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Abstract Background Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes. Methods The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC. Results In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3β/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues. Conclusions Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.

Abstract Spatial omics technologies decipher functional components of complex organs at cellular and subcellular resolutions. We introduce Spatial Graph Fourier Transform (SpaGFT) and apply graph signal processing to a wide range of spatial omics profiling platforms to generate their interpretable representations. This representation supports spatially variable gene identification and improves gene expression imputation, outperforming existing tools in analyzing human and mouse spatial transcriptomics data. SpaGFT can identify immunological regions for B cell maturation in human lymph nodes Visium data and characterize variations in secondary follicles using in-house human tonsil CODEX data. Furthermore, it can be integrated seamlessly into other machine learning frameworks, enhancing accuracy in spatial domain identification, cell type annotation, and subcellular feature inference by up to 40%. Notably, SpaGFT detects rare subcellular organelles, such as Cajal bodies and Set1/COMPASS complexes, in high-resolution spatial proteomics data. This approach provides an explainable graph representation method for exploring tissue biology and function.

The aim of this paper is to establish some fixed point results for enriched Kannan-type mappings in convex metric spaces. We first give an affirmative answer to a recent Berinde and Păcurar's question (Remark 2.3) [J. Comput. Appl. Math., 386 (2021), 113217]. Furthermore, we establish the existence and uniqueness of fixed points for Suzuki-enriched Kannan-type mappings in the setting of convex metric spaces. Finally, we present an application to approximate the solution of the Volterra integral equations to support our results.

Abstract Objective Bladder cancer(BCa) was a disease that seriously affects patients’ quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. Methods We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. Results The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. Conclusion P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

Abstract The nonconventional yeast Kluyveromyces marxianus has potential for industrial production, but the lack of advanced synthetic biology tools for precise engineering hinders its rapid development. Here, we introduce a CRISPR-Cas9-mediated multilocus integration method for assembling multiple exogenous genes. Using SlugCas9-HF, a high-fidelity Cas9 nuclease, we enhance gene editing precision. Specific genomic loci predisposed to efficient integration and expression of heterologous genes are identified and combined with a set of paired CRISPR-Cas9 expression plasmids and donor plasmids to establish a CRISPR-based biosynthesis toolkit. This toolkit enables genome integration of large gene modules over 12 kb and achieves simultaneous quadruple-locus integration in a single step with 20% efficiency. As a proof-of-concept, we apply the toolkit to screen for gene combinations that promote heme production, revealing the importance of HEM4Km and HEM12Sc. This CRISPR-based toolkit simplifies the reconstruction of complex pathways in K. marxianus, broadening its application in synthetic biology.

Abstract Background The 2018/2023 ESC/ESH Guidelines underlined a gap how baseline cardiovascular disease (CVD) risk predicted blood pressure (BP) lowering benefits. Further, 2017 ACC/AHA Guideline and 2021 WHO Guideline recommended implementation studies about intensive BP control. Now, to bridge these guideline gaps, we conducted a post hoc analysis to validate whether the baseline CVD risk influences the effectiveness of the intensive BP control strategy, which was designed by China Rural Hypertension Control Project (CRHCP). Methods This is a post hoc analysis of CRHCP, among which participants were enrolled except those having CVD history, over 80 years old, or missing data. Subjects were stratified into quartiles by baseline estimated CVD risk and then grouped into intervention and usual care group according to original assignment in CRHCP. Participants in the intervention group received an integrated, multi-faceted treatment strategy, executed by trained non-physician community health-care providers, aiming to achieve a BP target of

Abstract In recombinant protein-producing yeast strains, cells experience high production-related stresses similar to high temperatures. It is possible to increase recombinant protein production by enhancing thermotolerance, but few studies have focused on this topic. Here we aim to identify cellular regulators that can simultaneously activate thermotolerance and high yield of recombinant protein. Through screening at 46 °C, a heat-resistant Kluyveromyces marxianus (K. marxianus) strain FDHY23 is isolated. It also exhibits enhanced recombinant protein productivity at both 30 °C and high temperatures. The CYR1N1546K mutation is identified as responsible for FDHY23’s improved phenotype, characterized by weakened adenylate cyclase activity and reduced cAMP production. Introducing this mutation into the wild-type strain greatly enhances both thermotolerance and recombinant protein yields. RNA-seq analysis reveals that under high temperature and recombinant protein production conditions, CYR1 mutation-induced reduction in cAMP levels can stimulate cells to improve its energy supply system and optimize material synthesis, meanwhile enhance stress resistance, based on the altered cAMP signaling cascades. Our study provides CYR1 mutation as a novel target to overcome the bottleneck in achieving high production of recombinant proteins under high temperature conditions, and also offers a convenient approach for high-throughput screening of recombinant proteins with high yields.

Objective To explore the role of indole-3-propionic acid (IPA) in the pathogenesis of metabolic associated fatty liver disease (MAFLD) induced by high-fat diet (HFD) in order to reveal the role and related mechanism of adipose tissue metabolism in the process. Methods A mouse model of MAFLD was induced by HFD. Male C57BL/6J mice (6~7 weeks old) were randomly divided into control group (CON), HFD group, and HFD+IPA intervention group (HFD+IPA). The CON group was fed with control diet, and the HFD group and HFD+IPA group were fed with 60% of high-fat diet. The experiment period was 12 weeks, and IPA was administered at 20 mg/(kg·d) for 6 weeks starting from the 7th week. The body weight and food intake of each group were monitored weekly. After the intervention, the body composition of mice was detected by animal body composition analyzer. After the mice were euthanized, the morphological and structural changes in the liver and adipose tissues were observed by HE staining, the indicators relevant to lipid metabolism in the serum, liver and adipose tissues were detected by automatic blood biochemical analyzer and biochemical kits, and the mRNA expression changes of lipid metabolism and inflammation related genes were detected by qRT-PCR. Results Compared with the CON group, the HFD group had significantly increased body weight and body fat percentage, obvious lipid deposition in the liver, obviously elevated serum alanine aminotransferase, aspartate aminotransferase, liver triglyceride and total cholesterol levels (P < 0.05), and raised mRNA levels of liver fatty acid transporter CD36 (P < 0.05), while IPA intervention significantly reversed the above changes (P < 0.05). IPA intervention significantly inhibited the HFD-induced enlargement of visceral and brown fat cells, reduced the content of visceral adipose tissue (VAT) and serum level of free fatty acids (P < 0.05), and increased the mRNA expression levels of VAT lipolysis (HSL, CGI58), browning genes (Cidea, ND5, UCP1, Prdm16) (P < 0.05), as well as those of brown adipose tissue (BAT) lipolysis (HSL, ATGL) and fatty acid beta oxidation (Cpt1a, PPARα) genes (P < 0.05). Meanwhile, the mRNA levels of TNF-α, IL-1β, CXCL1 and CCL2 in VAT and BAT were decreased after IPA intervention (P < 0.05). Conclusion IPA can improve the occurrence of MAFLD induced by HFD, and its mechanism may be closely associated with its regulation of BAT and VAT morphology, and the mRNA expression of metabolic function and inflammation related genes.

