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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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In order to improve the hydraulic efficiency and internal flow pattern of a multi-stage pump under multiple flow conditions, an intelligent optimization design was proposed for its hydraulic components. Sensitivity analysis was used to select the key parameters influencing the hydraulic efficiency of a multi-stage pump. The optimal Latin hypercube sampling and non-dominated sorting genetic algorithm Ⅱ were employed to build a multi-objective optimization system. Moreover, a radial basis function neural network was adopted as the surrogate model of hydraulic efficiency. The research results showed that the impeller outlet width, impeller blade wrap angle, impeller outlet blade angle, and diffuser inlet width were the key factors affecting the hydraulic efficiency. The efficiency of the optimized model increased by 4.35% under the design condition and the matching of the internal flow between the optimized impeller and diffuser was significantly enhanced under the nominal condition. The improved flow pattern could be clearly observed in the flow passage of both the pump impeller and the diffuser. After optimization, the wear performance of the model was also improved compared to the original design. The wear area decreased in size and was distributed more evenly, resulting in a noticeable decrease in the maximum amount of wear.

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.

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.

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.

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.

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.

Paeoniflorin is one of the important components in Paeoniaceae plants. In this study, we used Caenorhabditis elegans as a model host and Pseudomonas aeruginosa as a bacterial pathogen to investigate the possible role of paeoniflorin treatment against P. aeruginosa infection in the host and the underlying mechanisms. Posttreatment with 1.25–10 mg/L paeoniflorin could significantly increase the lifespan of P. aeruginosa infected nematodes. After the infection, the P. aeruginosa colony-forming unit (CFU) and P. aeruginosa accumulation in intestinal lumen were also obviously reduced by 1.25–10 mg/L paeoniflorin treatment. The beneficial effects of paeoniflorin treatment in increasing lifespan in P. aeruginosa infected nematodes and in reducing P. aeruginosa accumulation in intestinal lumen could be inhibited by RNAi of pmk-1, egl-1, and bar-1. In addition, paeoniflorin treatment suppressed the inhibition in expressions of pmk-1, egl-1, and bar-1 caused by P. aeruginosa infection in nematodes, suggesting that paeoniflorin could increase lifespan of P. aeruginosa infected nematode by activating PMK-1, EGL-1, and BAR-1. Moreover, although treatment with 1.25–10 mg/L paeoniflorin did not show obvious anti-P. aeruginosa activity, the P. aeruginosa biofilm formation and expressions of related virulence genes (pelA, pelB, phzA, lasB, lasR, rhlA, and rhlC) were significantly inhibited by paeoniflorin treatment. Treatment with 1.25–10 mg/L paeoniflorin could further decrease the levels of related virulence factors of pyocyanin, elastase, and rhamnolipid. In addition, 2.5–10 mg/L paeoniflorin treatment could inhibit the swimming, swarming, and twitching motility of P. aeruginosa, and treatment with 2.5–10 mg/L paeoniflorin reduced the cyclic-di-GMP (c-di-GMP) level. Therefore, paeoniflorin treatment has the potential to extend lifespan of P. aeruginosa infected hosts by reducing bacterial accumulation in intestinal lumen and inhibiting bacterial biofilm formation.

Fenitrothion (FNT), an organophosphorus insecticide, is widely detected in the living environment. The reproductive and endocrine toxicity of FNT to biological communities has been ever reported, but potential mechanism and reproductive toxicity dose effect remain unclear. In our study, we constructed Caenorhabditis elegans model to analyze the reproductive toxicity mechanism of FNT based on metabolomics and evaluated its reproductive toxicity dose effect using benchmark dose (BMD)method. Our results showed that FNT exposure significantly reduced brood size, number of germ cells, and delayed gonadal development in nematodes. Non-targeted metabolomics revealed that FNT exposure caused significant metabolic disturbances in nematodes, leading to a significant reduction in the synthesis of cortisol and melatonin, and the latter played a mediating role in the effects of FNT on number of germ cells. We further found that the levels of these two hormones were significantly negative correlated with the expression of the androgen receptor nhr-69 and affected the meiosis of germ cells by regulating the nhr-69/ fbf-1/2 /gld-3 /fog-1/3 pathway. Meanwhile, the study found the BMDL10s for N2 and him-5 mutant were 0.411 μg/L by number of germ cells and 0.396 μg/L by number of germ cells in the meiotic zone, respectively, providing a more protective reference dose for ecological risk assessment of FNT. This study suggested that FNT can affect androgen receptor expression by inhibiting cortisol and melatonin secretion, which further mediate the meiotic pathway to affect sperm formation and exert reproductive toxicity, and provides a basis for setting reproductive toxicity limits for FNT.

