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Abstract Glioma is a common primary nervous system malignant tumor with poor overall cure rate and low survival rate, yet successful treatment still remains a challenge. Here, we demonstrated that amantadine (AMT) exhibits the powerful anti-glioma effect by promoting apoptosis and autophagy in vivo and in vitro. Mechanistically, amantadine induces a large amount of reactive oxygen species (ROS) accumulation in glioma cells, and then triggers apoptosis by destroying mitochondria. In addition, amantadine induces the initiation of autophagy and inhibits the fusion of autophagosome and lysosome, consequently performing an anti-glioma role. Taken together, our findings suggest that amantadine could be a promising anti-glioma drug that inhibits glioma cells by inducing apoptosis and autophagy, which may provide a novel potential treatment option for patients.

Abstract Pulsed polarized vortex beams, a special form of structured light, are generated by tailoring the light beam spatiotemporally and witness the growing application demands in nonlinear optics such as ultrafast laser processing and surface plasma excitation. However, existing techniques for generating polarized vortex beams suffer from either low compactness due to the use of bulky components or limited controlment of pulse performance. Here, an all-fiber technique combining plasmonic metafibers with mode conversion method is harnessed to generate high-performance pulsed polarized vortex beams. Plasmonic metafibers are utilized as saturable absorbers to produce Q-switched pulses with micro-second duration, while the offset splicing method is employed to partially convert the fundamental transverse mode (LP $$_{01}$$ 01 ) to higher-order mode (LP $$_{11}$$ 11 ). Eventually, a polarized vortex beams laser is achieved at the telecom band with a repetition frequency of 116.0 kHz. The impact of geometrical parameters including period of metafibers and offset of splicing on the spatiotemporal properties of pulsed polarized vortex beams is systematically investigated. Our findings could pave the way for design, control and generation of all-fiber pulsed polarized vortex beams, and also offer insights into the development of other types of structured laser sources.

This study investigates the effects of cold rolling and annealing on the microstructure, texture, and mechanical properties of FeCoCrNiMn high-entropy alloys. Utilizing vacuum induction melting, the alloy was initially cast into ingots and hot-rolled into plates, which were subsequently cold-rolled to various thicknesses and annealed at different temperatures. Microstructural analyses were conducted using X-ray diffraction and electron backscatter diffraction techniques, revealing a persistent face-centered cubic structure across all conditions. The texture evolution demonstrated a shift from Copper and S components to dominant Goss and Brass components as cold rolling intensified, suggesting the formation of Brass-type texture in FeCoCrNiMn at high deformation. Mechanical testing showed that the alloy's yield and tensile strengths significantly increased with cold rolling, reaching optimum values at ∼66 % reduction. Annealing at 750 °C enhanced both strength and ductility, primarily through grain refinement and the formation of Σ3 annealing twin boundaries, which dominated the microstructure of recrystallized grains. The study confirms that the low stacking fault energy of the alloy facilitates the activation of twinning and transformation-induced plasticity mechanisms, crucial for the observed enhancements in mechanical properties.

Abstract The three-stranded DNA-RNA triplex hybridization is involved in various biological processes, including gene expression regulation, DNA repair, and chromosomal stability. However, the DNA-RNA triplex mediating mechanisms underlying tumorigenesis remain to be fully elucidated. Here, we show that peptidylprolyl isomerase A (PPIA) serves as anchor to recruit GAU1 lncRNA by interacting with exon 4 of GAU1 and enhances the formation of SENP5/GAU1 DNA-lncRNA triplex. Intriguingly, TFR4 region of GAU1 exon 3 and TTS4 region of SENP5 promoter DNA constitute fragments forming the SENP5/GAU1 triplex. The SENP5/GAU1 triplex subsequently triggers the recruitment of the methyltransferase SET1A to exon 1 of GAU1, leading to the enrichment of H3K4 trimethylation and the activation of SENP5 transcription for driving the tumorigenesis of gastric cancer in vitro and in vivo. Our study reveals a mechanism of PPIA-guided SENP5/GAU1 DNA-lncRNA triplex formation in tumorigenesis and providing a concept in the dynamics of isomerase assisted DNA-RNA hybridization.

Abstract Background In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high‐level clinical evidence. This study aimed to compare the safety and long‐term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. Methods A prospective, single‐center, open‐label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event‐free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. Results Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1‐3M0 to T2‐3N0‐3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1‐year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1‐year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien‐Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment‐related AEs did not differ between the two groups (12.5% versus 12.4%). Conclusions The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

The Qizimeishan National Nature Reserve is situated in the southwestern region of Hubei Province, adjacent to the northeastern edge of the Yunnan-Guizhou Plateau. A survey of spiders of this reserve was conducted recently, leading to the discovery of three new species of the genus Pseudopoda Jäger, 2000: P. arcuata Zhang, J. Liu & Hu, sp. nov. (♀), P. qizimeishanensis Zhang, J. Liu & Hu, sp. nov. (♂, ♀) and P. weimiani Zhang, J. Liu & Hu, sp. nov. (♂, ♀). Diagnoses, descriptions, photos, and a distribution map are provided.

Abstract The spatial co-presence of aberrant long non-coding RNAs (lncRNAs) and abnormal coding genes contributes to malignancy development in various tumors. However, precise coordinated mechanisms underlying this phenomenon in tumorigenesis remains incompletely understood. Here, we show that Prohibitin 2 (PHB2) orchestrates the transcription of an oncogenic CASC15-New-Isoform 2 (CANT2) lncRNA and the coding tumor-suppressor gene CCBE1, thereby accelerating melanoma tumorigenesis. In melanoma cells, PHB2 initially accesses the open chromatin sites at the CANT2 promoter, recruiting MLL2 to augment H3K4 trimethylation and activate CANT2 transcription. Intriguingly, PHB2 further binds the activated CANT2 transcript, targeting the promoter of the tumor-suppressor gene CCBE1. This interaction recruits histone deacetylase HDAC1 to decrease H3K27 acetylation at the CCBE1 promoter and inhibit its transcription, significantly promoting tumor cell growth and metastasis both in vitro and in vivo. Our study elucidates a PHB2-mediated mechanism that orchestrates the aberrant transcription of lncRNAs and coding genes, providing an intriguing epigenetic regulatory model in tumorigenesis.

Abstract Background Wheat (Triticum aestivum L.) is an important grain crops in the world, and its growth and development in different stages is seriously affected by saline-alkali stress, especially in seedling stage. Therefore, nondestructive detection of wheat seedlings under saline-alkali stress can provide more comprehensive technical support for wheat breeding, cultivation and management. Results This research focused on moisture signal prediction and classification of saline-alkali stress in wheat seedlings using fusion techniques. After collecting and analyzing transverse relaxation time and Multispectral imaging (MSI) information of wheat seedlings, four regression models were used to predict the moisture signal. K-Nearest Neighbor (KNN) and Gaussian-Naïve Bayes (GNB) models were combined with fivefold cross validation to classify the prediction of wheat seedling stress. The results showed that wheat seedlings would increase the bound water content through a certain mechanism to enhance their saline-alkali stress. Under the same Na concentration, the effect of alkali stress on moisture, growth and spectrum of wheat seedlings is stronger than salt stress. The Gradient Boosting Decision Regression Tree model performs the best in predicting wheat moisture signals, with a coefficient of determination (R2P) of 0.98 and a root mean square error of 109.60. It also had a short training time (1.48 s) and an efficient prediction speed (1300 obs/s). The KNN and GNB demonstrated significantly enhanced predictive performance when classifying the fused dataset, compared to using single datasets individually. In particular, the GNB model performing best on the fused dataset, with Precision, Recall, Accuracy, and F1-score of 90.30, 88.89%, 88.90%, and 0.90, respectively. Conclusions Under the same Na concentration, the effects of alkali stress on water content, spectrum, and growth of wheat were stronger than that of salt stress, which was more unfavorable to the growth of wheat. The fusion of low-field nuclear magnetic resonance and MSI technology can improve the classification of wheat stress, and provide an effective technical method for rapid and accurate monitoring of wheat seedlings under saline-alkali stress. Graphical Abstract