Background Cervical cancer (CC) is a neoplasia with a high heterogeneity. We aimed to explore the characteristics of tumor microenvironment (TME) for CC treatment. Methods HPV positive (+) and negative (−) samples from cervical cancer (CC) patients were sourced from the Gene Expression Omnibus (GEO) database. The single-cell RNA sequencing (scRNA-seq) data were processed and annotated for cell types utilizing the Seurat package. Following this, the expression levels and biological roles of the marker genes were analyzed applying real-time PCR (RT-PCR) and transwell assays. Furthermore, the enrichment of genes with significantly differential expressions and copy number variations was assessed by the ClusterProlifer and inferCNV software packages. Results Seven main cell clusters were classified based on a total of 12,431 cells. The HPV− CC samples exhibited a higher immune cell infiltration level, while epithelial cells and myofibroblasts had higher proportion in the HPV+ CC samples with extensive heterogeneity. Immune pathways including antigen treatment and presentation, immunoglobulin production and T cell mediated immunity were significantly activated in the HPV− CC group with lower cell cycle and proliferation activity. However, the anti-tumor immunity of these cells was inhibited in HPV+ CC group with higher cell proliferation activity. Moreover, the amplification and loss of CNVs also supported that these cells in HPV− CC samples were prone to anti-tumor activation. Further cell validation results showed that except GZMA, the levels of APOC1, CEACAM6, FOXP3, SFRP4 and TFF3 were all higher in CC cells Hela, and that silencing TFF3 could inhibit the migration and invasion of CC cells in-vitro. Conclusion This study highlighted the critical role of HPV infection in CC progression, providing a novel molecular basis for optimizing the current preventive screening and personalized treatment for the cancer.

We proposed a non-contact photoacoustic (PA) detection method using spectral domain optical coherence tomography (SDOCT). Two interference spectrums (A-lines) were acquired before and after the PA excitation with SDOCT. PA signal propagated within the sample causing the vibration. The vibration inner the sample introduced phase change between the acquired two A-lines. Thus, the PA signal can be detected by evaluating the difference in phase between the two A-lines. Based on the method, an OCT-PAM dual-mode imaging system was constructed. In the system, SDOCT served as the detection unit for PAM. Thus, the combination of the two imaging modalities was simplified. Another advantage of the system is that it realizes non-contact all-optic detection, which is attractive for biomedical imaging. Using the system, we imaged phantoms of carbon fibers, asparagus leaves and human hairs. Furthermore, the cortical vasculature of rat was imaged in vivo and the flow status was evaluated quantitatively.

In the study of cavitation in room-temperature fluids, the heat transfer between gas and liquid in bubble oscillation is usually assumed to be an adiabatic process for simplification. However, this heat transfer and thermodynamic mechanism is not yet understood in cryogenic fluids, especially under small amplitude oscillation conditions excited by ultrasonic field. This article studies bubble thermodynamic model under an external ultrasonic field based on the heat transfer equation for cryogenic fluids. The temperature changes inside bubbles are calculated, and the heat transfer mechanism is briefly analyzed. The results indicate that the heat transfer mechanism of bubbles depends on the relationship between ultrasonic frequency and bubble resonance frequency. By analyzing two special cases of dual-bubble and high-pressure environment, it is believed that heat transfer can be approximated as an adiabatic process under high-pressure conditions with ultrasonic frequency far from the resonance frequency. This conclusion can provide a theoretical basis for subsequent accurate calculation of heat-transfer polytropic coefficient, or void faction measurement in cryogenic two-phase flow.

The forming technology of surface micropattern structure was widely used in practical manufacturing as a means to texture the surface of materials and to promote advanced and functional materials. The main methods of surface micropattern forming include hot embossing, chemical etching, electrical discharge machining(EDM), photolithography and 3D printing depending on the application areas of materials. The different surface micropattern structure forming techniques and the basic principles of preparing surface texturise functional materials were reviewed, and their practical applications in photovoltaics, electronic information, intelligent manufacturing, ultra-precision manufacturing and other fields were listed. The characteristics and scope of application of different surface micropattern structure forming technologies are summarized, and the key problems faced in realizing the surface texturisation and functionalization of materials are put forward, which provides certain reference for the micromachining technology of surface micropattern structures.

Abstract Kluyveromyces marxianus is a food‐safe yeast with great potential for producing heterologous proteins. Improving the yield in K. marxianus remains a challenge and incorporating large‐scale functional modules poses a technical obstacle in engineering. To address these issues, linear and circular yeast artificial chromosomes of K. marxianus (KmYACs) were constructed and loaded with disulfide bond formation modules from Pichia pastoris or K. marxianus. These modules contained up to seven genes with a maximum size of 15 kb. KmYACs carried telomeres either from K. marxianus or Tetrahymena. KmYACs were transferred successfully into K. marxianus and stably propagated without affecting the normal growth of the host, regardless of the type of telomeres and configurations of KmYACs. KmYACs increased the overall expression levels of disulfide bond formation genes and significantly enhanced the yield of various heterologous proteins. In high‐density fermentation, the use of KmYACs resulted in a glucoamylase yield of 16.8 g/l, the highest reported level to date in K. marxianus. Transcriptomic and metabolomic analysis of cells containing KmYACs suggested increased flavin adenine dinucleotide biosynthesis, enhanced flux entering the tricarboxylic acid cycle, and a preferred demand for lysine and arginine as features of cells overexpressing heterologous proteins. Consistently, supplementing lysine or arginine further improved the yield. Therefore, KmYAC provides a powerful platform for manipulating large modules with enormous potential for industrial applications and fundamental research. Transferring the disulfide bond formation module via YACs proves to be an efficient strategy for improving the yield of heterologous proteins, and this strategy may be applied to optimize other microbial cell factories.

The purpose of this paper is to present a study of $ \alpha $-$ \eta $-type generalized $ F $-proximal contraction mappings in the framework of modular metric spaces and to prove some best proximity point theorems for these types of mappings. Some examples are given to show the validity of our results. We also apply our results to establish the existence of solutions for a certain type of non-linear integral equation.

