Search

Guohuan Chen, Qingyu Lin, Debin Zhuo, Jinhe Cui Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Putian University, Putian, People’s Republic of ChinaCorrespondence: Guohuan Chen, Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Putian University, 999 Dongzhen East Road, Licheng District, Putian City, 351100, Fujian Province, People’s Republic of China, Tel +86-594-2730387, Email chenguohuanpt@163.comBackground: To evaluate the association of elevated blood glucose with the risk of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD).Methods: Totally 526 consecutive patients with COPD recruited between Jan. 2018 and July 2019 were included in this study. Based on the American Diabetes Association’s Standards of Care, these patients were divided into three groups according to HbA1c level: low HbA1c level (HbA1c < 5.7%, n=204), moderate HbA1c level (HbA1c 5.7– 6.4%, n=165), and high HbA1c level (HbA1c ≥ 6.5%, n=157). All subjects were followed up for 18 months. Multivariate Cox regression analysis was used to evaluate the predicting value of HbA1c for the time of the next COPD severe exacerbation.Results: Totally 141 (26.8%) patients in the study had at least 1 severe exacerbation. The proportion of patients suffering from at least 1 severe exacerbation was significantly higher (P< 0.01) for patients with high (36.3%) and moderate HbA1c levels (25.5%) compared to those with low HbA1c levels (20.6%). Multivariate Cox regression analysis indicated that high (HR=2.74, 95% CI: 1.70– 4.41; P< 0.01) and moderate HbA1c levels (HR=2.19, 95% CI: 1.39– 3.46; P< 0.01) were significantly associated with a higher risk of the next severe exacerbation compared with low HbA1c level, after controlling for potential confounders including age, gender, body mass index (BMI), smoking status, disease duration of COPD, frequency of hospitalization due to acute exacerbation of COPD (AECOPD) in the past 12 months, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, COPD assessment test (CAT) score, corticosteroids use, hypertension, and cardiovascular diseases. Subgroup analyses also indicated a significant association between HbA1c levels and risk of the next severe exacerbation in different GOLD stages and diabetes status.Conclusion: Elevated blood glucose, no matter with or without diabetes, is significantly associated with a higher risk of the next severe exacerbation for patients with COPD.Keywords: blood glucose, HbA1c, COPD, severe exacerbation

Li Cheng,1,* Hao Wang,2,* Zicheng Wang,3 Houbao Huang,1 Dong Zhuo,1 Jian Lin4 1Department of Urology, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 2Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 4Department of Urology, Peking University First Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Cheng Email chenglibjmu@163.comIntroduction: Bladder cancer is a lethal human malignancy. Currently, treatment for bladder cancer is limited. The anti-tumor effects of leflunomide have attracted much more concern in multiple human cancers.Materials and Methods: This study evaluated the anti-tumor effects of leflunomide on cell viability, colony formation, apoptosis, and cell cycle in two human bladder carcinoma cell lines, 5637 and T24. Meanwhile, the underlying mechanism including PI3K/Akt signaling pathway and autophagy modulation was also identified.Results: Leflunomide markedly inhibited the growth of both bladder cancer cell lines and induced apoptosis and cell cycle arrest in S phase. The phosphorylation levels of Akt and P70S6K in both cell lines were significantly down-regulated with leflunomide treatment. Furthermore, the deceased formation of autophagosomes and the accumulation of LC3II and P62 suggested the blockade of autophagy by leflunomide. Modulation of autophagy with rapamycin and chloroquine markedly attenuated and enhanced the cytostatic effects of leflunomide, respectively.Conclusion: Leflunomide significantly reduced the cell viability of bladder cancer cells via inducing apoptosis and cell cycle arrest and suppressing the PI3K/Akt signaling pathway. In addition, the blockade of autophagy was observed, and autophagy inhibition enhanced leflunomide-mediating anti-tumor effects. Our data presented here offer novel ideas for comprehensive therapeutic regimes on bladder cancer.Keywords: leflunomide, autophagy, PI3K/Akt pathway, anti-tumor, bladder cancer