Abstract Background Dengue virus (DENV) is the most widespread arbovirus. The World Health Organization (WHO) declared dengue one of the top 10 global health threats in 2019. However, it has been underrepresented in bibliometric analyses. This study employs bibliometric analysis to identify research hotspots and trends, offering a comprehensive overview of the current research dynamics in this field. Results We present a report spanning from 1995 to 2023 that provides a unique longitudinal analysis of Dengue virus (DENV) research, revealing significant trends and shifts not extensively covered in previous literature. A total of 10,767 DENV-related documents were considered, with a notable increase in publications, peaking at 747 articles in 2021. Plos Neglected Tropical Diseases has become the leading journal in Dengue virus research, publishing 791 articles in this field—the highest number recorded. Our bibliometric analysis provides a comprehensive mapping of DENV research across multiple dimensions, including vector ecology, virology, and emerging therapies. The study delineates a complex network of immune response genes, including IFNA1, DDX58, IFNB1, STAT1, IRF3, and NFKB1, highlighting significant trends and emerging themes, particularly the impacts of climate change and new outbreaks on disease transmission. Our findings detail the progress and current status of key vaccine candidates, including the licensed Dengvaxia, newer vaccines such as Qdenga and TV003, and updated clinical trials. The study underscores significant advancements in antiviral therapies and vector control strategies for dengue, highlighting innovative drug candidates such as AT-752 and JNJ-1802, and the potential of drug repurposing with agents like Ribavirin, Remdesivir, and Lopinavir. Additionally, it discusses biological control methods, including the introduction of Wolbachia-infected mosquitoes and gene-editing technologies. Conclusion This bibliometric study underscores the critical role of interdisciplinary collaboration in advancing DENV research, identifying key trends and areas needing further exploration, including host-virus dynamics, the development and application of antiviral drugs and vaccines, and the use of artificial intelligence. It advocates for strengthened partnerships across various disciplines to effectively tackle the challenges posed by DENV.

Introduction: The association between elevated lactate levels and the development of disseminated intravascular coagulation (DIC) in patients with severe trauma remains unclear. Hence, this study aimed to explore the association between lactate and the development of DIC in patients with severe trauma. Methods: This prospective cohort study was conducted on consecutive patients with severe trauma who were hospitalized in the intensive care unit from January 2020 to January 2023. The primary outcome measured was the occurrence of DIC in patients in the emergency department or posthospitalization. Logistic regression analysis evaluating the risk values for lactate and DIC, the receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) examinations studying the predictive efficiency of lactate for DIC. The Kaplan–Meier survival curve was used to assess patient survival. Sensitivity robustness analysis included modified Poisson regression, E-value, subgroup analysis, and numerical variable transformation analysis. Results: Logistic regression analysis corrected for confounding factors showed that lactate was a risk factor for DIC in patients with severe trauma (adjusted odds ratio [OR]: 1.374, 95% confidence interval [CI]: 1.206–1.566). Lactate predicted DIC risk with a 0.8513 area under the ROC curve (95% CI: 0.7827–0.9199), 4.8 cutoff value, 0.8333 sensitivity, and 0.8014 specificity. DCA showed the correlation between lactate and DIC. The mortality rate of patients with a high risk of DIC was significantly higher than that of patients with a low risk (log-rank test, P < 0.001). The modified Poisson regression showed that lactate was a risk factor for DIC (risk ratio: 1.188, 95% CI: 1.140–1.237). E-value was 1.645, and the lower limit of 95% CI was 1.495. The logistic regression analysis after subgroup analysis and transformation of numerical variables showed that lactate remained a risk factor for DIC. Conclusions: Elevated lactate is closely associated with the occurrence of DIC in patients with severe trauma. Lactate seems to be a good predictive factor for DIC manifestation in patients with severe trauma.

Abstract Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.

Abstract Background Tubal mesosalpinx cysts are paratubal cysts, that account for approximately 10% of adnexal masses, and the presence of these cysts combined with adnexal torsion is a rare acute abdominal condition, with few cases reported in the literature. We reported two cases of adolescent tubal mesosalpinx cysts combined with adnexal torsion and reviewed the literature to help improve the diagnosis of the disease. Case reports The first patient was an 11-year-old girl with left lower abdominal pain for 5 days and fever with nausea and vomiting for 3 days, who was found to have a cystic pelvic mass on preoperative imaging and was diagnosed intraoperatively and postoperatively on pathology as having a left tubal mesosalpinx cyst combined with adnexal torsion. The second patient was a 13-year-old girl with right lower abdominal pain for 16 h and a palpable mass in the lower and middle abdomen on examination, which was hard and tender to palpate. Preoperative imaging revealed a large cystic mass in the right adnexal region, and intraoperative and postoperative pathology revealed a right tubal mesosalpinx cyst combined with adnexal torsion. Conclusions Tubal mesosalpinx cysts combined with adnexal torsion are rare causes of acute lower abdominal pain. Early diagnosis and timely surgery are necessary to ensure ovarian and tubal function. Accurate preoperative imaging diagnosis is challenging, and MRI is a beneficial supplement to ultrasound and CT examinations, providing more objective imaging information and reducing the incidence of adverse outcomes.

Highlights A novel organohydrogel-based multimodal e-skin with excellent sensing performance for temperature, humidity, pressure, proximity, and NO2 is proposed for the first time, showing powerful sensing capabilities beyond natural skin. The developed multimodal e-skin exhibited extraordinary sensing performance at room temperature, including fast pressure response time (0.2 s), high temperature sensitivity (9.38% °C-1), a wide range of humidity response (22%–98% RH), high NO2 sensitivity (254% ppm-1), a low detection limit (11.1 ppb NO2) and the abilities to sense the proximity of objects accurately, which are yet achieved by previous e-skins. The multimodal e-skin was combined with the deep neural network algorithm and wireless alarm circuit to achieve zero-error classification of different objects and rapid response to NOx leak incidents, proving the feasibility of the e-skin-assisted rescue robot for post-earthquake rescue.

Abstract Background Pruning is an important cultivation management option that has important effects on peach yield and quality. However, the effects of pruning on the overall genetic and metabolic changes in peach leaves and fruits are poorly understood. Results The transcriptomic and metabolomic profiles of leaves and fruits from trees subjected to pruning and unpruning treatments were measured. A total of 20,633 genes and 622 metabolites were detected. Compared with those in the control, 1,127 differentially expressed genes (DEGs) and 77 differentially expressed metabolites (DEMs) were identified in leaves from pruned and unpruned trees (pdLvsupdL), whereas 423 DEGs and 29 DEMs were identified in fruits from the pairwise comparison pdFvsupdF. The content of three auxin analogues was upregulated in the leaves of pruned trees, the content of all flavonoids detected in the leaves decreased, and the expression of almost all genes involved in the flavonoid biosynthesis pathway decreased. The phenolic acid and amino acid metabolites detected in fruits from pruned trees were downregulated, and all terpenoids were upregulated. The correlation analysis revealed that DEGs and DEMs in leaves were enriched in tryptophan metabolism, auxin signal transduction, and flavonoid biosynthesis. DEGs and DEMs in fruits were enriched in flavonoid and phenylpropanoid biosynthesis, as well as L-glutamic acid biosynthesis. Conclusions Pruning has different effects on the leaves and fruits of peach trees, affecting mainly the secondary metabolism and hormone signalling pathways in leaves and amino acid biosynthesis in fruits.