Alzheimer’s disease (AD) is a neurodegenerative disease and the main pathological characteristic of AD is the deposition of Aβ42 in the brain. Inhibition of Aβ42 polymerization is one of the important research directions. Due to the pathological complexity of Alzheimer’s disease, studies on Aβ42 polymerization inhibitors have not made significant progress worldwide. Using an independently constructed structure database of oligopeptides, in this study, molecular docking, umbrella sampling analysis of free energy, ThT fluorescence detection of Aβ42 polymerization, transmission electron microscopy, and flow cytometry detection of reactive oxygen species (ROS) and apoptosis were performed to screen tripeptides and pentapeptides that inhibit polymerization. It was found that two tripeptides, i.e., WRR and ERW, bind stably to the core of Aβ42 polymerization in the molecular dynamics analysis, and they significantly inhibited the aggregation of Aβ42 and reduced their cell toxicity in vitro.

The absence of regional electrical data has constrained our comprehension of the deep geological structures in the Jizhong Depression. This limitation has impeded the exploration of factors and principles governing geothermal reservoirs. Historically, studies on these factors primarily centered on geothermal field attributes, such as anomalous geothermal flux, geothermal gradients, and deep Moho variations. In our research, we undertook an exhaustive interpretation of extended-period magnetotelluric readings. This was amalgamated with prior regional geological and geophysical studies to discern deep geological structural details pertinent to geothermal resource components, encompassing heat sources, pathways, reservoirs, and cap rocks. Our analysis spanned the foundational surface of the Cenozoic era, fault configurations, carbonate formation distribution, and layers with low velocity yet high conductivity. We also statistically evaluated geothermal wells, their density, and the water temperature attributes across various structural entities. This aided in comprehending how structural units influence thermal well features. Our research delineated the spatial interrelation between geothermal well distribution and deep geological structures, including carbonate rock distribution, Cenozoic thickness, fault patterns, and profound low-velocity, high-conductivity layers. Moreover, we scrutinized how structural unit types impact thermal well attributes, offering insights into the formation principles of deep carbonate geothermal reservoirs within the Jizhong Depression. Our findings suggest that the genesis of deep geothermal resources in the Jizhong Depression is swayed by regional geological conditions. Notably, the distribution of regional and especially deep geothermal wells is intimately tied to regional stratigraphy, structural designs, and profound geological structural traits. Furthermore, the temperature within geothermal wells correlates strongly with the burial depth, carbonate formation thickness, Cenozoic thickness, and proximity to fault channels responsible for fluid movement and heat transmission.

By analyzing Soil Moisture Anomaly Percentage Index （SMAPI） at different soil layers， dry-wet evolution of the source region of the Yellow River （SRYR） during 2008 -2017 are investigated using observations from the Maqu-Ruoergai soil temperature and moisture monitoring network.To diagnose the water vapor transportation path and potential water vapor sources in different processes， the Lagrange Flexible Particle Dispersion Model （FLEXPART）， which is driven by reanalysis data （National Centers for Environmental Prediction Final， NECP FNL）， are used to simulate the backward trajectories of target particles.The results show that the water vapor transportation path can be divided into three categories： （1） South Branch transportation.The water vapor origins from the Indian Ocean and the Arabian Sea， and finally arrives at the SRYR by way of the Indian Peninsula and Bay of Bengal； （2） East Branch transportation.The water vapor is from the Pacific Ocean and the South China Sea， then passes through the Yangtze River Basin， and finally arrives at the SRYR from eastern and southern flank of the Tibetan Plateau； （3） North Branch transportation.The water vapor is from the Atlantic Ocean， the northern African continent， and the European continent， then arrives at the SRYR from the western or northern side of the Tibetan Plateau by way of the mid-latitude Eurasian continent.Moreover， the North Branch is dominant in dry period， whereas the South and East branches are prominent in wet period.The water vapor sources also show discrepancies for dry and wet periods.The water vapor sources of the Tibetan Plateau are mainly distributed around the Kunlun Mountains during wet period， and are scattered distributed from north to south during transitional period， and are located around the Tianshan during dry period.The intensity of the water vapor sources of the Iranian Plateau， Pamir Plateau， and the Bay of Bengal gradually strengthen from wet to dry period， the intensity of the water vapor sources of the Sichuan Basin-Qinling Mountains and south China enhanced first and then weakened， while the source of Qilian Mountain-Loess Plateau weakened after enhanced.The intensity of water vapor sources over the middle and lower reaches of the Yangtze River and around East China has been weakening from the wet period to the dry period.