Abstract Transcranial direct current stimulation (tDCS) is a promising noninvasive intervention for Parkinson’s disease (PD). However, studies of its motor and cognitive effect have produced mixed results. We conducted a systematic review including 38 studies and meta-analysis of 12 randomized sham-controlled trials with 263 PD patients. No significant differences were found between active and sham tDCS in motor function (UPDRS-III: SMD = –0.14, p = 0.74), gait (SMD = 0.10, p = 0.513), attention and working memory (SMD = 0.24, p = 0.13), executive function (SMD = 0.03, p = 0.854), and memory and learning (SMD: −0.07, p = 0.758). The prediction intervals indicated substantial heterogeneity among studies. Meta-regression showed small positive effects in younger PD patients with milder symptoms. These findings are preliminary but suggest tDCS may benefit some PD patients while being neutral or harmful to others.

Abstract The electronic medical record management system plays a crucial role in clinical practice, optimizing the recording and management of healthcare data. To enhance the functionality of the medical record management system, this paper develops a customized schema designed for ophthalmic diseases. A multi-modal knowledge graph is constructed, which is built upon expert-reviewed and de-identified real-world ophthalmology medical data. Based on this data, we propose an auxiliary diagnostic model based on a contrastive graph attention network (CGAT-ADM), which uses the patient’s diagnostic results as anchor points and achieves auxiliary medical record diagnosis services through graph clustering. By implementing contrastive methods and feature fusion of node types, text, and numerical information in medical records, the CGAT-ADM model achieved an average precision of 0.8563 for the top 20 similar case retrievals, indicating high performance in identifying analogous diagnoses. Our research findings suggest that medical record management systems underpinned by multimodal knowledge graphs significantly enhance the development of AI services. These systems offer a range of benefits, from facilitating assisted diagnosis and addressing similar patient inquiries to delving into potential case connections and disease patterns. This comprehensive approach empowers healthcare professionals to garner deeper insights and make well-informed decisions.

Objective: This study aimed to explore the effect of comprehensive noise reduction management on the postoperative recovery of burn patients. Methods: Data of 156 patients admitted to Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from October 2022 to July 2023 were retrospectively analysed. The patients were divided into two groups according to the management method: group A (n = 76, standard care of burns) and group B (n = 80, standard care of burns+comprehensive noise reduction management). The stress response level, anxiety and depression level, sleep quality and satisfaction of the two groups were compared before and after the management. Results: Before the management, no statistically significant differences in cortisol (Cor), anxiety and depression scores and sleep quality were found between the two groups (P > 0.05). After the management, significant differences in Cor, anxiety scores, sleep quality and patient satisfaction were observed between the two groups (P < 0.001). Conclusions: Comprehensive noise reduction management can reduce postoperative stress hormone levels, alleviate negative emotions, such as anxiety, and improve sleep quality and patient satisfaction.

Abstract Ovarian cancer is an extremely malignant gynaecological tumour with a poor patient prognosis and is often associated with chemoresistance. Thus, exploring new therapeutic approaches to improving tumour chemosensitivity is important. The expression of transcription elongation factor B polypeptide 2 (TCEB2) gene is reportedly upregulated in ovarian cancer tumour tissues with acquired resistance, but the specific mechanism involved in tumour resistance remains unclear. In this study, we found that TCEB2 was abnormally highly expressed in cisplatin-resistant tumour tissues and cells. TCEB2 silencing also inhibited the growth and glycolysis of SKOV-3/cisplatin (DDP) and A2780/DDP cells. We further incubated human umbilical vein endothelial cells (HUVECs) with culture supernatants from cisplatin-resistant cells having TCEB2 knockdown. Results revealed that the migration, invasion, and angiogenesis of HUVECs were significantly inhibited. Online bioinformatics analysis revealed that the hypoxia-inducible factor-1A (HIF-1A) protein may bind to TCEB2, and TCEB2 silencing inhibited SKOV-3/DDP cell growth and glycolysis by downregulating HIF1A expression. Similarly, TCEB2 promoted HUVEC migration, invasion, and angiogenesis by upregulating HIF1A expression. In vivo experiments showed that TCEB2 silencing enhanced the sensitivity of ovarian cancer nude mice to cisplatin and that TCEB2 knockdown inhibited the glycolysis and angiogenesis of tumour cells. Our findings can serve as a reference for treating chemoresistant ovarian cancer.