Abstract Objective Sarcopenia is a geriatric syndrome that occurs with age and is characterized by a gradual decline in muscle mass, power, and functionality. It serves as a prominent contributor to frailty, disability, and mortality among older individuals. Currently, no standardized global guidelines exist for the diagnosis of sarcopenia. This study aimed to establish the correlation between sarcopenia and the constitutions of traditional Chinese medicine (TCM), considering the connection between physical functioning and sarcopenia. Methods A total of 1441 participants in this study were diagnosed with sarcopenia. The Asian Working Group for Sarcopenia (AWGS) proposed a sarcopenia definition algorithm. To determine the constitution of each participant, classification and determination standards were used in traditional Chinese medicine. This study evaluated the demographics, lifestyles, and self‐reported medical history of individuals diagnosed with sarcopenia through a self‐administered questionnaire. The constitution of the participants was determined using TCM classification and determination standards. Subsequently, we analyzed the results of univariate analysis and multivariate regression and constructed a receiver operating characteristic (ROC) curve. Results Participants who were diagnosed with sarcopenia had substantially lower original Neutral constitution scores (P

Abstract Gridization is an emerging molecular integration technology that enables the creation of multifunctional organic semiconductors through precise linkages. While Friedel-Crafts gridization of fluorenols is potent, direct linkage among fluorene molecules poses a challenge. Herein, we report an achiral Pd-PPh3-cataylized diastereoselective (>99:1 d.r.) gridization based on the C-H-activation of fluorene to give dimeric and trimeric windmill-type nanogrids (DWGs and TWGs). These non-conjugated stereo-nanogrids showcase intramolecular multiple H…H interactions with a low field shift to 8.51 ppm and circularly polarized luminescence with high luminescent dissymmetry factors (|g PL | = 0.012). Significantly, the nondoped organic light-emitting diodes (OLEDs) utilizing cis-trans-TWG1 emitter present an ultraviolet electroluminescent peak at ~386 nm (CIE: 0.17, 0.04) with a maximum external quantum efficiency of 4.17%, marking the highest record among nondoped ultraviolet OLEDs based on hydrocarbon compounds and the pioneering ultraviolet OLEDs based on macrocycles. These nanohydrocarbon offer potential nanoscafflolds for ultraviolet light-emitting optoelectronic applications.

Abstract Background Plant microbiota contributes to plant growth and health, including enhancing plant resistance to various diseases. Despite remarkable progress in understanding diseases resistance in plants, the precise role of rhizosphere microbiota in enhancing watermelon resistance against soil-borne diseases remains unclear. Here, we constructed a synthetic community (SynCom) of 16 core bacterial strains obtained from the rhizosphere of grafted watermelon plants. We further simplified SynCom and investigated the role of bacteria with synergistic interactions in promoting plant growth through a simple synthetic community. Results Our results demonstrated that the SynCom significantly enhanced the growth and disease resistance of ungrafted watermelon grown in non-sterile soil. Furthermore, analysis of the amplicon and metagenome data revealed the pivotal role of Pseudomonas in enhancing plant health, as evidenced by a significant increase in the relative abundance and biofilm-forming pathways of Pseudomonas post-SynCom inoculation. Based on in vitro co-culture experiments and bacterial metabolomic analysis, we selected Pseudomonas along with seven other members of the SynCom that exhibited synergistic effects with Pseudomonas. It enabled us to further refine the initially constructed SynCom into a simplified SynCom comprising the eight selected bacterial species. Notably, the plant-promoting effects of simplified SynCom were similar to those of the initial SynCom. Furthermore, the simplified SynCom protected plants through synergistic effects of bacteria. Conclusions Our findings suggest that the SynCom proliferate in the rhizosphere and mitigate soil-borne diseases through microbial synergistic interactions, highlighting the potential of synergistic effects between microorganisms in enhancing plant health. This study provides a novel insight into using the functional SynCom as a promising solution for sustainable agriculture. Video Abstract

IntroductionStreptococcus suis (SS) is one of the most important pathogens causing major economic losses in the global pig farming industry and is a serious threat to public health safety. It has multiple serotypes, with poor cross-protection between serotypes, and effective typing methods are lacking.MethodsIn this study, a quadruplex TaqMan fluorescence quantitative PCR assay that can differentiate between Streptococcus suis types 2, 7 and 9 was developed using the gdh gene, a generic gene for Streptococcus suis, and cps2J, cps7H and cps9J, genes encoding podocarp-associated genes for types 2, 7 and 9, respectively, as targets.ResultsThe method is specific enough to accurately type Streptococcus suis pigmentosus without detecting non-target pathogens (Escherichia coli, Pasteurella multocida, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae and et al). The sensitivity was high, with a minimum lower detection line of 10 copies for P-SS and P-SS9, and 100 copies for P-SS2 and P-SS7. The standard curves generated showed good linearity with R2 of 0.999, 0.999, 0.997 and 0.998 respectively. The repeatability was good, with coefficients of variation between batch to batch and batch to batch tests ranging from 0.21% to 1.10%. Testing of 156 samples yielded 68 positive and 88 negative samples, of which the positive rate of SS was 5.77% (9/156), SS2 was 20.51% (32/156), SS7 was 8.33% (13/156) and SS9 was 9.6% (15/156), which was in line with the existing fluorescent quantitative PCR assay of 93.75%~100%, which was higher than the detection rate of conventional PCR.DiscussionThe quadruplex TaqMan fluorescence quantitative PCR method of Streptococcus suis generic, type 2, 7 and 9 established in this study can accurately differentiate the three serotypes of Streptococcus suis that currently have high prevalence and pathogenicity, which is of great importance for accurate clinical prevention and treatment, epidemiological investigation and vaccine development.

ABSTRACT The interactions between hosts and the gut microbiota are intricate and can significantly affect the ecology and evolution of both parties. Various host traits, including taxonomy, diet, social behaviour, and external factors such as prey availability and the local environment, all play an important role in shaping composition and diversity of the gut microbiogta. In this study, we explored the impact of intestinal microorganisms on the host in adapting to their respective ecological niches in two species of snakes. We collected feces from Lycodon rufozonatus and Lycodon rosozonatus from different geographical locations and used 16S rRNA gene sequencing technology to sequence the v3‐v4 region. The results revealed that there was no significant difference in the alpha diversity of intestinal microorganisms between L. rufozonatus and L. rosozonatus. The gut microbiota of all individuals comprised four main phyla: Pseudomonadota, Bacteroidota, Bacillota, and Actinomycetota. At the genus level, the genus Salmonella dominated the enterobacterial microbiota in the samples from Hainan, while there was no obvious dominant genus in the enterobacterial microbiota of the samples from the other four localities. Comparative analysis of enzyme families annotated to the gut microbiota between L. rufozonatus and L. rosozonatus from the four sampling regions by CAZy carbohydrate annotation revealed that nine enzyme families differed significantly in terms of glycoside hydrolases (GHs). In addition, we compared the composition of gut microbial communities between L. rufozonatus and L. rosozonatus and investigated the impact of the differences on their functions. Our results will provide insights into the coevolution of host and gut microbes.