In this paper, we investigated several new fixed points theorems for multivalued mappings in the framework $ b $-metric spaces. We first generalized $ S $-iterative schemes for multivalued mappings to above spaces by means of a convex structure and then we developed the existence of fixed points and approximate endpoints of the multivalued contraction mappings using iteration techniques. Furthermore, we introduced the modified $ S $-iteration process for approximating a common endpoint of a multivalued $ \alpha_{s} $-nonexpansive mapping and a multivalued mapping satisfying conditon $ (E^{'}) $. We also showed that this new iteration process converges faster than the $ S $-iteration process in the sense of Berinde. Some convergence results for this iterative procedure to a common endpoint under some certain additional hypotheses were proved. As an application, we applied the $ S $-iteration process in finding the solution to a class of nonlinear quadratic integral equations.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

IntroductionThe Xinjiang Mongolians, located along the Silk Road, migrated westward from Northeast Asia in the 13th and 14th centuries. Despite its significance, genetic studies on Xinjiang Mongolians have been limited compared to other Mongolian populations.MethodsIn this study, we analyzed the non-recombining region of the Y-chromosome in 165 Xinjiang Mongolian males using 108 biallelic markers and 44 STRs.Results and discussionOur study identified prevalent haplogroups C2a1a3-F1918 (10%), C2a1a2-M48 (8%), N1a1a-M178 (5%), and R1a1a-M17 (10%) in the Xinjiang Mongolians. Additionally, our study suggested a genetic affinity between Xinjiang Mongolians and Inner Mongolia Mongolian populations, as well as other ethnic groups from northwest China, based on the PCA analysis. The Network analysis revealed distinct branching expansion patterns in haplogroups C2a1a3a-F3796, C2a1a2-M48, and N1a1a-M178, with estimated timeframes aligning with Genghis Khan's invasion of Xinjiang in the Yuan Dynasty. Notably, our analysis of the R1a1a-M17 Network highlighted the role of Xinjiang Mongolians in the expansion of Turkic-speaking populations in Xinjiang and surrounding regions. The integration of ancient DNA data suggested that the high frequency haplogroups C2a1a3a-F3796, C2a1a2-M48, and N1a1a-M178 could be traced back to their origin in Northeast Asia. Furthermore, the estimated TMRCA of haplogroup R1a1a-M17 implied cultural and genetic influences from Turkic populations during the Qagatay Khanate period. Overall, our study provided a genetic explanation for the ethnic origin of Xinjiang Mongolians, highlighting their migration from Northeast Asia and subsequent assimilation with the local populations in Xinjiang.

Abstract Highly multiplexed protein imaging is emerging as a potent technique for analyzing protein distribution within cells and tissues in their native context. However, existing cell annotation methods utilizing high-plex spatial proteomics data are resource intensive and necessitate iterative expert input, thereby constraining their scalability and practicality for extensive datasets. We introduce MAPS (Machine learning for Analysis of Proteomics in Spatial biology), a machine learning approach facilitating rapid and precise cell type identification with human-level accuracy from spatial proteomics data. Validated on multiple in-house and publicly available MIBI and CODEX datasets, MAPS outperforms current annotation techniques in terms of speed and accuracy, achieving pathologist-level precision even for typically challenging cell types, including tumor cells of immune origin. By democratizing rapidly deployable and scalable machine learning annotation, MAPS holds significant potential to expedite advances in tissue biology and disease comprehension.

Abstract Background The 5´ untranslated region (5´ UTR) plays a key role in regulating translation efficiency and mRNA stability, making it a favored target in genetic engineering and synthetic biology. A common feature found in the 5´ UTR is the poly-adenine (poly(A)) tract. However, the effect of 5´ UTR poly(A) on protein production remains controversial. Machine-learning models are powerful tools for explaining the complex contributions of features, but models incorporating features of 5´ UTR poly(A) are currently lacking. Thus, our goal is to construct such a model, using natural 5´ UTRs from Kluyveromyces marxianus, a promising cell factory for producing heterologous proteins. Results We constructed a mini-library consisting of 207 5´ UTRs harboring poly(A) and 34 5´ UTRs without poly(A) from K. marxianus. The effects of each 5´ UTR on the production of a GFP reporter were evaluated individually in vivo, and the resulting protein abundance spanned an approximately 450-fold range throughout. The data were used to train a multi-layer perceptron neural network (MLP-NN) model that incorporated the length and position of poly(A) as features. The model exhibited good performance in predicting protein abundance (average R2 = 0.7290). The model suggests that the length of poly(A) is negatively correlated with protein production, whereas poly(A) located between 10 and 30 nt upstream of the start codon (AUG) exhibits a weak positive effect on protein abundance. Using the model as guidance, the deletion or reduction of poly(A) upstream of 30 nt preceding AUG tended to improve the production of GFP and a feruloyl esterase. Deletions of poly(A) showed inconsistent effects on mRNA levels, suggesting that poly(A) represses protein production either with or without reducing mRNA levels. Conclusion The effects of poly(A) on protein production depend on its length and position. Integrating poly(A) features into machine-learning models improves simulation accuracy. Deleting or reducing poly(A) upstream of 30 nt preceding AUG tends to enhance protein production. This optimization strategy can be applied to enhance the yield of K. marxianus and other microbial cell factories.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Mobile Edge Computing (MEC)-based computation offloading is a promising application paradigm for serving large numbers of users with various delay and energy requirements. In this paper, we propose a flexible MEC-based requirement-adaptive partial offloading model to accommodate each user's specific preference regarding delay and energy consumption. To address the dimensional differences between time and energy, we introduce two normalized parameters and then derive the computational overhead of processing tasks. Different from existing works, this paper considers practical variations in the user request patterns, and exploits a flexible partial offloading mode to minimize computation overheads subject to tolerable delay, task workload and power constraints. Since the resulting problem is non-convex, we decouple it into two convex subproblems and present an iterative algorithm to obtain a feasible offloading solution. Numerical experiments show that our proposed scheme achieves a significant improvement in computation overheads compared with existing schemes.

Abstract The coronavirus disease 2019 (COVID‐19) has developed into a global health crisis. Pulmonary fibrosis, as one of the complications of SARS‐CoV‐2 infection, deserves attention. As COVID‐19 is a new clinical entity that is constantly evolving, and many aspects of disease are remain unknown. The datasets of COVID‐19 and idiopathic pulmonary fibrosis were obtained from the Gene Expression Omnibus. The hub genes were screened out using the Random Forest (RF) algorithm depending on the severity of patients with COVID‐19. A risk prediction model was developed to assess the prognosis of patients infected with SARS‐CoV‐2, which was evaluated by another dataset. Six genes (named NELL2, GPR183, S100A8, ALPL, CD177, and IL1R2) may be associated with the development of PF in patients with severe SARS‐CoV‐2 infection. S100A8 is thought to be an important target gene that is closely associated with COVID‐19 and pulmonary fibrosis. Construction of a neural network model was successfully predicted the prognosis of patients with COVID‐19. With the increasing availability of COVID‐19 datasets, bioinformatic methods can provide possible predictive targets for the diagnosis, treatment, and prognosis of the disease and show intervention directions for the development of clinical drugs and vaccines.