IntroductionSingle-cell transcriptome sequencing (ScRNA-seq) has emerged as an effective method for examining cell differentiation and development. In non-model plants, it hasn't been employed very much, especially in sink organs that are abundant in secondary metabolites.ResultsIn this study, we sequenced the single-cell transcriptomes at two developmental phases of cassava tuberous roots using the technology known as 10x Genomics (S1, S2). In total, 14,566 cells were grouped into 15 different cell types, primarily based on the marker genes of model plants known to exist. In the pseudotime study, the cell differentiation trajectory was defined, and the difference in gene expression between the two stages on the pseudotime axis was compared. The differentiation process of the vascular tissue and cerebral tissue was identified by the trajectory. We discovered the rare cell type known as the casparian strip via the use of up-regulated genes and pseudotime analysis, and we explained how it differentiates from endodermis. The successful creation of a protoplast isolation technique for organs rich in starch was also described in our study.DiscussionTogether, we created the first high-resolution single-cell transcriptome atlas of cassava tuberous roots, which made significant advancements in our understanding of how these roots differentiate and develop.

Atrazine (ATR), a widely used triazine herbicide, is an environmental endocrine disruptor that can cause health problems. However, whether there are multi/trans-generational reproductive impacts of ATR have not been studied. Therefore, in this study, Caenorhabditis elegans was used as a preferable model organism to identify the multi/trans-generational reproductive toxicity of ATR. Only parental C.elegans (P0) were exposed to different concentrations (0.0004–40 mg/L) for 48 h and the subsequent offspring (F1–F5) were grown under ATR-free conditions and ATR conditions.The results showed that ATR exposure during P0 decreased fecundity, including a reduction in fertilized eggs, oocytes, and ovulation rate, delayed gonadal development, and decreased the relative area of gonad arm and germ cell number. Furthermore, continuous ATR exposure (P0–F5) causes a significant increase in reproductive toxicity in subsequent generations, although no significant toxicity occurred in the P0 generation after exposure to environmental-related concentrations, suggesting that ATR exposure might have cumulative effects. Likewise, parental exposure to ATR caused transgenerational toxicity impairments. Interestingly, only reproductive toxicity, not development toxicity, was transmitted to several generations (F1–F4), and the F2 generation showed the most notable changes. QRT-PCR results showed that genes expression related to DNA methylation 6 mA (damt-1, nmad-1) and histone H3 methylation (mes-4, met-2, set-25, set-2, and utx-1) can also be passed on to offspring. The function of H3K4 and H3K9 methylation were explored by using loss-of-function mutants for set-2, set-25, and met-2. Transmissible reproductive toxicity was absent in met-2(n4256), set-2(ok952), and set-25(n5021) mutants, which suggests that the histone methyltransferases H3K4 and H3K9 activity are indispensable for the transgenerational effect of ATR. Finally, the downstream genes of DNA methylation and histone H3 methylation were determined. ATR upregulated the expression of ZC317.7, hsp-6, and hsp-60. Mitochondrial stress in parental generation dependent transcription 6 mA modifiers may establish these epigenetic marks in progeny.

Qiang Huang et al. fed C. elegans with E. coli containing phosphorothioate (PT) DNA or a control strain and evaluated the impact on animal physiology. They observed that worms fed PT( + ) diets exhibited low reactive oxygen species, more active movement, and a longer lifespan compared to controls, suggesting that PT-DNA may have a positive effect on animal health.