ABSTRACT Altered composition of the gut microbiota affects immunity and metabolism. This study previously found that eIF6 gene knockdown changes the composition of the intestinal flora in the eIF6 gene knockdown mouse model. Lactobacillus acidophilus is significantly increased in the model. This study was designed to investigate the role of L. acidophilus in the pathogenesis of atherosclerosis. Transcriptomic data from 117 patients with coronary artery disease (CAD) and 79 healthy individuals were obtained. ApoE−/− and ApoE−/−/eIF6+/− mice on normal chow diet or a high-fat diet were treated for 16 weeks; eIF6 deficiency was evaluated atherosclerosis. ApoE−/− mice on normal chow diet or a high-fat diet were treated with L. acidophilus by daily oral gavage for 16 weeks. Moreover, one group was treated with lipopolysaccharide at 12 weeks. The levels of eIF6, RNASE3, and RSAD2 were notably higher in the patients with CAD than in the healthy individuals. eIF6 deficiency altered the composition of gut microbiota. eIF6 deficiency reduced the atherosclerotic lesion formation in ApoE−/−/eIF6+/− mice compared with the ApoE−/− mice. The microbial sequencing and metabolomics analysis demonstrated some beneficial bacterial (L. acidophilus, Ileibacterium, and Bifidobacterium) and metabolic levels significantly had deference in ApoE−/−/eIF6+/− mice compared with the ApoE−/− mice. Correlational studies indicated that L. acidophilus had close correlations with low-density lipoprotein cholesterol, lesion area, and necrotic area. L. acidophilus inhibited high-fat diet-induced inflammation and atherosclerotic lesion, increasing the expression of tight junction proteins (ZO-1 and claudin-1) and reducing the gut permeability. However, lipopolysaccharide reversed the protective effect of L. acidophilus against atherosclerosis. eIF6 deficiency protected against atherosclerosis by regulating the composition of gut microbiota and metabolites. L. acidophilus attenuated atherosclerotic lesions by reducing inflammation and increasing gut permeability.IMPORTANCEeIF6 deficiency modulates the gut microbiota and multiple metabolites in atherosclerotic ApoE−/− mice. L. acidophilus was reduced in the gut of atherosclerotic ApoE−/− mice, but administration of Lactobacillus acidophilus reversed intestinal barrier dysfunction and vascular inflammation. Our findings suggest that targeting individual species is a beneficial therapeutic strategy to prevent inflammation and atherosclerosis.

Struma ovarii (SO) represents a rare subset of ovarian germ cell tumors, with approximately 5% transforming into malignant SO (MSO). This study retrospectively analyzed clinical data from 23 SO patients treated at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2013 and December 2023, including 17 benign SO (BSO) and 6 MSO cases. Additionally, a systematic review of 164 cases of MSO confined to the ovary, reported in the literature from 1946 to 2024, was conducted. Data on pathological type, treatment, and prognosis were extracted, and univariate and multivariate Cox regression analyses were performed to identify risk factors for recurrence in stage I MSO. The median age at diagnosis was higher for BSO compared to MSO (58 vs. 42.5 years), with 70.6% of patients being postmenopausal. BSO commonly presented with abdominal distension or mass, with more than half having ascites, while MSO patients were asymptomatic and lacked ascites. Cox regression analyses revealed that ovarian cystectomy was adversely associated with recurrence risk in stage I MSO, likely due to surgically induced capsular rent and potential tumor spillage. Significantly lower recurrence risks were observed in patients who underwent unilateral or bilateral salpingo-oophorectomy (HR = 0.36, P = 0.019; HR = 0.19, P = 0.004, respectively). This study highlights the importance of the surgical approach in the management of stage I MSO. A thorough preoperative discussion of the benefits and risks of different surgical approaches is recommended for patients desiring fertility preservation. Postoperative adjuvant therapy has not been shown to have a significant impact on prognosis. For the treatment of recurrent MSO, selecting appropriate surgical and adjuvant therapeutic strategies is essential to improve the long-term prognosis of MSO patients.

Retinal surgery requires enclosed spatial constraints to improve the safety and success of the surgery. Herein, a shared control method is proposed for master–slave robot systems, utilizing tubular guidance constraints based on a novel potential field function to optimize the commands of the surgeon. Within the tube, attractive constraints intensify with increasing task error and approach infinity at the boundary of the tube. This ensures that the surgery is confined within a closed tubular space. Haptic feedback provides force cues to inform the surgeon about the feasibility of the input commands. Theoretical derivations demonstrate that the entire closed‐loop system is passive. Two simulation experiments are conducted on the ophthalmic surgery robot platform to evaluate the functionality of the proposed method. The experimental results indicate that translational errors are kept less than certain predefined values. Furthermore, the proposed method outperforms the comparison method in terms of task accuracy and efficiency.

Abstract Three novel asymmetric Ir(III) complexes have been rationally designed to optimize their emitting dipole orientations (EDO) and enhance light outcoupling in blue phosphorescent organic light‐emitting diodes (OLEDs), thereby boosting their external quantum efficiency (EQE). Bulky electron‐donating groups (EDGs), namely: carbazole (Cz), di‐tert‐butyl carbazole (tBuCz), and phenoxazine (Pxz) are incorporated into the tridentate dicarbene pincer chelate to induce high degree of packing anisotropy, simultaneously enhancing their photophysical properties. Angle‐dependent photoluminescence (ADPL) measurements indicate increased horizontal transition dipole ratios of 0.89 and 0.90 for the Ir(III) complexes Cz‐dfppy‐CN and tBuCz‐dfppy‐CN, respectively. Analysis of the single crystal structure and density functional theory (DFT) calculation results revealed an inherent correlation between molecular aspect ratio and EDO. Utilizing the newly obtained emitters, the blue OLED devices demonstrated exceptional performance, achieving a maximum EQE of 30.7% at a Commission International de l'Eclairage (CIE) coordinate of (0.140, 0.148). Optical transfer matrix‐based simulations confirmed a maximum outcoupling efficiency of 35% due to improved EDO. Finally, the tandem OLED and hyper‐OLED devices exhibited a maximum EQE of 44.2% and 31.6%, respectively, together with good device stability. This rational molecular design provides straightforward guidelines to reach highly efficient and stable saturated blue emission.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major thread to the global swine industry, lack of effective control strategies. This study explores the regulatory role of a small non-coding RNA, miR-191-5p, in PRRSV infection. We observed that miR-191-5p significantly inhibits PRRSV in porcine alveolar macrophages (PAMs), contrasting with negligible effects in MARC-145 and HEK293-CD163 cells, suggesting a cell-specific antiviral effect. Further investigation unveiled that miR-191-5p directly targets the porcine epidermal growth factor receptor (EGFR), whose overexpression or EGF-induced activation suppresses type I interferon (IFN-I) signaling, promoting PRRSV replication. In contrast, siRNA-or miR-191-5p-induced EGFR downregulation or EGFR inhibitor boosts IFN-I signaling, reducing viral replication. Notably, this miRNA alleviates the suppressive effect of EGF on IFN-I signaling, underscoring its regulatory function. Further investigation revealed interconnections among miR-191-5p, EGFR and signal transducer and activator of transcription 3 (STAT3). Modulation of STAT3 activity influenced IFN-I signaling and PRRSV replication, with STAT3 knockdown countering EGFR activation-induced virus replication. Combination inhibition of STAT3 and miR-191-5p suggests that STAT3 acts downstream in EGFR’s antiviral response. Furthermore, miR-191-5p’s broad efficacy in restricting various PRRSV strains in PAMs was identified. Collectively, these findings elucidate a novel mechanism of miR-191-5p in activating host IFN-I signaling to inhibit PRRSV replication, highlighting its potential in therapeutic applications against PRRSV.