AIM: To study retinal microvascular and microstructural alterations in meibomian gland dysfunction (MGD) in severely obese population using optical coherence tomography angiography (OCTA). METHODS: Twelve MGD patients with severely obese population (PAT group; 24 eyes) and 12 healthy controls (HC group; 24 eyes) were recruited. OCTA images were segmented into five [superior (S), nasal (N), inferior (I), temporal (T), and central foveal (C)] or nine [inner superior (IS), outer superior (OS), inner nasal (IN), outer nasal (ON), inner inferior (II), outer inferior (OI), inner temporal (IT), outer temporal (OT), and C] subregions. The superficial vessel density (SVD), retinal thickness (RT), foveal avascular zone (FAZ) parameters, and retinal volume were measured. RESULTS: Visual acuity was significantly different between two groups (0.8±0.17 in PAT group vs 0.2±0.06 in HC group). SVD was significantly lower in PATs in N, T, OS, IN, OT, and ON. The area under the receiver operating characteristic curve (AUC) for T was 0.961 [95% confidence interval (CI): 0.908 to 1.000], for OS was 0.962 (95%CI: 0.915 to 1.000). RT was significantly lower in PATs in IS, OS, OI, OT, ON, IT, IN, and II. AUC for OT was 0.935 (95%CI: 0.870 to 0.999), for IS was 0.915 (95% CI: 0.838 to 0.992). Angiography results showed significantly lower area and perimeter of FAZ, SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group. CONCLUSION: Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures. These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.

Objective To study the buccolingual inclination of posterior premolars and molars and the curve of Wilson in patients with different sagittal skeletal patterns, to explore the compensation mechanism of horizontal inclination of posterior teeth in patients with different sagittal skeletal patterns and to provide a reference for the control of posterior tooth inclination in the treatment of bone malocclusion. Methods This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Ninety CBCT scans of adults and ninety scans of adolescents before orthodontic treatment were evaluated in this cross-sectional study. There were 30 skeletal Class I, Class Ⅱ, and Class Ⅲ patients in the adult group and adolescent group. The inclination angles of posterior teeth and the curve of Wilson of first and second molars were measured, and data were analyzed between adolescents and adults with different sagittal skeletal patterns. Results Compared with skeletal Class Ⅰ adult patients, the upper posterior molar inclination of skeletal Class Ⅱ patients was significantly lower, and the lower posterior molar inclination was significantly higher. Compared with skeletal ClassⅠ adult patients, the upper posterior molar inclination of skeletal Class Ⅲ adult patients was higher, and the lower posterior molar inclination was significantly lower. The Wilson curve of the second molar in skeletal Class Ⅱ adult patients was significantly higher than that in the other groups. Compared with skeletal ClassⅠ adolescent patients, skeletal Class Ⅲ adolescent patients had a significantly higher upper posterior molar inclination; however, no difference was found between the inclination of the posterior teeth between skeletal Class Ⅰ, Class Ⅱ and Class Ⅲ adolescent patients. Comparing adolescent and adult samples, in skeletal Class Ⅱ patients, adults showed more lingual inclination than adolescents in the upper posterior teeth and less lingual inclination in the lower posterior teeth except for the mandibular first molar. Comparing adolescent and adult samples, in skeletal Class Ⅲ patients, adults showed more lingual inclination than adolescents in the lower posterior teeth except for the mandibular second molars and showed no difference in the upper posterior teeth. Conclusions The inclination of the posterior teeth and the curve of Wilson show significant differences between the three sagittal skeletal patterns. Compared with those of skeletal Class Ⅰ patients, the posterior teeth of skeletal Class Ⅱ patients show more lingual inclination in the upper arch and less lingual inclination in the lower arch. Meanwhile, posterior teeth of skeletal Class Ⅲ patients show more lingual inclination in the lower arch and maintain the inclination in the upper arch.

The use of Generally Recognized as Safe (GRAS)-grade microbial cell factories to produce recombinant protein-based nutritional products is a promising trend in developing food and health supplements. In this study, GRAS-grade Kluyveromyces marxianus was employed to express recombinant human heavy-chain ferritin (rhFTH), achieving a yield of 11 g/L in a 5 L fermenter, marking the highest yield reported for ferritin nanoparticle proteins to our knowledge. The rhFTH formed 12 nm spherical nanocages capable of ferroxidase activity, which involves converting Fe2+ to Fe3+ for storage. The rhFTH-containing yeast cell lysates promoted cytokine secretion (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1β (IL-1β)) and enhanced locomotion, pharyngeal pumping frequency, egg-laying capacity, and lifespan under heat and oxidative stress in the RAW264.7 mouse cell line and the C. elegans model, respectively, whereas yeast cell lysate alone had no such effects. These findings suggest that rhFTH boosts immunity, holding promise for developing ferritin-based food and nutritional products and suggesting its adjuvant potential for clinical applications of ferritin-based nanomedicine. The high-yield production of ferritin nanoparticles in K. marxianus offers a valuable source of ferritin for the development of ferritin-based products.

Mechanical ventilation is an important means of environmental control in multitier laying hen cages. The mainstream ventilation mode currently in use, negative-pressure ventilation (NPV), has the drawbacks of a large temperature difference before and after adjustment and uneven air velocity distribution. To solve these problems, this study designed and analyzed a combined positive and negative-pressure ventilation system for laying hen cages. According to the principle of the conservation of mass to increase the inlet flow in the negative-pressure ventilation system on the basis of the addition of the pressure-wind body-built positive-and-negative-pressure-combined ventilation (PNCV) system, further, computational fluid dynamics (CFD) simulation was performed to analyze the distribution of environmental parameters in the chicken cage zone (CZ) with inlet angles of positive-pressure fans set at 45°, 90°, and 30°. Simulation results showed that the PNCV system increased the average air velocity in the CZ from 0.94 m/s to 1.04 m/s, 1.28 m/s, and 0.99 m/s by actively blowing air into the cage. The maximum temperature difference in the CZ with the PNCV system was 2.91 °C, 1.80 °C, and 3.78 °C, which were all lower than 4.46 °C, the maximum temperature difference in the CZ with the NPV system. Moreover, the relative humidity remained below 80% for the PNCV system and between 80% and 85% for the NPV system. Compared with the NPV system, the PNCV system increased the vertical airflow movement, causing significant cooling and dehumidifying effects. Hence, the proposed system provides an effective new ventilation mode for achieving efficient and accurate environmental control in laying hen cages.

Prostate cancer (PCa) is initially sensitive to androgen deprivation therapy (ADT) but ultimately develops resistance and progresses to castration-resistant prostate cancer (CRPC) with a poor prognosis. This study indicated that some PCa patients and mice were more sensitive to ADT and entered CRPC later, which was related to the gut microbiota, especially the enrichment of Akkermansia muciniphila (AKK). Untargeted metabolomics analysis found that serum inosine level was upregulated in the treatment-sensitive group and significantly correlated with AKK. Furthermore, we revealed that intestinal permeability and serum lipopolysaccharide (LPS) levels increased in treatment-resistant mice. LPS stimulated the upregulation of p-NF-κB p65 and AR in tumors. Supplementing AKK metabolite inosine could alleviate intestinal barrier damage and reduce serum LPS level, ultimately inhibiting castration resistance via the LPS/NF-κB/AR axis. Finally, we constructed a predictive model for CRPC combining gut microbiota and clinical information (AUC = 0.729). This study revealed the potential mechanism of gut microbiota on CRPC and provided potential therapeutic targets and prognostic indicators.