Abstract Acinetobacter has been frequently detected in backwater areas of the Three Gorges Reservoir (TGR) region. We here employed Caenorhabditis elegans to perform biosafety assessment of Acinetobacter strains isolated from backwater area in the TGR region. Among 21 isolates and 5 reference strains of Acinetobacter, exposure to Acinetobacter strains of AC1, AC15, AC18, AC21, A. baumannii ATCC 19606T, A. junii NH88-14, and A. lwoffii DSM 2403T resulted in significant decrease in locomotion behavior and reduction in lifespan of Caenorhabditis elegans. In nematodes, exposure to Acinetobacter strains of AC1, AC15, AC18, AC21, A. baumannii, A. junii and A. lwoffii also resulted in significant reactive oxygen species (ROS) production. Moreover, exposure to Acinetobacter isolates of AC1, AC15, AC18, and AC21 led to significant increase in expressions of both SOD-3::GFP and some antimicrobial genes (lys-1, spp-12, lys-7, dod-6, spp-1, dod-22, lys-8, and/or F55G11.4) in nematodes. The Acinetobacter isolates of AC1, AC15, AC18, and AC21 had different morphological, biochemical, phylogenetical, and virulence gene properties. Our results suggested that exposure risk of some Acinetobacter strains isolated from the TGR region exists for environmental organisms and human health. In addition, C. elegans is useful to assess biosafety of Acinetobacter isolates from the environment.

Exposure to nanoplastics can induce toxicity on organisms at both parental generation (P0-G) and the offspring. However, the underlying mechanism remains unknown. Using Caenorhabditis elegans as a model organism, exposure to 20-nm polystyrene nanoparticle (PS-NP) (1–100 μg/L) upregulated the expressions of insulin ligands (INS-39, INS-3, and DAF-28), and this increase could be further detected in the offspring after PS-NP exposure. Germline ins-39, ins-3, and daf-28 RNAi induced resistance to transgenerational toxicity of PS-NP, indicating that increase in expression of these three insulin ligands mediated induction of transgenerational toxicity. These three insulin ligands transgenerationally activated function of insulin receptor DAF-2 to control transgenerational toxicity of PS-NP. Exposure to 1–100 μg/L PS-NP further upregulated DAF-2, AGE-1, and AKT-1 expressions and downregulated DAF-16 expression. During transgenerational toxicity control, DAF-16/AKT-1/AGE-1 was identified as downstream signaling cascade of DAF-2. Moreover, transcriptional factor DAF-16 activated two downstream targets of HSP-6 (a mitochondrial UPR marker) and SOD-3 (a mitochondrial SOD) to modulate transgenerational toxicity of PS-NP. Our findings indicate a crucial link between activation of insulin signaling and induction of transgenerational toxicity of nanoplastics at low concentrations in organisms.

A structure for joining thin-walled 6061-T6 aluminum alloy tube (outer tube) and Q195 steel tube (inner tube) by electromagnetic flanging process was proposed. The formation process, mechanical properties, failure modes, and morphology of the joint were investigated. The results showed that the outer tube impacted the inner tube, the flanges of the prefabricated holes on the outer tube were embedded into the prefabricated holes of the inner tube under the action of Lorentz force, and thus the mechanical locking joint was obtained. There were two tensile failure modes for the joints: Pull-out and fracture. Specifically, when the discharge energy was relatively high, the failure mode changed from pull-out to fracture. Combining the results of tensile tests and morphology observations, the maximum loads of the joints increased with the discharge energy. However, excessive discharge energy would lead to the brittle fracture of the inner tube, which was not beneficial to the service. Better discharge energy and the maximum load of the joint at this discharge energy were obtained.

Interfacial zones straddling terrestrial and marine realms, colloquially known as mudflats, epitomize a dynamic nexus between these environments and are fundamental to the coastal ecosystem. The investigation of these regions is paramount for facilitating infrastructural developments including ports, wharfs, cross-sea bridges, and the strategic utilization of freshwater resources sequestered from mainland islands amid ongoing economic progress. Terrestrial realms conventionally employ electromagnetic techniques as efficacious modalities to delineate subterranean geological information, encompassing structural details and water-bearing strata. However, the peculiar topographic and geological nuances of mudflat regions pose substantial challenges for the efficacious application of electromagnetic methodologies. The present paper endeavors to address these challenges by suggesting innovative modifications to the existing instrumentation and evolving novel data acquisition techniques specifically tailored for electromagnetic exploration within mudflat environments. This paper delves into the electrical characteristics of water-bearing layers within mudflats, and ascertains details pertaining to the subterranean structure and the spatial distribution of fresh and saline water resources, through the holistic interpretation of a multitude of profiles.

