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Background: Neurodevelopmental disorders (NDDs) are a group of diseases that severely affect the physical and mental health of children. The PPP2R5D gene encodes B56δ, the regulatory subunit of protein phosphatase 2A (PP2A). NDDs related to the PPP2R5D gene have recently been defined as Houge–Janssens syndrome 1. Methods: Clinical/whole exome sequencing was performed on approximately 3000 patients with NDDs from 2017 to 2023. In vitro experiments were performed to assess the impairment of variants to protein expression and the assembly of PP2A holoenzyme. The genetic information and phenotypes of the reported patients, as well as patients in this study, were summarized, and the genotype–phenotype relationship was analyzed. The probability of pathogenic missense variants in PPP2R5D was predicted using AlphaMissense (AM), and the relationship between certain phenotype and 3D protein structural features were analyzed. Results: Thirteen new patients carrying twelve PPP2R5D gene variants were detected, including five novel missense variants and one novel frameshift variant. In vitro experiments revealed that the frameshift variant p.H463Mfs*3 resulted in a ~50 kDa truncated protein with lower expression level. Except for E420K and T536R, other missense variants impaired holoenzyme assembly. Furthermore, we found that pathogenic/likely pathogenic (P/LP) variants that have been reported so far were all missense variants and clustered in three conserved regions, and the likelihood of P/LP mutations located in these conserved regions was extremely high. In addition, the macrocephaly phenotype was related to negatively charged residues involved in substrate recruitment. Conclusions: We reported thirteen new patients with PPP2R5D gene variants and expanded the PPP2R5D variant spectrum. We confirmed the pathogenicity of novel variants through in vitro experiments. Our findings in genotype–phenotype relationship provide inspiration for genetic counseling and interpretation of variants. We also provide directions for further research on the mechanism of macrocephaly phenotype.

The papaya mealybug, Paracoccus marginatus, is an invasive pest species found all over the world. It is native to Mexico and Central America, but is now present in more than 50 countries and regions, seriously threatening the economic viability of the agricultural and forestry industry. In the current study, the global potential distribution of P. marginatus was predicted under current and future climatic conditions using MaxEnt. The results of the model assessment indicated that the area under the curve of the receiver operating characteristic ( ROC-AUC) was 0.949, while the TSS value was 0.820. The results also showed that the three variables with the greatest impact on the model were min temperature of coldest month (bio6), precipitation of wettest month (bio13), and precipitation of coldest quarter (bio19), with corresponding contributions of 46.8%, 31.1%, and 13.1%, respectively. The results indicated that the highly suitable areas were mainly located in tropical and subtropical regions, including South America, southern North America, Central America, Central Africa, Australia, the Indian subcontinent, and Southeast Asia. Under four climate scenarios in the 2050s and 2070s, the area of suitability will change very little. Moreover, the results showed that the area of suitable areas in 2070s increased under all four climate scenarios compared to the current climate. In contrast, the area of suitable habitat increases from the current to the 2050s under the SSP370 and SSP585 climate scenarios. The current study could provide a reference framework for the future control and management of papaya mealybug and other invasive species.

This study aimed to examine the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and other clinicopathological features in HER2+ MBC patients who received first-line anti-HER2 therapy. A total of 129 patients were assigned to NLR-low and NLR-high groups based on a cutoff value of 3.0 at baseline. Peripheral blood lymphocyte subsets and gene mutations in circulating tumor DNA were analyzed by flow cytometry and Next-generation sequencing, respectively. Survival was evaluated by the Kaplan–Meier method and Cox regression analysis. Of the 129 patients, 77 and 52 were assigned to the NLR-low (≤3) and NLR-high (>3) groups, respectively. Compared with NLR-high patients, the NLR-low patients had significantly longer median progression-free survival (PFS) (11.7 vs. 7.7 months) (p = 0.001, HR = 2.703 95% CI 1.543–4.736 and overall survival (OS) (37.4 vs. 28.7 months) (p = 0.044, HR = 2.254 95% CI 1.024–4.924). Furthermore, this association was independent of metastatic sites or estrogen receptor status. Peripheral blood CD3+ (p = 0.034) and CD4+ (p = 0.010) T cell numbers were significantly higher in the NLR-low group than the NLR-high group. The mutational profile of MBC was generally similar between the two groups. Baseline NLR was a prognostic factor of PFS and OS for patients with HER2+ MBC in the first-line setting. These results may facilitate the selection of patients who will benefit most from anti-HER2 treatment.

Within the realm of aging, the nexus between diet and health has garnered considerable attention. However, only select studies have amalgamated insights into the correlation between plant and animal food consumption and frailty. Our aim was to appraise the connections between the overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) and frailty in the elderly, utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). This cohort study drew upon CLHLS data spanning from 2008 to 2018. The PDI, hPDI, and uPDI were gauged using a simplified food frequency questionnaire (FFQ). A frailty index, encompassing 35 variables across major health domains, was formulated. Cox proportional hazard models were employed to scrutinize the associations between the three plant-based dietary indices and frailty in older adults, including an exploration of gender disparities in these associations. A cohort of 2883 study participants was encompassed, with 1987 (68.9%) observed to be either frail or in the pre-frail stage. The Cox model with penalized spline exhibited linear associations of PDI, hPDI, and uPDI with the frailty index. Following covariate adjustments, it was discerned that older adults situated in the highest quartiles of PDI (HR = 0.86, 95% CI: 0.77–0.95) and hPDI (HR = 0.83, 95% CI: 0.74–0.93) experienced a 14% and 17% diminished risk of frailty compared to those in the lowest quartiles of PDI and hPDI, respectively. Conversely, when contrasted with those in the lowest quartile of uPDI, older adults adhering to the highest tertile of uPDI exhibited a 21% elevated risk of frailty (HR = 1.21, 95% CI: 1.08–1.36), with both associations achieving statistical significance (p < 0.01). Moreover, additional subgroup analyses revealed that the protective effects of PDI and hPDI against frailty and the deleterious effects of uPDI were more conspicuous in men compared to women. To forestall or decelerate the progression of frailty in the elderly, tailored dietary interventions are imperative, particularly targeting male seniors.