IntroductionIn maize and peanut intercropping, shading emerges as a critical factor for restricting peanut growth, yield, and quality.MethodsThis study investigated the impact of 30% shade on shade-tolerant [Huayu 22 (HY22) and Fuhua 12 (FH12)] and shade-sensitive [Nonghua 11 (NH11) and Nonghua 5(NH5)] peanut varieties, with non-shaded condition as the control (CK). The effects of shade stress on plant morphology, photosynthetic characteristics, dry-matter accumulation, chloroplast ultra-microstructure, yield, and quality of different shade-tolerant peanut varieties were examined.ResultsCompared to that in the control, shade stress led to an elongation of the main stem, shortening of the lateral branches, and reduction in the leaf area. However, these changes were less significant in the shade-tolerant than in the shade-sensitive peanut varieties, with minimal effect on the elongation of the main stem height and shortening of the lateral branches. Differences in leaf area became significant during the later stages of shade stress, particularly pronounced in the shade-sensitive peanut varieties. To enhance light capture by leaves, the shade-tolerant peanut varieties exhibited increased chlorophyll content and chloroplast grain-layer numbers. The decrease in the chlorophyll a/b ratio was more pronounced in the shade-tolerant than in the shade-sensitive peanut varieties, with significant differences. However, reduced activities of ribulose 1,5-biphosphate (RuBP) carboxylase/oxygenase and fructose 1,6-biphosphate aldolase (FBA) resulted in decreased net photosynthetic rates, particularly evident in the shade-sensitive peanut varieties during the late shade period. Shade stress led to decreased dry-matter accumulation, reduced weight of 100 fruits and kernels, and a significant decline in yield in the shade-sensitive cultivars. Shading also affected peanut-kernel quality. Compared with that in the control, the protein content increased and amino-acid (except cysteine) content decreased in the shade-tolerant cultivars.DiscussionUnder shade stress, shade tolerant peanut varieties have increased the yield by improving the photosynthetic efficiency, which provided a reference for rational selection of shade tolerant peanut varieties in maize and peanut intercropping system.

Quinoa is an annual dicotyledonous plant belonging to the genus Chenopodiaceae. As a functional healthy food with outstanding nutritional value, quinoa contains not only a balanced proportion of amino acids but also higher contents of protein, unsaturated fatty acids, vitamins, and minerals (K, P, Mg, Ca, Zn, and Fe) than most cereal crops. Quinoa is also rich in active ingredients, such as polyphenols, flavonoids, saponins, polysaccharides, peptides, and ecdysone, which provide balanced nutrition, enhance the body function, regulate blood sugar, decrease blood lipid, increase anti-oxidation and anti-inflammatory action, and prevent and treat cardiovascular diseases. Thus, quinoa is especially suitable for people suffering from chronic diseases, such as diabetes, hypertension, hyperlipidemia, and heart disease, and for the elderly people. Because of its comprehensive nutritional value and edible functional characteristics, quinoa is better than most grains and has become a highly nutritious food suitable for human consumption. This article reviews the active ingredients and physiological functions of quinoa, aiming to provide a reference for further research and its utilization in food, healthcare, and pharmaceutical research and development.

ABSTRACT The intact immune system of mice exhibits resistance to colonization by exogenous microorganisms, but the gut microbiota profiles of the humanized mice and the patterns of human fecal microbiota colonization remain unexplored. Humanized NCG (huNCG) mice were constructed by injected CD34 +stem cells. 16S rRNA sequencing and fecal microbiota transplantation (FMT) technologies were used to detect the differences in microbiota and selective colonization ability for exogenous community colonization among three mice cohorts (C57BL/6J, NCG, and huNCG). Flow cytometry analysis showed that all huNCG mice had over 25% hCD45 +in peripheral blood. 16S rRNA gene sequence analysis showed that compared with NCG mice, the gut microbiota of huNCG mice were significantly altered. After FMT, the principal coordinates analysis (PCoA) showed that the gut microbial composition of huNCG mice (huNCG-D9) was similar to that of donors. The relative abundance of Firmicutes and Bacteroidetes were significantly increased in huNCG mice compared to NCG mice. Further comparison of ASV sequences revealed that Bacteroides plebeius, Bacteroides finegoldii, Escherichia fergusonii, Escherichia albertii, Klebsiella pneumoniae, and Klebsiella variicola exhibited higher abundance and stability in huNCG mice after FMT. Furthermore, PICRUSt2 analysis showed that huNCG mice had significantly enhanced metabolism and immunity. This study demonstrated that humanized mice are more conducive to colonization within the human gut microbiota, which provides a good method for studying the association between human diseases and microbiota.IMPORTANCEThe gut microbiota and biomarkers of humanized mice are systematically revealed for the first time. The finding that human fecal microbiota colonize humanized mice more stably provides new insights into the study of interactions between immune responses and gut microbiota.

IntroductionOsteoarthritis (OA) is a prevalent chronic degenerative disease, marked by a complex interplay of mechanical stress, inflammation, and metabolic imbalances. Recent studies have highlighted the potential of spermidine (SPD), a naturally occurring polyamine known for its anti-inflammatory and antioxidant properties, as a promising therapeutic agent for OA. This study delves into the therapeutic efficacy and mechanistic pathways of SPD in mitigating OA symptoms.MethodsForty Sprague-Dawley rats were randomly assigned to four groups, including the CG (sham operation), model (anterior cruciate ligament transection [ACLT], and treatment (ACLT + two different doses of SPD) groups. In vivo, correlations between OA severity and different interventions were assessed by ELISA, X-rays, CT imaging, histological staining, and immunohistochemistry. In vitro, IL-1β was used to trigger chondrocyte inflammation, and SPD’s cytotoxicity was assessed in primary rat chondrocytes. Next, inflammatory markers, extracellular matrix (ECM) proteins, and pathway marker proteins were detected in chondrocytes administered IL-1β alone, SPD, or aryl hydrocarbon receptor (AhR) silencing, by qRT-PCR, Griess reaction, ELISA, Western blot, and immunofluorescence. Morphological alterations and pyroptosis in chondrocytes were examined by transmission electron microscopy (TEM) and flow cytometry.ResultsOur research reveals that SPD exerts significant anti-inflammatory and antipyroptotic effects on IL-1β-treated chondrocytes and in anterior cruciate ligament transection (ACLT) rat models of OA, primarily through interaction with the Aryl hydrocarbon receptor (AhR). Specifically, SPD’s binding to AhR plays a crucial role in modulating the inflammatory response and cellular pyroptosis by inhibiting both the AhR/NF-κB and NLRP3/caspase-1/GSDMD signaling pathways. Furthermore, the knockdown of AhR was found to negate the beneficial effects of SPD, underscoring the centrality of the AhR pathway in SPD’s action mechanism. Additionally, SPD was observed to promote the preservation of cartilage integrity and suppress ECM degradation, further supporting its potential as an effective intervention for OA.DiscussionCollectively, our findings propose SPD as a novel therapeutic approach for OA treatment, targeting the AhR pathway to counteract the disease’s progression and highlighting the need for further clinical evaluation to fully establish its therapeutic utility.