Recently, the transgenerational toxicity of nanoplastics has received increasing attention. Caenorhabditis elegans is a useful model to assess the transgenerational toxicity of different pollutants. In nematodes, the possibility of early-life exposure to sulfonate-modified polystyrene nanoparticle (PS-S NP) causing transgenerational toxicity and its underlying mechanisms were investigated. After exposure at the L1-larval stage, transgenerational inhibition in both locomotion behavior (body bend and head thrash) and reproductive capacity (number of offspring and fertilized egg number in uterus) was induced by 1–100 μg/L PS-S NP. Meanwhile, after exposure to 1–100 μg/L PS-S NP, the expression of germline lag-2 encoding Notch ligand was increased not only at the parental generation (P0-G) but also in the offspring, and the transgenerational toxicity was inhibited by the germline RNA interference (RNAi) of lag-2. During the transgenerational toxicity formation, the parental LAG-2 activated the corresponding Notch receptor GLP-1 in the offspring, and transgenerational toxicity was also suppressed by glp-1 RNAi. GLP-1 functioned in the germline and the neurons to mediate the PS-S NP toxicity. In PS-S NP-exposed nematodes, germline GLP-1 activated the insulin peptides of INS-39, INS-3, and DAF-28, and neuronal GLP-1 inhibited the DAF-7, DBL-1, and GLB-10. Therefore, the exposure risk in inducing transgenerational toxicity through PS-S NP was suggested, and this transgenerational toxicity was mediated by the activation of germline Notch signal in organisms.

BackgroundPrevious studies have shown that patients with acoustic neuroma (AN) sometimes present with sudden sensorineural hearing loss (SSNHL) as an initial symptom. The purpose of this research was to investigate the clinical characteristics, diagnosis, and treatment of AN in patients initially diagnosed with SSNHL.Materials and methodsWe reviewed retrospectively the medical records of all patients who were treated as SSNHL initially and were later diagnosed with AN after undergoing magnetic resonance imaging (MRI) at our hospital between 2008 and 2021. Patient demographics, associated complaints (mostly tinnitus and vertigo), the severity of hearing loss, audiogram configurations, auditory brainstem response (ABR), and MRI examination were reviewed and analyzed. In addition, treatment outcomes and management protocols were also included in this study.ResultsA total of 10 (0.7%, 10/1,383) patients presented with SSNHL as the initial symptom and were diagnosed as AN by MRI finally. Of the 10 patients enrolled in this study, four were men and six were women. The average age at the time of diagnosis of SSNHL was 46.2 ± 13.16 years. These patients exhibited varying severity of hearing loss and a variety of audiogram configurations. All patients showed an abnormal ABR. According to the Koos grading standard, there were 5 grade I (intracanalicular [IAC]) tumors, 3 grade II tumors, and 2 grade III tumors. The treatment outcome revealed that 2 patients exhibited recovery of the average hearing of impaired frequency by more than 15 dB, and 6 patients showed no recovery. Furthermore, four patients were referred to undergo surgical treatment after being diagnosed with AN, 1 patient accepted stereotactic radiation therapy, and the remaining 5 patients were on a “wait and scan” strategy.ConclusionThe hearing loss of patients with AN presented with SSNHL may improve with drug treatment. Hearing recovery for SSNHL does not exclude the presence of AN, and all patients initially diagnosed with SSNHL should undergo MRI and ABR to prevent misdiagnosis and delays in potential treatment.

In the clinical intensive care units (ICU), the traditional Chinese medicine (TCM) formulation of Xuebijing has been frequently used for treating sepsis. Nevertheless, the underlying pharmacological mechanisms of Xuebijing remain largely unclear. Caenorhabditis elegans is an important experimental host for bacterial infections. Using C. elegans as an animal model, we here examined the potential of Xuebijing treatment against bacterial infection and the underlying mechanisms. Xuebijing treatment could inhibit the reduction tendency of lifespan caused by Pseudomonas aeruginosa infection. For the cellular mechanisms of this antibacterial infection property, we found that Xuebijing treatment rescued C. elegans lifespan to be against P. aeruginosa infection by inhibiting Pseudomonas colonization in the intestinal lumen. Meanwhile, the increase in the expression of antimicrobial genes induced by Pseudomonas infection was also suppressed by Xuebijing treatment. Moreover, the beneficial effect of Xuebijing against Pseudomonas infection depended on insulin, p38 MAPK, Wnt, DBL-1/TGF-β, ELT-2, and programmed cell death (PCD)-related signals. Although Xuebijing did not show obvious antibacterial activity, Xuebijing (100%) treatment could inhibit the Pseudomonas biofilm formation and decrease the expression of virulence genes (lasA, lasB, rhlA, rhlC, phzA, phzM, phzH, and phzS) and quorum sensing (QS)-related genes (lasI, lasR, rhlI, rhlR, pqsA, and pqsR). Our results support the potential role of Xuebijing treatment against bacterial infection in hosts.