Head and neck squamous cell carcinoma (HNSCC) is a globally prevalent and lethal cancer form, whose precise mechanisms remain incompletely understood. Increasing evidence suggests that N6-methyladenosine (m6A) plays a crucial role in cancer progression. This study aimed to explore the biological function of m6A modification and vir-like m6A methyltransferase associated (VIRMA) in HNSCC. We conducted an analysis of VIRMA expression in HNSCC cells using The Cancer Genome Atlas (TCGA) database and employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting to assess its expression levels in HNSCC cell lines. Additionally, m6A levels in HNSCC cells were quantified, and the correlation between VIRMA expression levels and the clinical and pathological features of other genes was analyzed. Upon knocking down VIRMA levels, we assessed HNSCC cell proliferation, migration, and invasion and validated downstream genes using RT-qPCR and western blot. Our findings suggested that VIRMA, as an m6A-related regulator, may significantly influence HNSCC progression by regulating ubiquitin protein ligase E3 component N-recognin 5 (UBR5) through m6A modification. Therefore, VIRMA may serve as a prognostic biomarker.

Purpose/Objectives: We sought to create nomograms to predict individual risk of early mortality, which can identify patients who require interventions to prevent early death. Methods: We included patients in the National Cancer Database with non-metastatic squamous cell carcinoma of the head and neck who received radiation and systemic therapy between 2004 and 2017 in the definitive or adjuvant setting. Early mortality was defined as any death less than 90 days after starting radiation. Multivariable logistic regression was used to assess the relationship between covariates and early mortality. Nomograms to predict the risk of early death were created for both the definitive and adjuvant settings. Results: Among 84,563 patients in the definitive group and 18,514 patients in the adjuvant group, rates of early mortality were 3.5 % (95 % CI 3.4–3.7 %) and 2.2 %, (95 % CI 1.9–2.4 %), respectively. Patients above the age of 70 had an early mortality rate of 7.8 % (95 % CI 7.3–8.2 %) in the definitive group and 4.4 % (95 % CI 3.6–5.4 %) in the adjuvant group. In the multivariable analysis, age, comorbidity, T and N category, and tumor site were associated with early mortality in both cohorts (p

Abstract Soil microorganisms play vital roles in regulating multiple ecosystem functions. Recent studies have revealed that the rare microbial taxa (with extremely low relative abundances, which are still largely ignored) are also crucial in maintaining the health and biodiversity of the soil and may respond differently to environmental pressure. However, little is known about the soil community structures of abundant and rare taxa and their assembly processes in different soil layers on the Qinghai‐Tibet Plateau (QTP). The present study investigated the community structure and assembly processes of soil abundant and rare microbial taxa on the northeastern edge of the QTP. Soil microbial abundance was defined by abundant taxa, whereas rare taxa contributed to soil microbial diversity. The results of null model show that the stochastic process ruled the assembly processes of all sub‐communities. Dispersal limitation contributed more to the assembly of abundant microbial taxa in the different soil layers. In contrast, drift played a more critical role in the assembly processes of the rare microbial taxa. In addition, in contrast to previous studies, the abundant taxa played more important roles in co‐occurrence networks, most likely because of the heterogeneity of the soil, the sparsity of amplicon sequencing, the sampling strategy, and the limited samples in the present study. The results of this study improve our understanding of soil microbiome assemblies on the QTP and highlight the role of abundant taxa in sustaining the stability of microbial co‐occurrence networks in different soil layers.

ObjectiveTo assess the effect of B cell depletion therapy (BCDT) on circulating T follicular helper (cTfh) and circulating T helper 17 (cTh17) cells and its relation to clinical improvement in patients with myasthenia gravis (MG).Methods28 anti-AchR positive MG patients treated with ofatumumab and 28 healthy controls (HCs) were included. Frequencies of cTfh and cTh17 cells were monitored by flow cytometry at baseline and 4, and 12 weeks after the initial dose ofatumumab. Serum cytokines associated with cTfh and cTh17, including IL-6, IL-21, and IL-17, were also analyzed.ResultsThe frequency of cTfh and cTh17 significantly increased in MG patients compared with HCs. Additionally, elevated levels of both T-cell subsets correlated with MG severity. During the follow-up, cTfh and cTh17 return to normal after BCDT. Furthermore, the decrease in cTfh and cTh17 was associated with MG scores improvement over time. Notably, cTfh- and cTh17-related cytokines, including IL-6, IL-21, and IL-17, exhibited a marked decrease following ofatumumab therapy.ConclusionsAbnormal expansion of cTfh and cTh17 cells may be key features in the immunopathology of MG. Their levels returned to normal after BCDT, which was closely correlated with clinical amelioration. This result suggests that these two T-cell subsets may be targets for BCDT treatment of MG.

Abstract Multifunctional nanomedicines have been used in atherosclerosis theranostics. Herein, phosphatidylserine‐specific peptide CLIKKPF‐functionalized carbon‐dots nanozymes (pep‐CDs) are reported for specific and efficient noninvasive theranostic of atherosclerosis. Surprisingly, pep‐CDs are discovered to not only inherit the inherent properties of carbon dots (CDs), including deep‐red fluorescence emission, photoacoustic response, and superoxide dismutase‐like antioxidant, and anti‐inflammatory activities but also possess the ability to target recognition on foam cells and target localization on plaques due to the specific interaction of CLIKKPF with phosphatidylserine on the membrane outer surface of foam cells. Furthermore, the target localization effect of pep‐CDs vastly promotes the efficient accumulation of CDs in plaque, thus maximizing AS theranostic of CDs. Interestingly, pep‐CDs could be developed to image plaque for monitoring atherosclerosis pathological progression in real‐time resulting from the different content of foam cells. This work on the one hand proposes a simple and feasible strategy to construct theranostic nanoplatform employing only a single functional unit (i.e., multifunctional CDs) to simplify the fabrication procedure, on the other hand, highlights the advantages of the active target auxiliary mode for atherosclerosis theranostic applications.