IntroductionIn riverine ecosystems, dynamic interplay between hydrological conditions, such as flow rate, water level, and rainfall, significantly shape the structure and function of bacterial and microeukaryotic communities, with consequences for biogeochemical cycles and ecological stability. Lake Taihu, one of China’s largest freshwater lakes, frequently experiences cyanobacterial blooms primarily driven by nutrient over-enrichment and hydrological changes, posing severe threats to water quality, aquatic life, and surrounding human populations. This study explored how varying water flow disturbances influence microbial diversity and community assembly within the interconnected river–lake systems of the East and South of Lake Taihu (ET&ST). The Taipu River in the ET region accounts for nearly one-third of Lake Taihu’s outflow, while the ST region includes the Changdougang and Xiaomeigang rivers, which act as inflow rivers. These two rivers not only channel water into Lake Taihu but can also cause the backflow of lake water into the rivers, creating distinct river–lake systems subjected to different intensities of water flow disturbances.MethodsUtilizing high-throughput sequencing, we selected 22 sampling sites in the ET and ST interconnected river-lake systems and conducted seasonally assessments of bacterial and microeukaryotic community dynamics. We then compared differences in microbial diversity, community assembly, and co-occurrence networks between the two regions under varying hydrological regimes.Results and discussionThis study demonstrated that water flow intensity and temperature disturbances significantly influenced diversity, community structure, community assembly, ecological niches, and coexistence networks of bacterial and eukaryotic microbes. In the ET region, where water flow disturbances were stronger, microbial richness significantly increased, and phylogenetic relationships were closer, yet variations in community structure were greater than in the ST region, which experienced milder water flow disturbances. Additionally, migration and dispersal rates of microbes in the ET region, along with the impact of dispersal limitations, were significantly higher than in the ST region. High flow disturbances notably reduced microbial niche width and overlap, decreasing the complexity and stability of microbial coexistence networks. Moreover, path analysis indicated that microeukaryotic communities exhibited a stronger response to water flow disturbances than bacterial communities. Our findings underscore the critical need to consider the effects of hydrological disturbance on microbial diversity, community assembly, and coexistence networks when developing strategies to manage and protect river–lake ecosystems, particularly in efforts to control cyanobacterial blooms in Lake Taihu.

Abstract Stretchable electrodes based on liquid metals (LM) are widely used in human‐machine interfacing, wearable bioelectronics, and other emerging technologies. However, realizing the high‐precision patterning and mechanical stability remains challenging due to the poor wettability of LM. Herein, a method is reported to fabricate LM‐based multilayer solid–liquid electrodes (m‐SLE) utilizing electrohydrodynamic (EHD) printed confinement template. In these electrodes, LM self‐assembled onto these high‐resolution templates, assisted by selective wetting on the electrodeposited Cu layer. This study shows that a m‐SLE composed of PDMS/Ag/Cu/EGaIn exhibits line width of ≈20 µm, stretchability of ≈100%, mechanical stability ≈10 000 times (stretch/relaxation cycles), and recyclability. The multi‐layer structure of m‐SLE enables the adjustability of strain sensing, in which the strain‐sensitive Ag part can be used for non‐distributed detection in human health monitoring and the strain‐insensitive EGaIn part can be used as interconnects. In addition, this study demonstrates that near field communication (NFC) devices and multilayer displays integrated by m‐SLEs exhibit stable wireless signal transmission capability and stretchability, suggesting its applicability in creating highly‐integrated, large‐scale commercial, and recyclable wearable electronics.

IntroductionOsteosarcoma is a common type of bone cancer characterized by a poor prognosis due to its metastatic nature. The tumor microenvironment (TME) plays a critical role in tumor metastasis and therapy response. Therefore, our study aims to explore the metastatic mechanism of osteosarcoma, potentially opening new avenues for cancer treatment.MethodsIn this study, we collected data from the GSE152048, GSE14359, and GSE49003 datasets. Differentially expressed genes (DEGs) were identified in osteosarcoma cases with primary and metastatic features using R software and the limma package. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate metastasis-related genes. A protein–protein interaction (PPI) network was established using the STRING database to further analyze these metastasis-associated genes. The abundances of different cell types with a mixed cell population were estimated using the CIBERSORT approach. The scRNA-seq data were analyzed by the Seurat package in R software, and intercellular communications were elucidated using the CellChat R package.ResultsIn this study, 92 DEGs related to metastasis were identified, including 41 upregulated and 51 downregulated genes in both the GSE14359 and GSE49003 datasets. Metastasis-associated pathways were identified, including those involving the cyclin-dependent protein kinase holoenzyme complex, transferase complex, transferring phosphorus-containing groups, SCF ubiquitin ligase complex, and the serine/threonine protein kinase complex. KEGG and PPI network analyses revealed 15 hub genes, including Skp2, KIF20A, CCNF, TROAP, PHB, CKS1B, MCM3, CCNA2, TRIP13, CENPM, Hsp90AB1, JUN, CKS2, TK1, and KIF4A. Skp2 has been known as an E3 ubiquitin ligase involved in osteosarcoma progression. The proportion of CD8+ T cells was found to be higher in metastatic osteosarcoma tissues, and high expression of PHB was associated with a favorable prognosis in osteosarcoma patients. Additionally, 23 cell clusters were classified into eight cell types, including chondrocytes, MSC, T cells, monocytes, tissue stem cells, neurons, endothelial cells, and macrophages. The 15 hub genes were expressed across various cell types, and interactions between different cell types were observed.ConclusionOur study reveals the intricate communication between tumor microenvironment components and tumor metastasis in osteosarcoma.

To improve the reliability of the incremental dynamic analysis, the Monte Carlo simulation technique is introduced to fully consider the uncertainties in the characteristics of earthquakes. To match the computational efficiency of Monte Carlo simulation, structural seismic responses are calculated by neural networks. To consider the failure risks under 3 safety requirements imposed on the structural seismic performance by the Chinese standard, the equivalent failure probability is employed to compare the safety of 4 different design schemes composed of high-rise frame structures. The workflow of the proposed method is demonstrated by taking the 4 design schemes as examples; good agreement is found between the failure probabilities of the entire structures and their stories with their failure states. Furthermore, the safety of these schemes is compared, and some design advice is discussed.

With 252 species, Pseudopoda Jäger, 2000, is the largest genus in the family Sparassidae and is widely distributed in South (49 species in Bhutan, India, Nepal and Pakistan), East (158 species in China and Japan) and Southeast Asia (51 species in Indonesia, Laos, Myanmar, Thailand and Vietnam). Few species have been found in more than one region. In this paper, three new species of Pseudopoda are described from East and Southeast Asia. Among them, one from China: P. fengtongzhaiensis Jäger & Liu, sp. nov. (♀); one from Laos: P. baimai Jäger & Liu, sp. nov. (♀); and one from Thailand: P. inthanonensis Jäger & Liu, sp. nov. (♀). Additionally, the female of P. kavanaughi Zhang, Jäger & Liu, 2023 is described for the first time. Photos of the habitus and genitalia, as well as a distribution map of all four species, are provided.

Abstract Multiple gene abnormalities are major drivers of tumorigenesis. NF-κB p65 overactivation and cGAS silencing are important triggers and genetic defects that accelerate tumorigenesis. However, the simultaneous correction of NF-κB p65 and cGAS abnormalities remains to be further explored. Here, we propose a novel Induced Dual-Target Rebalance (IDTR) strategy for simultaneously correcting defects in cGAS and NF-κB p65. By using our IDTR approach, we showed for the first time that oncolytic adenovirus H101 could reactivate silenced cGAS, while silencing GAU1 long noncoding RNA (lncRNA) inhibited NF-κB p65 overactivation, resulting in efficient in vitro and in vivo antitumor efficacy in colorectal tumors. Intriguingly, we further demonstrated that oncolytic adenoviruses reactivated cGAS by promoting H3K4 trimethylation of the cGAS promoter. In addition, silencing GAU1 using antisense oligonucleotides significantly reduced H3K27 acetylation at the NF-κB p65 promoter and inhibited NF-κB p65 transcription. Our study revealed an aberrant therapeutic mechanism underlying two tumor defects, cGAS and NF-κB p65, and provided an alternative IDTR approach based on oncolytic adenovirus and antisense oligonucleotides for efficient therapeutic efficacy in tumors.