Abstract Antibacterial therapy targeting the regulation of macrophage polarization may be a useful approach for normalizing the immune environment and accelerating wound healing. Inspired by black phosphorus‐based nanoplatforms, more stable yet less‐explored violet phosphorus nanosheets (VPNSs) are expected to provide a superior solution for effectively combating bacterial infections. In this study, an average thickness of 5–7 nm VPNSs are fabricated through the liquid‐phase exfoliation method to serve as an immunoregulatory dressing for the treatment of infected wounds. VPNSs attenuated excessive reactive oxygen species (ROS) and reduced the accumulation of proinflammatory M1 macrophages, showing notable antioxidant and anti‐inflammatory properties. Comprehensive RNA sequencing further elucidated the potential immunoregulatory mechanisms of VPNSs, including modulation of the inflammatory response and enzyme regulator activity. Additionally, the inherent photothermal properties of the VPNSs contributed significantly to their antibacterial efficacy. When combined with near‐infrared laser irradiation, VPNSs showed remarkable effectiveness in reducing infection‐related complications and expediting wound healing in infected skin wound models. The rapid promotion of wound healing through ROS clearance, the regulation of macrophage polarization, and hyperthermia generation underscores the potential of the violet‐phosphorus‐based nanoplatforms as clinically viable agents for treating infected wounds. This study suggests that VPNSs are promising candidates for clinical anti‐infective and anti‐inflammatory applications.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway plays a crucial role in the viral immune processes of organisms, with STAT being a key transcription factor downstream in this pathway. The STAT gene of Bombyx mori has two splicing forms, named BmSTAT-S and BmSTAT-L. This study compared the effects of the two splicing forms on Bombyx mori nucleopolyhedrovirus (BmNPV) infection through cell-level interference and further explored whether BmSTAT participates in the immune response to BmNPV infection via transgenic intervention at the individual level. Our research results indicated that BmNPV upregulates the expression of BmSTAT-S and BmSTAT-L in Bombyx mori BmE cells and larvae. Furthermore, BmE cells with interference of BmSTAT-S or BmSTAT-L displayed significantly higher expression levels of the viral gene GP41 and increased viral fluorescence compared to the control group after 48 h of infection with BmNPV. Then, we constructed transgenic silkworms with genetic interference, and the results showed that both the transgenic silkworms with systemic interference and midgut-specific interference of the two splice forms of BmSTAT exhibited significantly reduced survival rates and increased viral replication numbers after infection with BmNPV. The above results indicated that the BmSTAT gene is involved in the immune response of Bombyx mori to BmNPV and these findings lay the foundation for further research on the mechanism of JAK/STAT signaling pathway involvement in BmNPV infection.

Abrasive water jet is a highly efficient cutting technology. Through some sandstone cutting tests, the research on the optimal impact angle and inclined cutting mechanism of rock-like materials is carried out. Based on the macroscopic and microscopic observation of the cut’s inner wall, crystal glass cutting experiments are conducted to investigate the cutting motion process of abrasive water jet under different impact angles, revealing the variation laws of cutting depth, the characteristics of the cut’s inner wall, the trajectory of abrasive particles and the type of crystal destruction under different cutting pressures and impact angles. The test results show that the average cutting depth gradually increases with the increase of cutting pressure, while changing the impact angle can significantly change the jet’s cutting ability, and the best cutting effect is obtained at an impact angle of 75°. With the increase of the cut depth, the curved jet trajectory texture gradually appears in the cut’s inner wall , and in its bottom there are typical erosion pits and trailing phenomenon. The cut’s inner wall is mainly characterized by four types of damage features such as fracture through the crystal, fracture along the crystal, cut grooves or pits, and cement coverage, etc. It is worth noting that the four types of damage features appear at different locations in the cut at different impact angles, and this phenomenon is mainly caused by the deflection of jet, the direction of reflected flow movement, and the change in the reflection of shock wave and expansion wave. The vertical and horizontal jet components (in the same direction as the direction of propulsion), which play a dominant role in the destruction of the target, and the horizontal jet component, which is opposite to the direction of propulsion, play a secondary role in the erosion and polishing of the formed cut, but the degree of action varies under different impact angles. The macroscopic model of the abrasive water jet cutting process is established by combining the trajectory texture of cut’s inner wall and the observation results of the jet cutting process. The research results can provide a technical reference for further improving the efficiency of abrasive water jet cutting.