Abstract Background The addition of coronary artery calcium score (CACS) to prediction models has been verified to improve performance. Machine learning (ML) algorithms become important medical tools in an era of precision medicine, However, combined utility by CACS and ML algorithms in hypertensive patients to forecast obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CCTA) is rare. Methods This retrospective study was composed of 1,273 individuals with hypertension and without a history of CAD, who underwent dual-source computed tomography evaluation. We applied five ML algorithms, coupled with clinical factors, imaging parameters, and CACS to construct predictive models. Moreover, 80% individuals were randomly taken as a training set on which 5-fold cross-validation was done and the remaining 20% were regarded as a validation set. Results 16.7% (212 out of 1,273) of hypertensive patients had obstructive CAD. Extreme Gradient Boosting (XGBoost) posted the biggest area under the receiver operator characteristic curve (AUC) of 0.83 in five ML algorithms. Continuous net reclassification improvement (NRI) was 0.55 (95% CI (0.39–0.71), p

Abstract Objective To describe a novel method of medial fixation of titanium mesh with a right‐angled screwdriver for orbital floor and maxillary reconstruction and to compare the reconstruction outcome of orbital floor reconstruction with modified and traditional methods. Methods The data of 23 patients who underwent maxillectomy and orbital floor defect reconstruction by individualized titanium mesh in Peking University School and Hospital of Stomatology between 2018 and 2021 were retrospectively reviewed. While eight patients received modified orbital floor reconstruction with titanium mesh and angled screwdriver (group A), 15 patients received traditional orbital floor reconstruction (group B). The contact area with buccal flap for titanium mesh in groups A and B was calculated. Titanium mesh deformation, fracture or exposure was recorded. Postoperative ophthalmic function and success of esthetic restoration were assessed. Results Mean follow‐up was for 15.7 months (range, 9–22 months). The contact area with buccal flap for the modified titanium mesh in group A (13.11 ± 1.41 cm2) was significantly less than that of the traditional titanium mesh in group B (21.83 ± 1.23 cm2; p .05). No specific complications were reported. Conclusion We propose a novel method of zygomatic medial fixation of titanium mesh with a right‐angled screwdriver for orbital floor and maxillary reconstruction, which has the potential to prevent the postoperative exposure of titanium mesh. Level of Evidence Level III (Retrospective comparative study).

Reef islands are composed of unconsolidated carbonate sediment from the reef that has been organized and deposited on an atoll and platform reef by ocean hydrodynamics. They are frequently found in remote mid-ocean locations within tropical and subtropical waters and are the sole source for habitable land of some island nations. It is anticipated that sea level rise and more frequent and intense storms resulting from global climate change will destabilize these low-lying reef islands, thus there is increasing concern about the persistence and habitability of these islands during future extreme wave events. The reef island morphodynamic response to the action of regular waves has not been reported in the literature. Therefore, this study performed laboratory experiments based on a horizontally one-dimensional reef island physical model in a wave flume. The temporal variation of the island profile under regular waves was measured to analyze the effects of island morphological factors (initial island height and width) and initial island location on its topographic evolution. The results showed that the reef island lost crest elevation and migrated and extended toward its lagoon side under the action of regular waves. Accretion also occurred on the lagoon side beach and random ripples appeared. The time required for the island to reach its equilibrium profile decreased with increasing of initial island height, initial island width, and initial island distance from reef edge. The island crest lowering due to scouring increased with increase of initial island height, but it decreased with increasing of initial island width and initial island distance from the reef edge. Among the three factors, initial island height had the greatest impact on the crest lowering. The island lagoonward migration decreased with increasing of both initial island height and initial island distance from reef edge, but it increased with the increase of initial island width. Among the three factors, initial island location was the most influential factor to lagoonward migration, but no island lagoonward migration was detected when the initial island distance D≥2 m. Regression analysis was used to obtain empirical formulae to predict the island crest lowering and island lagoonward migration, respectively. The outcomes of this study provide a habitability assessment for such low-lying island nations in the context of global climate change.

This study explored the variation of ileal endogenous amino acid (IEAA) losses and its influencing factors in chickens offered nitrogen-free diets (NFD) containing different ratios of amylose to amylopectin (AM/AP). A total of 252 broiler chickens at 28 d old were randomly allocated into 7 treatment groups for a 3-d trial. The dietary treatments included a basal diet (control), a NFD containing corn starch (CS), and 5 NFD with AM/AP ratios of 0.20, 0.40, 0.60, 0.80, and 1.00, respectively. As the AM/AP ratio increased, the IEAA losses of all AAs, starch digestibility and maltase activity linearly decreased (P

Let $ \mathfrak{R}_{l, k} = {\mathbb F}_{p^m}[u_1, u_2, \cdots, u_k]/ \langle u_{i}^{l} = u_{i}, u_iu_j = u_ju_i = 0 \rangle $, where $ p $ is a prime, $ l $ is a positive integer, $ (l-1)\mid(p-1) $ and $ 1\leq i, j\leq k $. First, we define a Gray map $ \phi_{l, k} $ from $ \mathfrak{R}_{l, k}^n $ to $ {\mathbb F}_{p^m}^{((l-1)k+1)n} $, and study its Gray image. Further, we study the algebraic structure of $ \sigma $-self-orthogonal and $ \sigma $-dual-containing constacyclic codes over $ \mathfrak{R}_{l, k} $, and give the necessary and sufficient conditions for $ \lambda $-constacyclic codes over $ \mathfrak{R}_{l, k} $ to satisfy $ \sigma $-self-orthogonal and $ \sigma $-dual-containing. Finally, we construct quantum codes from $ \sigma $-dual-containing constacyclic codes over $ \mathfrak{R}_{l, k} $ using the CSS construction or Hermitian construction and compare new codes our obtained better than the existing codes in some recent references.

Abstract The control of unmanned aerial vehicle quadrotor is challenging because of non‐linearities, coupling and disturbance. Here, a novel control method which includes reinforcement learning (RL) component and robust component is proposed. In this method, the RL component only relies on collected data instead of modelling to handle coupling and disturbance from aerodynamics and model. To ensure safety during training and improve training speed, the robust component is used to reduce the disturbance .The stability of the system with our controller is proven by Lyapunov method. The results of the simulation exhibit advanced performance of our controller.