Branched hydraulic lines are prone to leakage and break under complex working conditions. The coupling vibration problem caused by the fluid pressure beat and external mechanical excitation of the pump at the junction of the branch of the cross-type hydraulic pipeline is very common. So a method combining finite element simulation and fluid-structure interaction vibration experiments is proposed for research. First, the possibility of the finite element method in solving the pipeline vibration problem is verified, and then the modal analysis and harmonious response analysis of the cross-type pipe are carried out to discuss the influence of fluid pressure and solid elastic modulus on pipeline vibration. The results show that as the fluid pressure and pipeline elastic modulus change, different modes of different orders will be affected. Under external excitation, only a portion of the order is sensitive to external excitation.

Pseudaucalaspis pentagona and P. prunicola are notorious pests and commonly feed on various ornamental plants and fruit trees worldwide. The two species share many host-plant species, and are similar in morphological characteristics and life cycle, making it difficult to distinguish to distinguish between them. In this study, morphological characteristics, molecular evidence, and ecological niches were used to define these species. We performed PCA analysis on 22 morphological characteristics that allowed the delineation of the species. We then sequenced the COI gene of both species revealing five populations of P. pentagona and one population of P. prunicola, and the higher support rate could distinguish the two species. We also identified the potential distribution area of the two species based on the MaxEnt niche model, which showed that the degree of niche overlap was high, but that they occupied different niches. Ultimately, we combined three lines of evidence to show that the two species are distinctly different. This study supports species definition using combined morphology, genetics, and ecology and provides a theoretical basis for the effective control of these two pests in the future.

As a new type of one-dimensional semiconductor nanometer material, silicon nanowires (SiNWs) possess good application prospects in the field of biomedical sensing. SiNWs have excellent electronic properties for improving the detection sensitivity of biosensors. The combination of SiNWs and field effect transistors (FETs) formed one special biosensor with high sensitivity and target selectivity in real-time and label-free. Recently, SiNW-FETs have received more attention in fields of biomedical detection. Here, we give a critical review of the progress of SiNW-FETs, in particular, about the reversible surface modification methods. Moreover, we summarized the applications of SiNW-FETs in DNA, protein, and microbial detection. We also discuss the related working principle and technical approaches. Our review provides an extensive discussion for studying the challenges in the future development of SiNW-FETs.

Traffic incidents pose substantial hazards to public safety and wellbeing, and accurately estimating their duration is pivotal for efficient resource allocation, emergency response, and traffic management. However, existing research often faces limitations in terms of limited datasets, and struggles to achieve satisfactory results in both prediction accuracy and interpretability. This paper established a novel prediction model of traffic incident duration by utilizing a tabular network-TabNet model, while also investigating its interpretability. The study incorporates various novel aspects. It encompasses an extensive temporal and spatial scope by incorporating six years of traffic safety big data from Tianjin, China. The TabNet model aligns well with the tabular incident data, and exhibits a robust predictive performance. The model achieves a mean absolute error (MAE) of 17.04 min and root mean squared error (RMSE) of 22.01 min, which outperforms other alternative models. Furthermore, by leveraging the interpretability of TabNet, the paper ranks the key factors that significantly influence incident duration and conducts further analysis. The findings emphasize that road type, casualties, weather conditions (particularly overcast), and the number of motor and non-motor vehicles are the most influential factors. The result provides valuable insights for traffic authorities, thus improving the efficiency and effectiveness of traffic management strategies.

Continuous cropping increases disease severity and causes arrested development of chilli plants and the decrease of yield and quality. Hemp-chilli rotation cropping evidently eased chilli diseases, but the causation remains unknown. This paper investigated the disease index (DI) of chilli’s anthracnose for hemp-chilli and continuous chilli cropping, the antifungal effect of water extract of hemp and chilli residues, and bacteria antagonistic to chilli anthracnose fungus from hemp and chilli rhizosphere. Hemp grown as a preceding crop decreased anthracnose DI from 35–39% for the continuous chilli to 14–15% for hemp-chilli rotation. Hemp residue water extract executed suppression of chilli anthracnose fungus and the efficiency increased as the extract concentration increased from 1% to 5%. Hemp extract concentration 5% gave a mean inhibition ratio (IR) of 32.34% to spore germination and IR 53.72% to mycelia growth, which was much greater than that of the chilli extract. Antagonistic bacteria isolated from the hemp rhizosphere evidently depressed the mycelia growth of the fungus with a mean IR 32.35%, while no antagonistic bacteria were obtained from the chilli rhizosphere. The stronger allelopathy of preceding hemp plants and antagonistic bacteria from the hemp rhizosphere synergistically suppressed the fungus growth and eased the disease in the succeeding chilli crop.

Cyclic diguanylate (c-di-GMP) affects bacterial physiological and biochemical functions like biofilm, motility, virulence, and bacterial secretion systems. GGDEF/EAL-domain proteins, participating in c-di-GMP synthesis and degradation, are widely present in Pseudomonas, with various structures and functions. Pseudomonas glycinae MS82 is a rhizosphere bacterium that protects mushroom against the pathogenic fungi. Although 14 genes encoding GGDEF/EAL-domain proteins have been identified in the genome of MS82, c-di-GMP regulation is poorly understood as a facilitator or repressor of physiological phenotypes. Here, PafQ and PafR, encoding the proteins with the tandem GGDEF/EAL domain, were functionally analyzed and found to regulate antifungal activity. Individual deletion mutants of PafQ and PafR were constructed in P. glycinae MS82 through biparental conjugation and homologous recombination. Subsequently, antifungal activity, biofilm formation, motility, and expression of the genes related to antifungal substance synthesis were examined and contrasted with those of wild-type P. glycinae MS82. Most phenotypes of physiological activities were significantly reduced after knocking out PafQ or PafR. In other members of the genus Pseudomonas, homologous genes of PafQ and PafR possess different functions in c-di-GMP regulation. In P. glycinae, the positive regulation of PafQ and PafR on fungistatic substance synthesis, biofilm formation, and motility is crucial in the biocontrol of mushroom diseases.