Abstract Background ALAS2 (delta-aminolevulinate synthase 2) is one of the two isoenzymes catalyzing the synthesis of delta-aminolevulinic acid (ALA), which is the first precursor of heme synthesis. ALAS2-overexpressing transgenic mice (Tg mice) showed syndrome of porphyria, a series of diseases related to the heme anabolism deficiency. Tg mice showed an obvious decrease in muscle size. Muscle atrophy results from a decrease in protein synthesis and an increase in protein degradation, which ultimately leads to a decrease in myofiber size due to loss of contractile proteins, organelles, nuclei, and cytoplasm. Methods The forelimb muscle grip strength of age-matched ALAS-2 transgenic mice (Tg mice) and wild-type mice (WT mice) were measured with an automated grip strength meter. The activities of serum LDH and CK-MB were measured by Modular DPP. The histology of skeletal muscle (quadriceps femoris and gastrocnemius) was observed by hematoxylin and eosin (HE) staining, immunohistochemistry, and transmission electron microscope. Real-time PCR was used to detect mtDNA content and UCP3 mRNA expression. Evans blue dye staining was used to detect the membrane damage of the muscle fiber. Single skeletal muscle fiber diameter was measured by single-fiber analyses. Muscle adenosine triphosphate (ATP) levels were detected by a luminometric assay with an ATP assay kit. Results Compared with WT mice, the strength of forelimb muscle and mass of gastrocnemius were decreased in Tg mice. The activities of serum CK-MB and LDH, the number of central nuclei fibers, and Evans blue positive fibers were more than those in WT mice, while the diameter of single fibers was smaller, which were associated with suppressed expression levels of MHC, myoD1, dystrophin, atrogin1, and MuRF1. Re-expression of eMyHC was only showed in the quadriceps of Tg mice, but not in WT mice. Muscle mitochondria in Tg mice showed dysfunction with descented ATP production and mtDNA content, downregulated UCP3 mRNA expression, and swelling of mitochondria. Conclusion ALAS2 overexpressing-transgenic mice (Tg mice) showed muscle dystrophy, which was associated with decreased atrogin-1 and MuRF-1, and closely related to mitochondrial dysfunction.

The major pathological feature of Alzheimer’s disease (AD) is the aggregation of amyloid β peptide (Aβ) in the brain. Inhibition of Aβ42 aggregation may prevent the advancement of AD. This study employed molecular dynamics, molecular docking, electron microscopy, circular dichroism, staining of aggregated Aβ with ThT, cell viability, and flow cytometry for the detection of reactive oxygen species (ROS) and apoptosis. Aβ42 polymerizes into fibrils due to hydrophobic interactions to minimize free energy, adopting a β-strand structure and forming three hydrophobic areas. Eight dipeptides were screened by molecular docking from a structural database of 20 L-α-amino acids, and the docking was validated by molecular dynamics (MD) analysis of binding stability and interaction potential energy. Among the dipeptides, arginine dipeptide (RR) inhibited Aβ42 aggregation the most. The ThT assay and EM revealed that RR reduced Aβ42 aggregation, whereas the circular dichroism spectroscopy analysis showed a 62.8% decrease in β-sheet conformation and a 39.3% increase in random coiling of Aβ42 in the presence of RR. RR also significantly reduced the toxicity of Aβ42 secreted by SH-SY5Y cells, including cell death, ROS production, and apoptosis. The formation of three hydrophobic regions and polymerization of Aβ42 reduced the Gibbs free energy, and RR was the most effective dipeptide at interfering with polymerization.