This research compared how different levels of dietary crude protein (CP) and apparent metabolizable energy (AME) affect the growth performance, nitrogen utilization, serum parameters, protein synthesis, and amino acid (AA) metabolism in broilers aged 1 to 10 days. In a 4 × 3 factorial experimental design, the broilers were fed four levels of dietary CP (20%, 21%, 22%, and 23%) and three levels of dietary AME (2800 kcal/kg, 2900 kcal/kg, and 3000 kcal/kg). A total of 936 one-day-old male Arbor Acres broilers were randomly allocated to 12 treatments with 6 replications each. Growth performance, nitrogen utilization, serum parameter, gene expression of protein synthesis, and AA metabolism were evaluated at 10 d. The results revealed no interaction between dietary CP and AME levels on growth performance (p > 0.05). However, 22% and 23% CP enhanced body weight gain (BWG), the feed conversion ratio (FCR), total CP intake, and body protein deposition but had a detrimental effect on the protein efficiency ratio (PER) compared to 20% or 21% CP (p < 0.05). Broilers fed diets with 2800 kcal/kg AME showed increased feed intake (FI) and inferior PER (p < 0.05). Broilers fed diets with 3000 kcal/kg AME showed decreased muscle mRNA expression of mammalian target of the rapamycin (mTOR) and Atrogin-1 compared to those fed diets with 2800 kcal/kg and 2900 kcal/kg AME (p < 0.05). Increasing dietary CP level from 20% to 23% decreased muscle mTOR and increased S6K1 mRNA expression, respectively (p < 0.05). The muscle mRNA expression of Atrogin-1 was highest for broilers fed 23% CP diets (p < 0.05). The mRNA expression of betaine homocysteine methyltransferase (BHMT) and Liver alanine aminotransferase of the 22% and 23% CP groups were higher than those of 20% CP (p < 0.05). Significant interactions between dietary CP and AME levels were observed for muscle AMPK and liver lysine-ketoglutarate reductase (LKR) and branched-chain alpha-keto acid dehydrogenase (BCKDH) mRNA expression (p < 0.05). Dietary AME level had no effect on muscle AMPK mRNA expression for broilers fed 21% and 22% CP diets (p > 0.05), whereas increasing dietary AME levels decreased AMPK mRNA expression for broilers fed 23% CP diets (p < 0.05). The mRNA expression of LKR and BCKDH was highest for broilers fed the diet with 2800 kcal/kg AME and 22% CP, while it was lowest for broilers fed the diet with 3000 kcal/kg AME and 20% CP. The findings suggest that inadequate energy density hindered AA utilization for protein synthesis, leading to increased AA catabolism for broilers aged 1 to 10 days, and a dietary CP level of 22% and an AME level of 2900 to 3000 kcal/kg may be recommended based on performance and dietary protein utilization.

Current challenges in collecting and analyzing subway vibration data include the absence of standardized data collection methods, limitations in data analysis techniques, and an unclear understanding of the effects of geological conditions on vibrations. This study investigated vertical vibrations of tunnel walls and the ground above tunnels under different geological conditions of soft soil and rock strata at horizontal distances of 0, 15 m, and 30 m from the tunnel center line during train passages. The collected data underwent Fourier transformation and 1/3 octave processing to extract spectral characteristics and analyze transmission losses across different frequency bands. Our findings revealed two vibration peaks in the transmission process for both soft soil and rock formation geology. Specifically, high-frequency vibrations in soft soil experienced greater attenuation when transmitted from the tunnel wall to the ground at 0 m, while low-frequency vibrations in rock formations showed greater attenuation. We also observed a vibration amplification phenomenon at 15 m under soft soil geology conditions. Although low-frequency vibrations below 12.5 Hz showed slight attenuation within a 30 m test distance under both geological conditions, vibrations above 40 Hz experienced significant attenuation. These results offer valuable insights for reducing vibrations in subway superstructures and planning subway lines under diverse geological conditions. Furthermore, this study serves not only as a basis for mitigating vibrations in metro spans and designing metro lines in various geological contexts but also establishes a scientific foundation for future research.

Abstract Gastric cancer is a deadly disease and gastric polyps are at high risk of becoming cancerous. Therefore, the timely detection of gastric polyp is of great importance which can reduce the incidence of gastric cancer effectively. At present, the object detection method based on deep learning is widely used in medical images. However, as the contrast between the background and the polyps is not strong in gastroscopic image, it is difficult to distinguish various sizes of polyps from the background. In this paper, to improve the detection performance metrics of endoscopic gastric polyps, we propose an improved attentional feature fusion module. First, in order to enhance the contrast between the background and the polyps, we propose an attention module that enables the network to make full use of the target location information, it can suppress the interference of the background information and highlight the effective features. Therefore, on the basis of accurate positioning, it can focus on detecting whether the current location is the gastric polyp or background. Then, it is combined with our feature fusion module to form a new attentional feature fusion model that can mitigate the effects caused by semantic differences in the processing of feature fusion, using multi-scale fusion information to obtain more accurate attention weights and improve the detection performance of polyps of different sizes. In this work, we conduct experiments on our own dataset of gastric polyps. Experimental results show that the proposed attentional feature fusion module is better than the common feature fusion module and can improve the situation where polyps are missed or misdetected.

Soy leghemoglobin, when bound to heme, imparts a meat-like color and flavor and can serve as a substitute for animal-derived proteins. Enhancing cellular heme synthesis improves the recombinant expression of leghemoglobin in yeast. To achieve high-level expression of leghemoglobin A (LBA) in Kluyveromyces marxianus, a food-safe yeast, large-scale heme synthesis modules were transferred into K. marxianus using yeast artificial chromosomes (KmYACs). These modules contained up to 8 native and heterologous genes to promote the supply of heme precursors and downstream synthesis. Next, eight genes inhibiting heme or LBA synthesis were individually or combinatorially deleted, with the lsc1Δssn3Δ mutant yielding the best results. Subsequently, heme synthesis modules were combined with the lsc1Δssn3Δ mutant. In the resulting strains, the module genes were all actively expressed. Among these module genes, heterologous S. cerevisiae genes in the downstream heme synthesis pathway significantly enhanced the expression of their counterparts in K. marxianus, resulting in high heme content and LBA yield. After optimizing the medium recipe by adjusting the concentrations of glucose, glycine, and FeSO4·7H2O, a heme content of 66.32 mg/L and an intracellular LBA titer of 7.27 g/L were achieved in the engineered strain in a 5 L fermentor. This represents the highest intracellular expression of leghemoglobin in microorganisms to date. The leghemoglobin produced by K. marxianus can be utilized as a safe ingredient for plant-based protein products.

We study the Zcs(3985) and Zcs(4000) exotic states in the decays of Λb baryons through a molecular scenario. In the final state interaction, the Λb→Λc+Ds(⁎)− decays are followed by the Λc+Ds(⁎)− to Zcs−p rescatterings via exchange of a D(⁎) meson. We predict a branching fraction of (3.1−2.6+1.4)×10−4 for Λb→Zcs−p, which can be measured in the Λb→J/ψK(⁎)−p decay. This study proposes a new approach to test the molecular model, and guides future experimental searches for the Zcs(3985) and Zcs(4000).

ABSTRACT Broccoli is increasingly favored by consumers as it is rich in vitamins and many other bioactive compounds. However, existing large tractor-drawn vegetable harvesting machinery is more suitable for large farmland and farm cultivation patterns. Therefore, this paper develops tracked broccoli harvesting equipment for small farmland and tests the ability to harvest broccoli. The tracked broccoli harvester developed in this paper is capable of traveling on its own in the field, cutting the stalks and transporting the broccoli bulbs. This paper analyses the working process of the cutting device and designs the working parameters. Through the cutting bench experiment, the optimal working parameters of the cutting device were determined as 456 r/min of rotational speed, 8.312 mm of overlap, and 0.255 m/s of pusher speed. In the field test, the broccoli leakage rate was 4.8%, the cutting qualification rate was 81.6%, the transport qualification rate was 95.62%, the damage rate was 3.96%, and the total loss rate was 8.55%. This structural model is an important technical support for broccoli harvesting equipment in China.