Hyper-reactivity to sensory inputs is a common and debilitating symptom of autism spectrum disorder (ASD), but the underlying neural abnormalities remain unclear. Two of three patients in our clinical cohort screen harboring de novo SHANK2 mutations also exhibited high sensitivity to visual, auditory, and tactile stimuli, so we examined whether shank2 deficiencies contribute to sensory abnormalities and other ASD-like phenotypes by generating a stable shank2b-deficient zebrafish model (shank2b−/−). The adult shank2b−/− zebrafish demonstrated reduced social preference and kin preference as well as enhanced behavioral stereotypy, while larvae exhibited hyper-sensitivity to auditory noise and abnormal hyperactivity during dark-to-light transitions. This model thus recapitulated the core developmental and behavioral phenotypes of many previous genetic ASD models. Expression levels of γ-aminobutyric acid (GABA) receptor subunit mRNAs and proteins were also reduced in shank2b−/− zebrafish, and these animals exhibited greater sensitivity to drug-induced seizures. Our results suggest that GABAergic dysfunction is a major contributor to the sensory hyper-reactivity in ASD, and they underscore the need for interventions that target sensory-processing disruptions during early neural development to prevent disease progression.

Connectivity in large-scale data center networks is a critical indicator to evaluate network state. A feasible and performance-guaranteed algorithm enables us to find disjoint paths between network vertices to ensure effective data transfer and to maintain the normal operation of network in case of faulty nodes. As an important data center network, BCube Connected Crossbars (BCCC) has many excellent properties that have been widely studied. In this paper, we first propose a vertex disjoint path algorithm with the time complexity of O(nk) in BCCC, where n denotes a switch connected to n servers and k denotes dimension. Then, we prove that the restricted connectivity of BCCC(n,k). Finally, we present an O(knκ1(G)) fault-free algorithm in BCCC, where κ1(G) is the restricted connectivity. This algorithm can obtain a fault-free path between any two distinct fault-free vertices under the condition that each vertex has at least one fault-free neighbor in the BCCC and a set of faulty vertices F with |F|<κ1(G).

Sponge city is a method of managing rain floods, proposed by China to deal with urban waterlogging and the overflow pollution of drainage pipe networks, which indicates a more effective strategy to promote urban sustainable development. Due to the diversity of sponge city construction objectives and the complexity of the developmental system, a unified and effective sustainability evaluation method has not yet been formed. Based on the emergy analysis method, the indicators of ecosystem service, the construction cost, the runoff regulation, and the pollutant reduction of sponge city construction are thus included in the evaluation system, and the sustainable evaluation model of a sponge city is fully constructed. Taking the core area in the south of Haicang in Xiamen City as the studying object, the runoff regulation, and the pollutant reduction indicators, are carefully obtained by using Info Works simulation software. The results showed that: ① the quality of COD (Chemical Oxygen Demand) of pollutants discharged from the research object is 409.8t/a, the total runoff is 3.579 million m3/a, the current annual total runoff control rate is 37.15%, and the current emergy index ESI of sponge city system is 0.05 < 1, which is in an unsustainable state, It is necessary to upgrade and transform the urban underlying surface; ② The transformation intensity of three LID (Low Impact Development) facilities, i.e., concave green space, permeable pavement and green roof, is carefully selected as different construction schemes. When the construction intensity of LID is 25%, the emergy index ESI (Emergy Sustainable Index) = 1.08, which meets the basic requirements of sustainable development; As long as the reconstruction construction intensity is 30%, the growth value of ESI, ΔESI, is the largest, the sustainable growth effect of sponge city construction is the most obvious, and the marginal benefit is the largest; ③ As long as the total annual runoff control rate of the research object is 69–82%, its sustainable energy index ESI should be within the range of 1.39–1.83. If ESI is less than 1.39, this indicates that the total annual runoff control rate of the research area cannot adapt to the planning requirements of 69%.

Cyclic dimeric guanosine monophosphate (c-di-GMP) is synthesized by diguanylate cyclase (DGC) with the GGDEF domain. As a ubiquitous bacterial second messenger, it regulates diverse life-activity phenotypes in some bacteria. Although 38 genes encoding GGDEF-domain-containing proteins have been identified in the genome of the Pseudomonas glycinae strain MS82, whether c-di-GMP functions as a facilitator or repressor of life-activity phenotypes is poorly understood. In this study, one of the 38 genes containing a GGDEF domain in MS82, PafS was investigated to explore its regulatory function in bacterial life activities. The PafS-deletion mutant ΔPafS and reversion mutant PafS-comp were constructed by the method of biparental conjugation and homologous recombination. The life activities of the mutants, such as antifungal activity, biofilm formation ability, polysaccharide content, and motor behavior, were explored. The results showed that all life-activity phenotypes were significantly reduced after knocking out PafS, whereas all were significantly restored to a similar level to that of MS82 after the complementation of PafS. These results suggested that PafS plays an important role in the regulation of a range of cellular activities by c-di-GMP in P. glycinae MS82.

Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder in which genetics play a major role. Molecular diagnosis may lead to a more accurate prognosis, improved clinical management, and potential treatment of the condition. Both copy number variations (CNVs) and single nucleotide variations (SNVs) have been reported to contribute to the genetic etiology of ASD. The effectiveness and validity of clinical targeted panel sequencing (CTPS) designed to analyze both CNVs and SNVs can be evaluated in different ASD cohorts. CTPS was performed on 573 patients with the diagnosis of ASD. Medical records of positive CTPS cases were further reviewed and analyzed. Additional medical examinations were performed for a group of selective cases. Positive molecular findings were confirmed by orthogonal methods. The overall positive rate was 19.16% (109/569) in our cohort. About 13.89% (79/569) and 4.40% (25/569) of cases had SNVs only and CNVs only findings, respectively, while 0.9% (5/569) of cases had both SNV and CNV findings. For cases with SNVs findings, the SHANK3 gene has the greatest number of reportable variants, followed by gene MYT1L. Patients with MYT1L variants share common and specific clinical characteristics. We found a child with compound heterozygous SLC26A4 variants had an enlarged vestibular aqueduct syndrome and autistic phenotype. Our results showed that CTPS is an effective molecular diagnostic tool for ASD. Thorough clinical and genetic evaluation of ASD can lead to more accurate diagnosis and better management of the condition.

