the conservative group (12/13 vs. 15/32, P = 0.013). The fasting days in the surgery group were shorter than those in the conservative group (7.7 ± 2.92 vs. 10.3 ± 2.78 days, P = 0.014). There was no significant difference in the total hospital stay (13.6 ± 5.60 vs14.8 ± 4.60 days, P = 0.531). The operation methods used in the surgery group were all simple sutures through laparotomy (9 cases) or laparoscopy (4 cases). All patients recovered smoothly after surgery. Conclusion Duodenal ulcer perforation in children is more common in adolescents, and HP infection is the main cause. Conservative treatment is safe and feasible, but the fasting time is longer than the surgery group. A simple suture is the main management for the surgery group.

Nanoplastics and microbial pathogens are both widely distributed in the environment; however, their combined toxicity remains largely unclear. Using Caenorhabditis elegans as an animal model, we examined the possible effect of exposure to polystyrene nanoparticle (PS-NP) in Acinetobacter johnsonii AC15 (a bacterial pathogen) infected animals. Exposure to PS-NP at the concentrations of 0.1–10 μg/L significantly enhanced the toxicity of Acinetobacter johnsonii AC15 infection on lifespan and locomotion behaviors. In addition, after exposure to 0.1–10 μg/L PS-NP, the accumulation of Acinetobacter johnsonii AC15 in body of nematodes was also increased. Meanwhile, the innate immune response indicated by the increase of antimicrobial gene expressions in Acinetobacter johnsonii AC15 infected nematodes was suppressed by exposure to 0.1–10 μg/L PS-NP. Moreover, expressions of egl-1, dbl-1, bar-1, daf-16, pmk-1, and elt-2 governing the bacterial infection and immunity in Acinetobacter johnsonii AC15 infected nematodes were further inhibited by exposure to 0.1–10 μg/L PS-NP. Therefore, our data suggested the possible exposure risk of nanoplastic at predicted environmental concentrations in enhancing the toxic effects of bacterial pathogens on environmental organisms.

A Doppler velocity simulation method based on serrodyne modulation is proposed to achieve the frequency shift from hundred hertz to megahertz. One sub-phase modulation (PM) in a dual-parallel dual-drive Mach–Zehnder modulator loads a sawtooth signal to achieve a small frequency shift of the optical carrier. The other three sub-PMs implement carrier-suppressed double-band modulation of the RF signal. The RF signal is directly coupled from the receiving antenna to the modulator’s RF port without any electrical devices like a 90° hybrid, which ensures a broad operational bandwidth of the system. After filtering out one of the RF modulation sidebands by an optical filter, Doppler frequency shifting (DFS) is realized through frequency beating. The half-wave voltage of modulators rapidly decreases at low frequency shifts, leading to an increase in spurious signals. In order to improve the spurious suppression ratio (SSR) of DFS, a digital pre-distortion compensation based on the measured half-wave voltage is implemented in the frequency domain. Experimental results show that SSRs are larger than 35 dB when frequency shifts range from 0.1 kHz to 1 MHz. The RF operation bandwidth covers 2–40 GHz. The effectiveness of a Doppler velocity simulator is evaluated, and the simulation velocity error is less than 0.06 km/h. The proposed method has potential applications in both broadband electronic warfare and traffic metering applications.

The modulation of a terahertz (THz) wave on amplitude, phase and polarization is important for the application of THz technology, especially in the field of imaging, and is one of the current research hotspots. Silicon-based, optically excited THz modulator is a wavefront modulation technique with a simple, compact and reconfigurable optical path. It can realize the dynamic modulation of THz wavefronts by only changing the projected two-dimensional pattern, but it still suffers from the problems of lower modulation efficiency and slower modulation rates. In this article, the Drude model in combination with the multiple thin layers structure model and Fresnel matrix method is used to compare the modulation efficiencies of three modulation modes and more factors. The method is more accurate than the popular proposed method, especially when the thickness of the excited photoconductive layers reaches a few hundred microns. In comparing the three modes, namely transmission, ordinary reflection and total internal reflection, it is found the total internal reflection modulation mode has the best modulation efficiency. Further, under this mode, the effects of three factors, including the lifetime of photo-excited carriers, the wavelength of pump light and the frequency of THz wave, on the performance of THz modulator are analyzed. The simulation results show that the realization of total internal reflection using silicon prisms is a simple and effective method to improve the modulation efficiency of a silicon-based optically excited THz modulator, which provides references for the design of a photo-induced THz modulator.

This paper presents a C++ program named ALPHA MODEL as the pioneer software for modelling and analysis of hydrate-saturation-dependent permeability for hydrate-bearing porous media. ALPHA MODEL features a main graphical user interface (GUI) controlling program execution, display and output of data and results, and a few secondary GUIs for mathematical calculations. Users can use it to not only get the most applicable permeability model by running the fitting analysis module, but also deduce some properties (hydrate pore morphology and formation conditions) through direct visual display. ALPHA MODEL has been proved to be credible when applied to laboratory and natural samples.

In organisms, high glucose can cause several aspects of toxicity, including the lifespan reduction. Paeoniflorin is the major component of Paeoniaceae plants. Nevertheless, the possible effect of paeoniflorin to suppress high glucose toxicity in reducing lifespan and underlying mechanism are largely unclear. Thus, in this study, we examined the possible effect of paeoniflorin in suppressing high glucose (50 mM)-induced lifespan reduction and the underlying mechanism in Caenorhabditis elegans. Administration with 16–64 mg/L paeoniflorin could prolong the lifespan in glucose treated nematodes. Accompanied with this beneficial effect, in glucose treated nematodes, expressions of daf-2 encoding insulin receptor and its downstream kinase genes (age-1, akt-1, and akt-2) were decreased and expression of daf-16 encoding FOXO transcriptional factor was increased by 16–64 mg/L paeoniflorin administration. Meanwhile, the effect of paeoniflorin in extending lifespan in glucose treated nematodes was enhanced by RNAi of daf-2, age-1, akt-1, and akt-2 and inhibited by RNAi of daf-16. In glucose treated nematodes followed by paeoniflorin administration, the increased lifespan caused by daf-2 RNAi could be suppressed by RNAi of daf-16, suggesting that DAF-2 acted upstream of DAF-16 to regulate pharmacological effect of paeoniflorin. Moreover, in glucose treated nematodes followed by paeoniflorin administration, expression of sod-3 encoding mitochondrial Mn-SOD was inhibited by daf-16 RNAi, and the effect of paeoniflorin in extending lifespan in glucose treated nematodes could be suppressed by sod-3 RNAi. Molecular docking analysis indicated the binding potential of paeoniflorin with DAF-2, AGE-1, AKT-1, and AKT-2. Therefore, our results demonstrated the beneficial effect of paeoniflorin administration in inhibiting glucose-induced lifespan reduction by suppressing signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16-SOD-3 in insulin signaling pathway.