AbstractThe aim of the study was to investigate the biomechanical behavior of three-dimensionally (3D)-printed surgical plates used for mandibular defect reconstruction, compare them with conventional surgical plates, and provide experimental evidence for their clinical application. Three-dimensional models were created for the normal mandible and for mandibular body defects reconstructed using free fibula and deep circumflex iliac artery flaps. Three-dimensional finite element models of reconstructed mandibles fixed using 3D-printed and conventional surgical plates were established. Vertical occlusal forces were applied to the remaining teeth and the displacement and Von Mises stress distributions were studied using finite element analysis. The normal and reconstructed mandibles had similar biomechanical behaviors. The displacement distributions for the surgical plates were similar, and the maximum total deformation occurred at the screw hole of the anterior segment of the surgical plates. However, there were differences in the Von Mises stress distributions for the surgical plates. In reconstructed mandibles fixed using 3D-printed surgical plates, the maximum equivalent Von Mises stress occurred at the screw hole of the posterior segment, while in those fixed using conventional surgical plates, the maximum equivalent Von Mises stress was at the screw hole of the anterior segment. In the mandible models reconstructed with the same free flap but fixed with different surgical plates, the plates had similar biomechanical behaviors. The biomechanical behavior of 3D-printed surgical plates was similar to conventional surgical plates, suggesting that 3D-printed surgical plates used to reconstruct mandibular body defects with vascularized autogenous bone grafts could lead to secure and stable fixation.

Abstract The quantitative control of FLOWERING LOCUS T (FT) activation is important for the floral transition in flowering plants. However, the flowering regulation mechanisms in the day-neutral, summer-flowering chrysanthemum plant remain unclear. In this study, the chrysanthemum BBX7 homolog CmBBX7 was isolated and its flowering function was identified. The expression of CmBBX7 showed a diurnal rhythm and CmBBX7 exhibited higher expression levels than CmBBX8. Overexpression of CmBBX7 in transgenic chrysanthemum accelerated flowering, whereas lines transfected with a chimeric repressor (pSRDX-CmBBX7) exhibited delayed flowering. Yeast single hybridization, luciferase, electrophoretic mobility shift, and chromatin immunoprecipitation assays showed that CmBBX7 directly targets CmFTL1. In addition, we found that CmBBX7 and CmBBX8 interact to positively regulate the expression of CmFTL1 through binding to its promoter. Collectively, these results highlight CmBBX7 as a key cooperator in the BBX8–FT module to control chrysanthemum flowering. Graphical Abstract

The dysregulation of the m6A epitranscriptomic networks have been reported to contribute to the development of gliomas. Here, the authors utilize induced pluripotent stem cell-derived astrocytes with a p53 mutation and demonstrate that mutant p53 upregulates the m6A reader YTHDF2, resulting in the initiation of gliomas.

A series of well-defined diblock copolymers, namely, 3,4-polyisoprene-block-syndiotactic-1,2-polybutadiene (3,4-PI-b-s-1,2-PBD), with a soft–hard block sequence were synthesized via an in situ sequential polymerization process using a robust iron-based catalytic system Fe(acac)3/(isocyanoimino) triptenylphosphorane (IITP)/AliBu3. This catalyst exhibits vigorous activity and temperature tolerance, achieving a polymerization activity of 5.41 × 106 g mol(Fe)−1 h−1 at 70 °C with a [IP]/[Fe] ratio of 15,000. Moreover, the quasi-living polymerization characteristics of the catalyst were verified through kinetic experiments. The first-stage polymerization of isoprene (IP) is performed at 30 °C to give a soft 3,4-PI block, and then a quantitative amount of 1,3-butadiene was added in situ to the quasi-living polymerization system to produce a second hard s-1,2-PBD. The s-1,2-PBD segments in block copolymers display a rodlike morphology contrasting with the spherulitic morphology characteristic of s-1,2-PBD homopolymers. The precise tunability of the length of the soft and hard chain segments of these novel elastic materials with the feed ratio of IP and BD, endowing them with outstanding mechanical properties and excellent dynamic mechanical properties, which are expected to be promising high-performance rubber materials.

AbstractThe Kazakhs of Xinjiang province are characterized by their nomadic lifestyle and patrilineal clan system. However, compared to Central Asian Kazakhs, a lack of Y chromosomal high-resolution analysis has hindered our understanding of the paternal history of modern Xinjiang Kazakhs.MethodsIn this study, we present the analysis of 110 Y-SNP data from 209 Altay Kazakhs and 201 Ili Kazakhs in Xinjiang, along with their previously reported 24 Y-STR loci data.Results and discussionWe found that the Y chromosome haplogroups exhibit greater diversity in Altay Kazakhs compared to Kazakhs in Kazakhstan, Russia, and other regions of China. Y-SNP-based PCA plots reveal that both the Altay and Ili Kazakhs are situated between the Turkic, Mongolia, and Tibeto-Burman clusters. The dominant haplogroup C2a1a3-F1918, which originated in northeast Asia during the Neolithic Age, accounts for nearly half of the Altay and Ili Kazakhs. The Y lineage network of C2a1a3-F1918 contained two subclusters. Approximately 60.6% of the Altay Kazakhs belong to the DYS448-23 subcluster, indicating their Kerey-Abakh ancestry. On the other hand, around three-quarters of the Ili Kazakhs belong to the DYS448-22 subcluster, suggesting their Kerey-Ashmaily heritage. Notably, the TMRCA ages of the DYS448-23 subcluster were calculated to be 289.4 ± 202.65 years, which aligns with the historical immigration of the Kerey clan back to the Altay Mountains after the defeat of the Dzungar by the Qing dynasty in the mid-18th century.

IntroductionGenerally, Traditional Chinese Medicine (TCM) courses are now given to modern medicine students without proper course scheduling, resulting in poor teaching results.MethodsTo analyze the main factors affecting TCM learning, we surveyed the medical students and TCM teachers from Xiangya School of Medicine of Central South University via online questionnaires. The questionnaire comprised two parts, the students' part included the basic information, the subjective cognition in TCM, the attitude toward TCM course arrangements, and the attitude toward curriculum content and the design of TCM. The teachers' part included the basic information, the attitudes and opinions on TCM course arrangements, and suggestions and views on TCM teaching reform. The related data were collected from 187 medical students divided into two groups, namely, clinical medical students and non-clinical medical students.ResultsWe found a more positive attitude toward TCM [including “Scientific nature of TCM” (P = 0.03) and “Necessity for modern medicine students to learn TCM” (P = 0.037)] in clinical medical students compared with non-clinical medical students, clinical and non-clinical medical students tended to find TCM courses difficult, and the students prefer clinical training to be better than theoretical teaching, while the teachers believe that lecture-based education should have a more significant proportion.DiscussionHence, to optimize the current TCM teaching, we conducted education reform, including differentiated teaching, hybrid teaching, and selective teaching.