Nanofiltration (NF) is a promising post-treatment technology for providing high-quality drinking water. However, membrane fouling remains a challenge to long-term NF in providing high-quality drinking water. Herein, we found that coupling pre-treatments (sand filtration (SF) and ozone–biological activated carbon (O3-BAC)) and NF is a potent tactic against membrane fouling while achieving high-quality drinking water. The pilot results showed that using SF+O3-BAC pre-treated water as the feed water resulted in a lower but a slowly rising transmembrane pressure (TMP) in NF post-treatment, whereas an opposite observation was found when using SF pre-treated water as the feed water. High-performance size-exclusion chromatography (HPSEC) and three-dimensional excitation–emission matrix (3D-EEM) fluorescence spectroscopy determined that the O3-BAC process changed the characteristic of dissolved organic matter (DOM), probably by removing the DOM of lower apparent molecular weight (LMW) and decreasing the biodegradability of water. Moreover, amino acids and tyrosine-like substances which were significantly related to medium and small molecule organics were found as the key foulants to membrane fouling. In addition, the accumulation of powdered activated carbon in O3-BAC pre-treated water on the membrane surface could be the key reason protecting the NF membrane from fouling.

Transgenic silkworm expression systems have been applied for producing various recombinant proteins. Knocking out or downregulating an endogenous silk protein is considered a viable strategy for improving the ability of transgenic expression systems to produce exogenous proteins. Here, we report the expression of human epidermal growth factor (hEGF) in a P25 gene knockout silkworm. The hEGF gene regulated by the P25 gene promoter was integrated into a silkworm’s genome. Five transgenic positive silkworm lineages were generated with different insertion sites on silkworm chromosomes and the ability to synthesize and secrete proteins into cocoons. Then, a cross-strategy was used to produce transgenic silkworms with a P25 gene knockout background. The results of the protein analysis showed that the loss of an endogenous P25 protein can increase the hEGF production to about 2.2-fold more than normal silkworms. Compared to those of transgenic silkworms with wild type (non-knockout) background, the morphology and secondary structure of cocoon silks were barely changed in transgenic silkworms with a P25 gene knockout background, indicating their similar physical properties of cocoon silks. In conclusion, P25 gene knockout silkworms may become an efficient bioreactor for the production of exogenous proteins and a promising tool for producing various protein-containing silk biomaterials.

Finding an appropriate shape for the releasing building is thoroughly relevant given the energy dissipation and safety requirements of a high dam in a sediment-laden river. Thirty-six physical experiments on trajectory energy dissipation were conducted, researching the influence of three overflow shapes (contraction ratios of 0.5, 0.4, and 0.3) with four sediment concentrations (0, 50, 150, and 250 kg/m3) on the discharge, flow regime, and hydrodynamic pressure of a plunge pool slab. The experimental results demonstrated that the flow coefficient gradually decreased as the contraction ratio decreased in a relatively high weir head, regardless of the sediment concentration. The water nappe narrowed and the length of the longitudinal trajectory increased as the outlet shrinkage and sediment concentration decreased. With the increase in sediment concentration, the nappe regime approached stability, and the flow in the plunge pool tended toward small rolling, causing the impact pressure and fluctuating pressure to increase. Changes in overflow shape had little effect on the position of pressure peak, but the value became lower as the ratio diminished. The influence on the hydrodynamic pressure by outlet shrinkage became attenuated while the sediment concentration increased. The fluctuating energy and vortex scale were enhanced due to the increased viscosity with increasing sediment concentrations.

The effect of sediment on the hydraulics of jet energy dissipation is an urgent issue for high dams built on sediment-laden rivers. Accordingly, flume experiments were conducted using a ski-jump type energy dissipator in flows of four sediment concentrations (0 kg/m3, 50 kg/m3, 150 kg/m3, and 250 kg/m3) to determine the effects on discharge, flow regime, and hydrodynamic pressure in a plunge pool. The results demonstrate that the effect of sediment on discharge is constant, regardless of sediment concentration, when compared to fresh water. The width of the nappe decreased with increasing concentrations of sediment. The length of the jet trajectory increased with upstream water head. The time-averaged pressure and fluctuation pressure both exhibited peaks, describing the impact of the jet on the bottom of the plunge pool. The maximum time-averaged pressure and maximum fluctuating pressure both noticeably increased with upstream water head and slightly increased with sediment concentration for a given flow condition. The results also demonstrated that the dominant frequency of fluctuation trends to lower values, and that both the fluctuating energy and vortex scale increase with increasing sediment concentrations due to increased viscosity. These findings can be used to improve energy dissipation in dams on sediment-laden rivers.

A series of Lewis acidic metal salts were used for glucose dehydration to 5-hydroymethylfurfural (HMF) in water. Effect of valence state, ionic radii of Lewis acidic cation, and the type of anions on the catalytic performance have been studied systematically. The experimental results showed that the valence state played an important role in determining catalytic activity and selectivity. It was found that a higher glucose conversion rate and HMF selectivity could be obtained over high valent Lewis acid salts, where the ionic radii of these Lewis acidic metal salts are usually relatively small. Analysis on the effect of the anions of Lewis acid salts on the catalytic activity and the selectivity suggested that a higher glucose conversion and HMF selectivity could be readily obtained with Cl−. Furthermore, the recyclability of high valence state Lewis acid salt was also studied, however, inferior catalytic performance was observed. The deactivation mechanism was speculated to be the fact that high valence state Lewis acid salt was comparatively easier to undergo hydrolysis to yield complicated metal aqua ions with less catalytic activity. The Lewis acidic activity could be recovered by introducing a stoichiometric amount of hydrochloric acid (HCl) to the catalytic before the reaction.