Abstract Background Fractures involving the posterior acetabulum with its rich vascular and neural supply present challenges in trauma orthopedics. This study evaluates the effectiveness of 3D printing technology with the use of custom-made metal plates in the treatment of posterior wall and column acetabular fractures. Methods A retrospective analysis included 31 patients undergoing surgical fixation for posterior wall and column fractures of the acetabulum (16 in the 3D printing group, utilizing 3D printing for a 1:1 pelvic model and custom-made plates based on preoperative simulation; 15 in the traditional group, using conventional methods). Surgical and instrument operation times, intraoperative fluoroscopy frequency, intraoperative blood loss, fracture reduction quality, fracture healing time, preoperative and 12-month postoperative pain scores (Numeric Rating Scale, NRS), hip joint function at 6 and 12 months (Harris scores), and complications were compared. Results The surgical and instrument operation times were significantly shorter in the 3D printing group (p 0.05). However, at 12 months, hip joint function and pain scores were significantly better in the 3D printing group (p

Abiotic stress reduces plant yield and quality. WRKY transcription factors play key roles in abiotic stress responses in plants, but the molecular mechanisms by which WRKY transcription factors mediate responses to drought and osmotic stresses in apple (Malus × domestica Borkh.) remain unclear. Here, we functionally characterized the apple Group III WRKY gene MdWRKY115. qRT-PCR analysis showed that MdWRKY115 expression was up-regulated by drought and osmotic stresses. GUS activity analysis revealed that the promoter activity of MdWRKY115 was enhanced under osmotic stress. Subcellular localization and transactivation assays indicated that MdWRKY115 was localized to the nucleus and had a transcriptional activity domain at the N-terminal region. Transgenic analysis revealed that the overexpression of MdWRKY115 in Arabidopsis plants and in apple callus markedly enhanced their tolerance to drought and osmotic stresses. DNA affinity purification sequencing showed that MdWRKY115 binds to the promoter of the stress-related gene MdRD22. This binding was further verified by an electrophoretic mobility shift assay. Collectively, these findings suggest that MdWRKY115 is an important regulator of osmotic and drought stress tolerance in apple.

Abstract Rare-earth engineering is an effective way to introduce and tune magnetism in topological kagome materials, which have been acting as a fertile platform to investigate the quantum interactions between geometry, topology, spin, and correlation. Here, we report the synthesis, structure, and physical properties of titanium-based kagome metals RETi3Bi4 (RE = Yb, Pr, and Nd) with various magnetic states. They all crystallize in the orthogonal space group Fmmm (No. 69), featuring distorted titanium kagome lattices and rare-earth zig-zag chains. By changing the rare earth atoms in the zig-zag chains, the magnetism can be tuned from nonmagnetic YbTi3Bi4 to short-range ordered PrTi3Bi4 (T anomaly ~ 8.2 K), and finally to ferromagnetic NdTi3Bi4 (T c ~ 8.5 K). In-situ resistance measurements of NdTi3Bi4 under high pressure further reveal a tunable ferromagnetic ordering temperature. These results highlight RETi3Bi4 as a promising family of kagome metals to explore nontrivial band topology and exotic phases.

Abstract The chemokine CXCL8, also known as the neutrophil chemotactic factor, plays a crucial role in mediating inflammatory responses and managing cellular immune reactions during viral infections. Porcine reproductive and respiratory syndrome virus (PRRSV) primarily infects pulmonary alveolar macrophages (PAMs), leading to acute pulmonary infections. In this study, we explored a novel long non-coding RNA (lncRNA), termed lnc-CAST, situated within the Cxcl8 gene locus. This lncRNA was found to be highly expressed in porcine macrophages. We observed that both lnc-CAST and CXCL8 were significantly upregulated in PAMs following PRRSV infection, and after treatments with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Furthermore, we noticed a concurrent upregulation of lnc-CAST and CXCL8 expression in lungs of PRRSV-infected pigs. We then determined that lnc-CAST positively influenced CXCL8 expression in PAMs. Overexpression of lnc-CAST led to an increase in CXCL8 production, which in turn enhanced the migration of epithelial cells and the recruitment of neutrophils. Conversely, inhibiting lnc-CAST expression resulted in reduced CXCL8 production in PAMs, leading to decreased migration levels of epithelial cells and neutrophils. From a mechanistic perspective, we found that lnc-CAST, localized in the nucleus, facilitated the enrichment of histone H3K27ac in CXCL8 promoter region, thereby stimulating CXCL8 transcription in a cis-regulatory manner. In conclusion, our study underscores the pivotal critical role of lnc-CAST in regulating CXCL8 production, offering valuable insights into chemokine regulation and lung damage during PRRSV infection.

To enhance the overall performance of Mo–Cu alloy, Ti was added to Mo–Cu alloy to improve the bonding strength of Mo/Cu interface and generate solid solution strengthening effect. The outstanding performances of Mo–Cu–Ti alloys were achieved by infiltrating Cu–Ti alloy with different compositions into the Mo skeleton. Compared to the incoherent interface of Mo/Cu in Mo–Cu alloy, the addition of Ti transformed its interface to the coherent interface of Mo–Ti/Cu–Ti. All Mo–Cu–Ti alloy blocks had higher relative densities (97.4%∼98.5%) to guarantee the excellent comprehensive performances. What's more, the existences of Mo–Ti and Cu–Ti solid solutions assured the alloy possessed relatively high mechanical strength. The introduction of Ti purified the grain boundary by absorbing oxygen to generate TiO2 which hindered the growth of Mo–Ti grains. As increasing Ti amount from 0 wt% to 4.62 wt%, the Mo–Ti (or Mo) grain size reduced from 5 μm to 4.1 μm. Notably, Mo–Cu alloy block with the addition of 2.30 wt% Ti possessed the highest tensile strength of 562 MPa. Additionally, since the finer grain size of Mo–Ti alloy, this sample also owned the maximum micro-hardness and bending strength of 268 HV and 1730 MPa, respectively. Nevertheless, the presences of Cu–Ti solid solution and TiO2 also destroyed the electrical conductivities of the samples to some extent.

In response to the existing problems in the prediction accuracy, data collection, real-time monitoring, and consideration of factors leading to depression in the current mechanism for predicting depression among college students, this article used computer intelligent systems to study the prediction mechanism of depression among college students. This article conducted a survey on students at University A using a survey questionnaire to understand the main reasons that affect their tendency to develop depression. It processed and analyzed the data using the Beck Depression Scale and Statistical Product and Service Solution 21.0 (SPSS 21.0). Meanwhile, natural language processing techniques in computer intelligence systems can be utilized. This article combines emotional dictionaries and word frequency-inverse document frequency to construct a prediction mechanism model for depression tendencies among college students, improving the accuracy of predicting student depression tendencies. The experiment shows that the average accuracy of the depression tendency prediction mechanism model constructed based on Natural Language Processing technology after 50 experiments was 97.02%, which was 5.33% higher than the model constructed based on neural network calculations. Overall, research on the prediction mechanism of depression tendency among college students based on computer intelligence systems can provide more effective mental health support and intervention measures for schools, helping students improve their psychological state, academic achievement, and quality of life.

Abstract Background Postoperative hyper-inflammation is a frequent event in patients with acute Stanford type A aortic dissection (ATAAD) after surgical repair. This study's objective was to determine which inflammatory biomarkers could be used to make a better formula for identifying postoperative hyper-inflammation, and which risk factors were associated with hyper-inflammation. Methods A total of 405 patients were enrolled in this study from October 1, 2020 to April 1, 2023. Of these patients, 124 exhibited poor outcomes. In order to investigate the optimal cut-off values for poor outcomes, logistic and receiver operating characteristic analyses were performed on the following parameters on the first postoperative day: procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and systemic immune-inflammation index (SII). These cut-off points were used to separate the patients into hyper-inflammatory (n = 52) and control (n = 353) groups. Finally, the logistic were used to find the risk factors of hyper-inflammatory. Results PCT, CRP, IL-6, and SII were independent risk factors of poor outcomes in the multivariate logistic model. Cut-off points of these biomarkers were 2.18 ng/ml, 49.76 mg/L, 301.88 pg/ml, 2509.96 × 109/L respectively. These points were used to define postoperative hyper-inflammation (OR 2.97, 95% CI 1.35–6.53, P 180 min, and deep hypothermia circulatory arrest (DHCA) > 40 min were the independent risk factors for hyper-inflammation. Conclusions PCT > 2.18, CRP > 49.76, IL-6 > 301.88, and SII 180 min and DHCA > 40 min were separate risk factors for postoperative hyper-inflammation.