In the economically developed Beijing–Tianjin–Hebei region, magnetotelluric data are susceptible to contamination from cultural noise, which can be caused, for example, by urban stray currents, high-speed railways, or high-voltage lines. The multiple remote references method is an effective tool that can be used to suppress interference and improve signal-to-noise ratios. Therefore, this paper first introduces the basic principles of multiple remote references and then takes high-speed railway noise as an example. The characteristics of the time domain and frequency domain of the high-speed railway noise signals are analyzed. Then, we use two remote reference stations (with a single remote reference and multiple remote references) to process the data interfering with the high-speed railway and compare the results. Finally, the multiple remote references method is used to process the data for the entire section. Coupled with the known geological and seismic data, the inversion results well-reflect the deep underground geological structure.

Photonics-assisted frequency conversion based on cascaded modulators is an effective way to satisfy the requirements of distributed antenna array applications. A filter-free photonic image-rejection down-converter with immunity to dispersion-induced power fading is proposed and demonstrated. The radio frequency (RF) signal from the distributed antenna unit is injected into a dual-drive Mach–Zehnder modulator (DDMZM) through an electrical 90° hybrid coupler (HC), and a single-sideband (SSB) signal is realized. It is then transmitted to the center office by an optical fiber link. At the center office, the modulated RF signal is injected into a dual-polarization dual-parallel MZM (DP-DPMZM) after a polarization controller (PC). Afterwards, an LO signal remodulates it through the Y-DPMZM, and carrier-suppressed SSB modulation is fulfilled via another electrical 90° HC. After the power splitting, quadrature I and Q IF signals can be obtained by a photonics-based continuously adjustable phase shifter. Through a combination of the I/Q IF signals with a low-frequency electrical 90° HC, a photonics image-rejection down-converter based on phase cancellation is realized. Moreover, no optical filter is required; thus, the image-rejection down-converter can work with a large bandwidth. The proposed filter-free photonic image-rejection down-converter is theoretically analyzed and experimentally verified.

Abstract Long non-coding RNAs (lncRNAs) are important in regulating the response to environmental stresses in organisms. In this study, we used Caenorhabditis elegans as an animal model to determine the functions of intestinal lncRNAs in regulating response to simulated microgravity stress. Among the intestinal lncRNAs, linc-2, linc-46, linc-61, and linc-78 were increased by simulated microgravity treatment, and linc-13, linc-14, linc-50, and linc-125 were decreased by simulated microgravity treatment. Among these 8 intestinal lncRNAs, RNAi knockdown of linc-2 or linc-61 induced a susceptibility to toxicity of simulated microgravity, whereas RNAi knockdown of linc-13, linc-14, or linc-50 induced a resistance to toxicity of simulated microgravity. In simulated microgravity treated nematodes, linc-50 potentially binds to three transcriptional factors (DAF-16, SKN-1, and HLH-30). RNAi knockdown of daf-16, skn-1, or hlh-30 could suppress resistance of linc-50(RNAi) nematodes to the toxicity of simulated microgravity. Therefore, our results provide an important basis for intestinal lncRNAs, such as the linc-50, in regulating the response to simulated microgravity in nematodes.

Background: Sudden sensorineural hearing loss (SSHL) refers to the sudden occurrence of unexplained sensorineural hearing loss. The present study showed that different systemic diseases had different influence on the occurrence and hearing outcome of SSHL. Thyroid hormone is one of the important factors for the development of fetal ear and auditory function. However, the distribution of thyroid dysfunction in SSHL patients and the effect of thyroid dysfunction on the occurrence and hearing outcome of SSHL has not been studied. Methods: In this study, a retrospective analysis had been done in 676 patients with SSHL. We had described the distribution of thyroid function in patients with SSHL in detail, and by the statistical method, analyzed the relationship between the hearing outcome and thyroid dysfunction, respectively. Results: In all patients, 24.41% (165/676) had abnormal thyroid function testing results. The onset age of SSHL in FT3 abnormal group (including low and high group) was younger than that in normal FT3 group. Recovery group had more patients with lower-than-normal T3 level as compared to non-recovery patients. Significant associations between T3 levels and hearing outcome were observed in the subgroup with longer time elapse between symptom onset and treatment (≥14 d). Conclusion: The incidence of thyroid dysfunction in SSHL is significantly higher than in the general population. There was obvious relationship between T3 and FT3 item of thyroid dysfunction and the onset time and hearing outcome of SSHL, which indicated that T3 or FT3 indicator may be one of the affecting factors for the SSHL. Early screening and diagnosis of thyroid dysfunction, especial T3 level, may help to evaluate the prognosis in SSHL patients.