The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical Candida isolates (including 400 C. albicans, 200 C. glabrata, 200 C. parapsilosis, 150 C. tropicalis and 50 C. krusei) and 150 Aspergillus isolates (100 A. fumigatus and 50 A. flavus) from the Eastern China Invasive Fungi Infection Group (ECIFIG) was tested for the antifungals including anidulafungin, rezafungin, caspofungin and fluconazole. The echinocandins showed strong activity against C. albicans that was maintained against fluconazole-resistant isolates. The GM MIC (geometric mean minimum inhibitory concentration) value of rezafungin was found to be comparable to that of anidulafungin or caspofungin against the five tested common Candida species. C. tropicalis exhibited higher resistance rates (about 8.67–40.67% in different antifungals) than the other four Candida species. Through the sequencing of FKS genes, we searched for mutations in echinocandin-resistant C. tropicalis isolates and found that all displayed alterations in FKS1 S654P. The determined MEC (minimal effective concentration) values against A. fumigatus and A. flavus for rezafungin (0.116 μg/mL, 0.110 μg/mL) are comparable to those of caspofungin (0.122 μg/mL, 0.142 μg/mL) but higher than for anidulafungin (0.064 μg/mL, 0.059 μg/mL). Thus, the in vitro activity of rezafungin appears comparable to anidulafungin and caspofungin against most common Candida and Aspergillus species. Rezafungin showed higher susceptibility rates against C. glabrata. Rezafungin indicates its potent activity for potential clinical application.

High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms underlying cancer progression. Aneuploidy and copy number variation (CNV) partially contribute to the heightened malignancy observed in EOC; however, the precise features of aneuploidy and their underlying molecular patterns, as well as the relationship between CNV and aneuploidy in EOC, remain unclear. In this study, we employed single-cell sequencing data along with The Cancer Genome Atlas (TCGA) to investigate aneuploidy and CNV in EOC. The technique of fluorescence in situ hybridization (FISH) was employed using specific probes. The copy number variation within the genomic region of chromosome 8 (42754568-47889815) was assessed and utilized as a representative measure for the ploidy status of individual cells in chromosome 8. Differential expression analysis was performed between different subgroups based on chromosome 8 ploidy. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), and hub–gene analyses were subsequently utilized to identify crucial genes involved. By classifying enriched tumor cells into distinct subtypes based on chromosome 8 ploidy combined with TCGA data integration, we identified key genes driving chromosome 8 aneuploidy in EOC, revealing that PRKDC gene involvement through the mediated non-homologous end-joining pathway may play a pivotal role in disease progression. Further validation through analysis of the GEO and TCGA database and survival assessment, considering both mRNA expression levels and CNV status of PRKDC, has confirmed its involvement in the progression of EOC. Further functional analysis revealed an upregulation of PRKDC in both ovarian EOC cells and tissues, with its expression showing a significant correlation with the extent of copy number variation (CNV) on chromosome 8. Taken together, CNV amplification and aneuploidy of chromosome 8 are important characteristics of EOC. PRKDC and the mediated NHEJ pathway may play a crucial role in driving aneuploidy on chromosome 8 during the progression of EOC.

Food-derived peptides have been extensively studied for their benefits in humans. Hen eggs, characterized by high protein and digestibility, are an excellent source of food-derived bioactive peptides. This review summarizes the preparation methods, purification, and identification of hen egg-derived peptides (HEPs). The preparation methods mainly include enzymatic hydrolysis, microbial fermentation, and chemical synthesis. Genetic engineering is an emerging trend of HEP preparation. Then, we summarize the biological activities of HEPs, such as antioxidant activities, enzyme inhibitory activity, and antibacterial activity, of which the enzyme inhibitory activity is comprehensively summarized for the first time. The structure–activity relationship and underlying mechanism of the HEPs are further elucidated. Finally, the applications, future challenges, and opportunities of HEPs were mainly discussed in the food and non-food sectors. We focus on the potential applications of HEPs in intestinal health and assembly delivery and provide a reference for the further utilization and commercial development of HEPs.

The fall armyworm, Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), a common agricultural pest known for its extensive migration and wide host ranges, causes considerable harm to maize (Zea mays L.). In this study, we utilized two molecular marker genes, COI and Tpi, to compare the genetic characteristics of the collected original samples. Additionally, through an interactive study between S. frugiperda larvae and six maize varieties aiming to understand the insect’s adaptability and resistance mechanisms, our analysis revealed that both the COI and Tpi genes identified S. frugiperda as the corn strain. Further examination of the larvae showed significant differences in nutritional indices, digestive, and detoxification enzyme activities. Special maize varieties were found to offer higher efficiency in nutrient conversion and assimilation compared with common varieties. This study revealed adaptations in S. frugiperda’s digestive and detoxification processes in response to the different maize varieties. For instance, larvae reared on common maize exhibited elevated amylase and lipase activities. Interestingly, detoxification enzyme activities exhibited different patterns of variation in different maize varieties. The Pearson correlation analysis between nutritional indices, enzyme activities, and the nutritional content and secondary metabolites of maize leaves provided deeper insights into the pest’s adaptability. The results highlighted significant relationships between specific nutritional components in maize and the physiological responses of S. frugiperda. Overall, our findings contribute substantially to the understanding of S. frugiperda’s host plant adaptability, offering critical insights for the development of sustainable pest management strategies.

This study aimed to isolate polysaccharides from Penthorum chinense Pursh and evaluate their rheological characteristics, physicochemical properties, and antioxidant activity. The optimal conditions for the maximal extraction yield of Penthorum chinense Pursh polysaccharides (4.05 ± 0.12%) were determined by employing a single-factor test and response surface methodology which included an extraction time of 3 h, a liquid–solid ratio of 20 mL/g, and three separate extraction times. The rheological experiments showcased that the P. chinense polysaccharides exhibited typical shear-thinning behavior, with their apparent viscosity being influenced by various parameters such as concentration, pH, temperature, salt content, and freeze–thaw. The purified polysaccharides (PCP-100), having an average molecular weight of 1.46 × 106 Da, mainly consisted of glucose (18.99%), arabinose (22.87%), galactose (26.72%), and galacturonic acid (21.89%). Furthermore, the PCP-100 exhibited high thermal stability and displayed an irregular sheet-like morphology. Its superior reducing power and free radical scavenging ability implied its significant antioxidant activity in vitro. Collectively, these findings provide important insights for the future application of P. chinense polysaccharides in the food industry.