Abstract CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout breast cancer cells. Inhibition of PRMT5 blocks the G1-to-S transition in the cell cycle independent of RB, leading to growth arrest in RB1-knockout cells. Proteomics analysis uncovers fused in sarcoma (FUS) as a downstream effector of PRMT5. Inhibition of PRMT5 results in dissociation of FUS from RNA polymerase II, leading to hyperphosphorylation of serine 2 in RNA polymerase II, intron retention, and subsequent downregulation of proteins involved in DNA synthesis. Furthermore, treatment with the PRMT5 inhibitor pemrametostat and a selective ER degrader fulvestrant synergistically inhibits growth of ER+/RB-deficient cell-derived and patient-derived xenografts. These findings highlight dual ER and PRMT5 blockade as a potential therapeutic strategy to overcome resistance to CDK4/6i in ER+/RB-deficient breast cancer.

Yttria-stabilized zirconia (YSZ), which exhibits a tetragonal phase, finds widespread application in the realm of high-temperature solid electrolytes. In the context of this research endeavor, a concerted effort was undertaken to procure a stable and controlled tetragonal phase structure within 5 mol% yttria-stabilized zirconia (5 YSZ) by modulating the precipitation rate of YSZ sols in three distinct precipitation environments, namely acidic (AC), near to neutral (NE), and alkaline (AL) conditions. Through the characterization of 5 YSZ compounds synthesized in these various environments, encompassing an assessment of their elemental composition, phase structure, local structure, and microscale morphology, it was discerned that under acidic conditions, the product exhibited non-uniform elemental distribution, pronounced agglomeration, and an abundance of hydroxyl groups, all of which proved detrimental to the stability of the tetragonal phase, resulting in the presence of 40.63% monoclinic phase. Conversely, under alkaline conditions, substantial agglomeration and hydroxyl group presence were also noted, with 34.7% monoclinic phase in the product. In stark contrast, under the condition which is near to neutral, the product demonstrated uniform elemental distribution, excellent dispersion characteristics, and a virtual absence of hydroxyl groups. The tetragonal phase structure remained stable and homogeneous, with almost negligible monoclinic phase content. Subsequent ceramic processing resulted in the highest attainable density (99.7%), coupled with the highest ionic conductivity at 850 °C (35.2 mS/cm). This study underscores that pH control during coprecipitation reactions stands as a robust and effective methodology for achieving a stable tetragonal phase structure.

Abstract Background Senecavirus A (SVA) causes an emerging vesicular disease (VD) with clinical symptoms indistinguishable from other vesicular diseases, including vesicular stomatitis (VS), foot-and-mouth disease (FMD), and swine vesicular disease (SVD). Currently, SVA outbreaks have been reported in Canada, the U.S.A, Brazil, Thailand, Vietnam, Colombia, and China. Based on the experience of prevention and control of FMDV, vaccines are the best means to prevent SVA transmission. Results After preparing an SVA inactivated vaccine (CH-GX-01-2019), we evaluated the immunogenicity of the SVA inactivated vaccine mixed with Imject® Alum (SVA + AL) or Montanide ISA 201 (SVA + 201) adjuvant in mice, as well as the immunogenicity of the SVA inactivated vaccine combined with Montanide ISA 201 adjuvant in post-weaned pigs. The results of the mouse experiment showed that the immune effects in the SVA + 201 group were superior to that in the SVA + AL group. Results from pigs immunized with SVA inactivated vaccine combined with Montanide ISA 201 showed that the immune effects were largely consistent between the SVA-H group (200 µg) and SVA-L group (50 µg); the viral load in tissues and blood was significantly reduced and no clinical symptoms occurred in the vaccinated pigs. Conclusions Montanide ISA 201 is a better adjuvant choice than the Imject® Alum adjuvant in the SVA inactivated vaccine preparation, and the CH-GX-01-2019 SVA inactivated vaccine can provide effective protection for pigs.

Renal fibrosis is the major pathological changes of Chronic kidney disease (CKD). Piezo1, a mechanical sensitive ion channel, is implicated in organ fibrosis. However, the precise role of Piezo1 in CKD fibrosis is unknown. The aims of this study were to identify that the role of Piezo1 in CKD fibrosis and its potential involvement of mitochondrial dysfunction. We performed the study with the Piezo1 agonist Yoda1, Bax inhibitor BAI1, Piezo1 inhibitor GsMTx4 and detected the injury, fibrosis, apoptosis markers and mitochondrial dysfunction. The results showed that the levels of apoptosis, mitochondrial dysfunction, injury and fibrosis increased in TCMK-1 cells after treatment with Yoda1. However, these changes that induced by Yoda1 were relieved by BAI1. Similarly, inhibition Piezo1 with GsMTx4 also partly relieved the renal injury, renal fibrosis, apoptosis and mitochondrial dysfunction in vivo and vitro. In conclusion, we found Piezo1 promoted the initiation and development of renal fibrosis and inhibiting Piezo1 improved the fibrosis.

Accurate and efficient prediction of concrete crack propagation path facilitates timely maintenance. To avoid errors arising from assumptions in physical models and parameter measurements, a data-driven prediction method for concrete crack propagation path is proposed. The spatio-temporal prediction approach is presented by unifying the conditional Generative Adversarial Network and Long Short-Term Memory Network (UcGLS-Net). The UcGLS-Net has the advantage of enabling temporal (by Long Short-Term Memory Network, LSTM) and spatial information (by the conditional Generative Adversarial Network, cGAN) in the concrete crack propagation process to be treated simultaneously and distinctly thus improving prediction accuracy. Notably, results demonstrate that UcGLS-Net still works in crack propagation path prediction even with unknown aggregate distribution. Moreover, the effects of historical input quantity and prediction intervals on prediction accuracy of the UcGLS-Net are studied and the network framework is optimized. Due to high efficiency, this study provides a new adaptable and real-time prediction method for concrete crack propagation path, offering support for the design, damage prediction, assessment, and maintenance of concrete structures.

The bond between reinforced bars and concrete has a significant impact on reinforced concrete structures. Incorporating steel fibers in concrete not only enhances the performance of the concrete but also influences the bond strength of embedded reinforcing bars. In this paper, experiments have been carried out to investigate the influences of different bar diameters, concrete cover and embedment lengths on bond-slip responses between reinforcing bars and steel fiber reinforced concrete (SFRC). Furthermore, pull-out tests with normal concrete were also executed as a comparative group. The bond-slip results of specimens were collected. The impact of embedment length, reinforcing bar diameter, and the existence of steel fibers on the bond behavior of reinforcing bars was comprehensively analyzed. Meanwhile, the results indicate that variations in the ratio of concrete cover to reinforcing bar diameter lead to different effects on the bond behavior of SFRC compared with normal concrete. Different failure modes of specimens were exhibited and discussed. Additionally, a mathematical model for bond strength of bars in SFRC was proposed based on the correction of the bond strength model with normal concrete, which shows good agreement with experimental results.

The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.