In plant cells, multiple paralogs from ribosomal protein (RP) families are always synchronously expressed, which is likely contributing to ribosome heterogeneity or functional specialization. However, previous studies have shown that most RP mutants share common phenotypes. Consequently, it is difficult to distinguish whether the phenotypes of the mutants have resulted from the loss of specific genes or a global ribosome deficiency. Here, to investigate the role of a specific RP gene, we employed a gene overexpression strategy. We found that Arabidopsis lines overexpressing RPL16D (L16D-OEs) display short and curled rosette leaves. Microscopic observations reveal that both the cell size and cell arrangement are affected in L16D-OEs. The severity of the defect is positively correlated with RPL16D dosage. By combining transcriptomic and proteomic profiling, we found that overexpressing RPL16D decreases the expression of genes involved in plant growth, but increases the expression of genes involved in immune response. Overall, our results suggest that RPL16D is involved in the balance between plant growth and immune response.

Dandelion (Taraxacum mongolicum Hand.-Mazz.) is a medicinal and edible plant. Dandelion has great development value for its health promoting benefits; additionally, Dandelion grows almost anywhere in the world. In this study, we report the structural characteristics and anti-cancer activity of novel dandelion leaf polysaccharides extracted by pressurized hot water extraction at 120 °C (DLP120) with Mw relative to dextran of 1.64 × 106 Da. Structural analysis indicated that DLP120 is a complex polysaccharide composed of pectin and arabinogalactan. It was mainly composed of arabinose (32.35 mol%) and galactose (44.91 mol%). The main glycosidic linkages of DLP120 were 4-β-D-Galp, 4-α-D-GalpA, T-β-D-Galp, 5-α-L-Araf, 3,5-α-L-Araf, and T-α-L-Araf. In vitro, DLP120 inhibited HepG2 cell proliferation in a dose-dependent manner by inducing cell apoptosis. Cell cycle detection results revealed that DLP120 mainly arrests the cell cycle in S phase. Cells treated with DLP120 displayed obvious apoptotic morphology, including cell volume shrinks and cytoskeleton breaks down. In short, DLP120 has potential as an anti-cancer agent.

Grasspea (Lathyrus sativus L.), a legume crop with excellent resistance to a broad array of environmental stressors, has, to this point, been poorly genetically characterized. High-density genetic linkage maps are critical for draft genome assembly, quantitative trait loci (QTLs) analysis, and gene mining. The lack of a high-density genetic linkage map has limited both genomic studies and selective breeding in grasspea. Here, we developed a high-density genetic linkage map of grasspea using genotyping-by-sequencing (GBS) to sequence 154 grasspea plants, comprising 2 parents and 152 F2 progeny. In all, 307.74 Gb of data was produced, including 2,108,910,938 paired-end reads, as well as 3536 SNPs mapped to seven linkage groups (LG1–LG7). With an average length of 996.52 cM per LG, the overall genetic distance was 6975.68 cM. Both the χ2 test and QTL analysis, based on the Kruskal–Wallis (KW) test and interval mapping (IM) analysis, revealed the monogenic inheritance of flower color in grasspea, with the responsible QTL located between 308.437 cM and 311.346 cM in LG4. The results can aid grasspea genome assembly and accelerate the selective breeding of new grasspea germplasm resources.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited treatment options and high mortality. The oxytocin receptor (OTR) is a class-A G protein-coupled receptor that has been linked to breast cancer, but its role in tumorigenesis and disease progression remains underexplored. OTR expression is highest in tumour-adjacent breast tissue, followed by normal and tumour tissue, indicating a potential role in the tumour microenvironment. OTR levels were higher in migrated MDA-MB-231 cells than in the control parental cells cultured in normal medium; OTR overexpression/knock-down and metastasis biomarker experiments revealed that high OTR expression enhanced metastasis capabilities. These findings align well with data from a murine breast cancer metastasis model, where metastasised tumours had higher OTR expression than the corresponding primary tumours, and high OTR expression also correlates to reduced survival in TNBC patients. OTR agonists/antagonists did not affect MDA-MB-231 cell migration, and pharmacological analysis revealed that the OT/OTR signalling was compromised. High OTR expression enhanced cell migration in an OTR ligand-independent manner, with the underlying mechanism linked to the EGF-mediated ERK1/2-RSK-rpS6 pathway. Taken together, high OTR expression seems to be involved in TNBC metastasis via increasing cell sensitivity to EGF. These results support a potential prognostic biomarker role of OTR and provide new mechanistic insights and opportunities for targeted treatment options for TNBC.

Gastric cancer is considered to be one of the most common causes of cancer death worldwide due to its high recurrence and metastasis rates. The molecule 23,24-Dihydrocucurbitacin E (DHCE) is a cucurbitacin-derived tetracyclic triterpenoid compound that has anti-tumor activity, but the exact mechanism remains to be elucidated. This research aimed to explore the effects of DHCE on human gastric cancer cells and the possible mechanisms. The results showed that DHCE suppressed proliferation, migration, and invasion of gastric cancer cells, as well as induced apoptosis and G2/M phase arrest. Mechanistically, the potential targets and pathways of DHCE were predicted using database screening and verified using a molecular docking study, fluorescence staining, and Western blot. The results indicated that DHCE obviously inhibited the kinase activity of ERK2 via targeting its ATP-binding domain, destroyed F-actin microfilament, and reduced the expression levels of Ras, p-c-Raf, ERK, p-ERK, and MMP9 proteins. Collectively, our study demonstrated that DHCE suppressed gastric cancer cells’ proliferation, migration, and invasion through targeting ERK2 and disrupting the Ras/Raf/ERK/MMP9 signaling pathway. These properties make DHCE a promising candidate drug for the further design and development of novel and effective Ras/Raf/ERK/MMP9 pathway inhibitors for treating gastric cancer.

This study explored the preliminary structural characteristics and in vivo anti-tumor activity of an acidic water-soluble polysaccharide (BCP) separated purified from Bupleurum chinense DC root. The preliminary structural characterization of BCP was established using UV, HPGPC, FT-IR, IC, NMR, SEM, and Congo red. The results showed BCP as an acidic polysaccharide with an average molecular weight of 2.01 × 103 kDa. Furthermore, we showed that BCP consists of rhamnose, arabinose, galactose, glucose, and galacturonic acid (with a molar ratio of 0.063:0.788:0.841:1:0.196) in both α- and β-type configurations. Using the H22 tumor-bearing mouse model, we assessed the anti-tumor activity of BCP in vivo. The results revealed the inhibitory effects of BCP on H22 tumor growth and the protective actions against tissue damage of thymus and spleen in mice. In addition, the JC-1 FITC-AnnexinV/PI staining and cell cycle analysis have collectively shown that BCP is sufficient to induce apoptosis and of H22 hepatocarcinoma cells in a dose-dependent manner. The inhibitory effect of BCP on tumor growth was likely attributable to the S phase arrest. Overall, our study presented significant anti-liver cancer profiles of BCP and its promising therapeutic potential as a safe and effective anti-tumor natural agent.

With the widespread clinical use of drug combinations, the incidence of drug–drug interactions (DDI) has significantly increased, accompanied by a variety of adverse reactions. Drug transporters play an important role in the development of DDI by affecting the elimination process of drugs in vivo, especially in the pathological state. Tubulointerstitial fibrosis (TIF) is an inevitable pathway in the progression of chronic kidney disease (CKD) to end-stage renal disease. Here, the dynamic expression changes of eleven drug transporters in TIF kidney have been systematically investigated. Among them, the mRNA expressions of Oat1, Oat2, Oct1, Oct2, Oatp4C1 and Mate1 were down-regulated, while Oat3, Mrp2, Mrp4, Mdr1-α, Bcrp were up-regulated. Pearson correlation analysis was used to analyze the correlation between transporters and Creatinine (Cr), OCT2 and MATE1 showed a strong negative correlation with Cr. In contrast, Mdr1-α exhibited a strong positive correlation with Cr. In addition, the pharmacokinetics of cimetidine, ganciclovir, and digoxin, which were the classical substrates for OCT2, MATE1 and P-glycoprotein (P-gp), respectively, have been studied. These results reveal that changes in serum creatinine can indicate changes in drug transporters in the kidney, and thus affect the pharmacokinetics of its substrates, providing useful information for clinical use.

Protein stability is largely regulated by post-translational modifications, such as ubiquitination, which is mediated by ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin ligase E3 with substrate specificity. Membrane-associated RING-CH (MARCH) proteins represent one novel family of transmembrane E3 ligases which target glycoproteins for lysosomal destruction. While most of the MARCH family members are known to degrade membrane proteins in immune cells, their tumor-intrinsic role is largely unknown. In this study, we found that the expression of one MARCH family member, MARCH8, is specifically downregulated in breast cancer tissues and positively correlated with breast cancer survival rate according to bioinformatic analysis of The Cancer Genomic Atlas (TCGA) dataset. MARCH8 protein expression was also lower in a variety of human breast cancer cell lines in comparison to immortalized human mammary epithelial MCF-12A cells. Restoration of MARCH8 expression induced apoptosis in human breast cancer cell lines MDA-MB-231 and BT549. Stable expression of MARCH8 inhibited tumorigenesis and lung metastases of MDA-MB-231 cells in mice. Moreover, we discovered that the breast cancer stem-cell marker and metastasis driver CD44, a membrane protein, interacts with MARCH8 and is one of the glycoprotein targets subject to MARCH8-dependent lysosomal degradation. Unexpectedly, we identified a nonmembrane protein, signal transducer and transcription activator 3 (STAT3), as another essential ubiquitination target of MARCH8, whose degradation through the proteasome pathway is responsible for the proapoptotic changes mediated by MARCH8. These findings highlight a novel tumor-suppressing function of MARCH8 in targeting both membrane and nonmembrane protein targets required for the survival and metastasis of breast cancer cells.

Obtaining the water volume of small- and medium-sized lakes in enclosed watersheds with scarce data is a global focus of research. River flow into a lake is an important factor affecting the water volume. However, most river flow measurement methods involve long cycles, low efficiency, and transdisciplinary expertise, making rapid assessments in ungauged basins impossible. This paper proposes a remote sensing flow estimation method based on multi-source remote sensing data, which quickly assesses river flow and provides important input data for lake water volume simulation. The cross-section flow was estimated by extracting the river width. The calculated results were consistent with the measured data, with accuracy greater than 90%. The results compared with daily data measured at hydrological stations, and the Nash coefficient was greater than 0.9. Additionally, the simulation method for lake area, water volume, and water level was constructed using river inflow input data, greatly reducing the parameters required by the conventional lake water volume simulation method. Based on the remote sensing discharge estimation method, we quickly and conveniently obtained changes in river flow into the lake, simulated lake water volume, and provided the basis for water resource management in terminal lake basins with scarce data.

Highly hydrophobic cotton fabrics were obtained with poly(methylhydrogen)siloxane (PMHS) and a further fluorinated olefin modification. The chemical structures and microstructures of PMHS-modified cotton fabrics were characterized, and application of the resultant cotton fabrics in stain resistance and oil–water separation was demonstrated. PMHS chains with very low surface energy were grafted onto cotton fabric by the dehydrogenation reaction between –Si–H of PMHS and –OH groups of cotton fabric at room temperature. The water contact angle of PMHS-modified cotton fabric was 141.7°, which provided the modified cotton fabric with good stain resistance to waterborne pollutants. The separation efficiency of diesel from water was higher than 92% for 20 repeatable separation cycles. A further improvement in stain resistance to oil was also demonstrated by a further addition reaction of 1H,1H,2H-perfluoro-1-decene with PMHS-modified cotton fabric.

This paper presents a new perspective of national power—sustainable national power (SNP)—emphasizing both the traditional comprehensive national power (CNP) and social and environmental sustainability. We propose a measurement to quantify the SNP based on the measurement of comprehensive national power and a sustainable adjusted index. In addition, density-equalizing maps are adopted to visualize the sustainable national power of countries in order to gain a better understanding for its current state and future development from a cartographic perspective. China and its neighboring countries are selected as a case study area. The results show that China outperforms other countries in most of the CNP dimensions but performs poorly in various SNP-adjusted dimensions within the study area. The composite score shows that China is with the highest regional SNP, followed by Japan, Russia, South Korea and India. Furthermore, time series of cartograms reveal evidence showing power transitions among countries. In addition, the effectiveness of cartograms for cartographic communication is discussed.

Ship detection with polarimetric synthetic aperture radar (PolSAR) has received increasing attention for its wide usage in maritime applications. However, extracting discriminative features to implement ship detection is still a challenging problem. In this paper, we propose a novel ship detection method for PolSAR images via task-driven discriminative dictionary learning (TDDDL). An assumption that ship and clutter information are sparsely coded under two separate dictionaries is made. Contextual information is considered by imposing superpixel-level joint sparsity constraints. In order to amplify the discrimination of the ship and clutter, we impose incoherence constraints between the two sub-dictionaries in the objective of feature coding. The discriminative dictionary is trained jointly with a linear classifier in task-driven dictionary learning (TDDL) framework. Based on the learnt dictionary and classifier, we extract discriminative features by sparse coding, and obtain robust detection results through binary classification. Different from previous methods, our ship detection cue is obtained through active learning strategies rather than artificially designed rules, and thus, is more adaptive, effective and robust. Experiments performed on synthetic images and two RADARSAT-2 images demonstrate that our method outperforms other comparative methods. In addition, the proposed method yields better shape-preserving ability and lower computation cost.

Steam explosion pretreatment was conducted on seabuckthom pomace. Response surface methodology was used to optimize the treatment conditions of steam explosion, including steam pressure, duration and particle size. After this, the content of total flavonoids and the antioxidant capacity of total flavonoids were investigated. Results showed that when the steam pressure was 2.0 MPa, duration was 88 s and a sieving mesh size was 60, the total flavonoids content in seabuckthorm reached a maximum of 24.74 ± 0.71 mg CAE/g, an increase of 246% compared with that without steam explosion treatment (7.14 ± 0.42 mg CAE/g). Also, DPPH and ·OH free radical scavenging ability showed significant improvement, with an IC50 decrease to 13.53 μg/mL and 4.32 μg/mL, respectively, far lower than that in original samples. Through the scanning electron microscope, the surface of seabuckthom pomace after steam explosion was crinkled, curly, and holey. Our study showed that the content of total flavonoids in seabuckthom pomace could be obviously promoted and the antioxidant capacity of total flavonoids also improved significantly, after applying steam explosion pretreatment to seabuckthom pomace, making this approach meaningful for the reuse of seabuckthom pomace resources.

Lightweight electromagnetic interference shielding cellulose foam/carbon fiber composites were prepared by blending cellulose foam solution with carbon fibers and then freeze drying. Two kinds of carbon fiber (diameter of 7 μm) with different lengths were used, short carbon fibers (SCF, L/D = 100) and long carbon fibers (LCF, L/D = 300). It was observed that SCFs and LCFs built efficient network structures during the foaming process. Furthermore, the foaming process significantly increased the specific electromagnetic interference shielding effectiveness from 10 to 60 dB. In addition, cellulose/carbon fiber composite foams possessed good mechanical properties and low thermal conductivity of 0.021⁻0.046 W/(m·K).

In the present study, the preliminary structure and in vitro antitumor activity of three exopolysaccharides (EPSs) from Streptococcus thermophilus CH9 were investigated. Then, three purified fractions of EPS-1a, EPS-2a, and EPS-3a were obtained by chromatography using DEAE-52 cellulose and Sephadex G-100, respectively. The average molecular weight of EPS-1a, EPS-2a, and EPS-3a, were 1.80 × 106, 1.06 × 106 and 1.05 × 106. The monosaccharide composition of EPS-3a was dramatically different from the others. The EPS-1a and EPS-2a were mainly composed of mannose, in a ratio of 69.82% and 57.09%, respectively, while EPS-3a was mainly composed of glucose (63.93%), without mannose. In addition, the surface morphology observed suggested that there were protein particles on the sugar chain of EPS-3a and EPS-3a was a protein-containing polysaccharide. Furthermore, EPS-3a exhibited higher antitumor activity against human liver cancer HepG2 cells in vitro. The antitumor activity of EPS-3a in HepG2 cells was associated with cell apoptosis. HE staining and Hoechst 33342 staining showed that with the treatment of EPS-3a, HepG2 cells had typical morphological changes. Flow cytometry analysis showed that the cell cycle was arrested at G0/G1 phase.

Accurate information on cropland changes is critical for food production and security, sustainable cropland management, and global change studies. The common change detection methods bi-temporal based, using remotely sensed imagery easily generate pseudo changes due to phenological or seasonal differences. Cropland exhibits a distinctive phenological trajectory that has strong periodic characteristics and seasonal paths. This paper proposes the use of phenological trajectory similarity to search for the overall changes between two time-series images instead of single change events between two dates of imagery. Due to the complex spectral–temporal characteristic of cropland, a phenological trajectory was constructed using a multi-harmonic model for capturing intra-annual variations. Then, phenological trajectory similarity was measured using coefficient vector difference (CVD), and used for detecting change/no-change areas when considering both the amplitude and phase difference. Finally, instead of the traditional classification method based on original images, we used the coefficient ratio vector (CRV) as the input for change type discrimination. The distance between the coefficient ratio vector (CRV) of the change pixel and of the reference change type was calculated to identify the exactly changed types. The performance of this proposed approach was tested using two sets of Landsat time-series images from 2010 and 2015. Moreover, the change area detection results of three other methods, namely, the continuous change detection and classification (CCDC), change vector analysis (CVA), and post-classification comparison (PCC), were also calculated for comparison and analysis. The results indicated that the proposed approach acquired the highest accuracy with an overall accuracy of 98.58% and a kappa coefficient of 0.82, which demonstrated that the method provides the capacity to detect real changes and estimate pseudo changes caused by season differences.