The geometry of joints has a significant influence on the mechanical properties of rocks. To simplify the curved joint shapes in rocks, the joint shape is usually treated as straight lines or planes in most laboratory experiments and numerical simulations. In this study, the computerized tomography (CT) scanning and photogrammetry were employed to obtain the internal and surface joint structures of a limestone sample, respectively. To describe the joint geometry, the edge detection algorithms and a three-dimensional (3D) matrix mapping method were applied to reconstruct CT-based and photogrammetry-based jointed rock models. For comparison tests, the numerical uniaxial compression tests were conducted on an intact rock sample and a sample with a joint simplified to a plane using the parallel computing method. The results indicate that the mechanical characteristics and failure process of jointed rocks are significantly affected by the geometry of joints. The presence of joints reduces the uniaxial compressive strength (UCS), elastic modulus, and released acoustic emission (AE) energy of rocks by 37%–67%, 21%–24%, and 52%–90%, respectively. Compared to the simplified joint sample, the proposed photogrammetry-based numerical model makes the most of the limited geometry information of joints. The UCS, accumulative released AE energy, and elastic modulus of the photogrammetry-based sample were found to be very close to those of the CT-based sample. The UCS value of the simplified joint sample (i.e. 38.5 MPa) is much lower than that of the CT-based sample (i.e. 72.3 MPa). Additionally, the accumulative released AE energy observed in the simplified joint sample is 3.899 times lower than that observed in the CT-based sample. CT scanning provides a reliable means to visualize the joints in rocks, which can be used to verify the reliability of photogrammetry techniques. The application of the photogrammetry-based sample enables detailed analysis for estimating the mechanical properties of jointed rocks.

Abstract During myocardial ischaemia‒reperfusion injury (MIRI), the accumulation of damaged mitochondria could pose serious threats to the heart. The migrasomes, newly discovered mitocytosis‐mediating organelles, selectively remove damaged mitochondria to provide mitochondrial quality control. Here, we utilised low‐intensity pulsed ultrasound (LIPUS) on MIRI mice model and demonstrated that LIPUS reduced the infarcted area and improved cardiac dysfunction. Additionally, we found that LIPUS alleviated MIRI‐induced mitochondrial dysfunction. We provided new evidence that LIPUS mechanical stimulation facilitated damaged mitochondrial excretion via migrasome‐dependent mitocytosis. Inhibition the formation of migrasomes abolished the protective effect of LIPUS on MIRI. Mechanistically, LIPUS induced the formation of migrasomes by evoking the RhoA/Myosin II/F‐actin pathway. Meanwhile, F‐actin activated YAP nuclear translocation to transcriptionally activate the mitochondrial motor protein KIF5B and Drp1, which are indispensable for LIPUS‐induced mitocytosis. These results revealed that LIPUS activates mitocytosis, a migrasome‐dependent mitochondrial quality control mechanism, to protect against MIRI, underlining LIPUS as a safe and potentially non‐invasive treatment for MIRI.

Two new Cortinarius species in subgenus Leprocybe, Cortinarius hengduanensis and C. yadingensis, are proposed based on a combination of morphological and molecular evidence. Cortinarius hengduanensis has distinct olive tinged basidiomata, a squamulose pileus, and small, subglobose to broadly ellipsoid basidiospores, the ITS sequence differs from that of C. flavifolium by at least 28 substitutions and independent positions. Cortinarius yadingensis has a squamulose pileus and subglobose to broadly ellipsoid coarsely verrucose basidiospores, the ITS sequence has at least 11 substitutions and index position deviations from the other members of the Leprocybe section. Both new species were found in mixed forests of southwest China.

Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs in Caenorhabditis elegans. The absence of NuRD triggers apoptosis via the EGL-1-CED-9-CED-4-CED-3 pathway, while an ectopic gain of NuRD enables apoptotic daughter cells to survive. We identify the vacuolar H+–adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD’s asymmetric segregation. V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates.

Abstract Elucidating the expression of microRNAs in developing single cells is critical for functional discovery. Here, we construct scCAMERA (single-cell cartography of microRNA expression based on reporter assay), utilizing promoter-driven fluorescent reporters in conjunction with imaging and lineage tracing. The cartography delineates the transcriptional activity of 54 conserved microRNAs in lineage-resolved single cells throughout C. elegans embryogenesis. The combinatorial expression of microRNAs partitions cells into fine clusters reflecting their function and anatomy. Notably, the expression of individual microRNAs exhibits high cell specificity and divergence among family members. Guided by cellular expression patterns, we identify developmental functions of specific microRNAs, including miR-1 in pharynx development and physiology, miR-232 in excretory canal morphogenesis by repressing NHR-25/NR5A, and a functional synergy between miR-232 and miR-234 in canal development, demonstrating the broad utility of scCAMERA. Furthermore, integrative analysis reveals that tissue-specific fate determinants activate microRNAs to repress protein production from leaky transcripts associated with alternative, especially neuronal, fates, thereby enhancing the fidelity of developmental fate differentiation. Collectively, our study offers rich opportunities for multidimensional expression-informed analysis of microRNA biology in metazoans.

In this paper, we present our process design kits (PDKs) component performances for different wavelengths in the visible to near-infrared (VIS-NIR) range on Shanghai Industrial μTechnology Research Institute's (SITRI's) 200 mm silicon nitride (SiN) photonics platform. SiN waveguide platform has emerged as a promising technology due to its low optical loss, relatively high refractive index, and transparency across the VIS-NIR spectrum. The industrialization of SiN platforms requires matured PDKs. On SITRI's 200 mm SiN photonics platform, we developed PDKs using both Plasma-Enhanced Chemical Vapor Deposition (PECVD) and Low-Pressure Chemical Vapor Deposition (LPCVD) processes, with SiN layers of 180 nm and 150 nm thicknesses, respectively. The fabricated waveguides exhibit low propagation loss, ranging from 2.5 dB/cm to 0.34 dB/cm from 532 nm to 860 nm. Additionally, we present a low bending loss which is less than 0.06 dB/90° with a radius of 100 μm. Furthermore, the loss of the linear grating coupler (LGC) is less than 2.6 dB at 785 nm. We have also achieved low-loss splitters, including 1 × 2 multimode interference (MMI) coupler, and directional coupler (DC), with a minimum excess loss of 0.03 dB. Additionally, micro ring resonator with high quality (Q) factors of 146,000 has been demonstrated. Our work on developing these PDKs will open new opportunities for researchers and developers to design and fabricate advanced photonic devices on the SiN platform in SITRI's 200 mm fabrication line.

The segmentation of fundus tumors is critical for ophthalmic diagnosis and treatment, yet it presents unique challenges due to the variability in lesion size and shape. Our study introduces Fundus Tumor Segmentation Network (FTSNet), a novel segmentation network designed to address these challenges by leveraging classification results and prompt learning. Our key innovation is the multiscale feature extractor and the dynamic prompt head. Multiscale feature extractors are proficient in eliciting a spectrum of feature information from the original image across disparate scales. This proficiency is fundamental for deciphering the subtle details and patterns embedded in the image at multiple levels of granularity. Meanwhile, a dynamic prompt head is engineered to engender bespoke segmentation heads for each image, customizing the segmentation process to align with the distinctive attributes of the image under consideration. We also present the Fundus Tumor Segmentation (FTS) dataset, comprising 254 pairs of fundus images with tumor lesions and reference segmentations. Experiments demonstrate FTSNet’s superior performance over existing methods, achieving a mean Intersection over Union (mIoU) of 0.8254 and mean Dice (mDice) of 0.9042. The results highlight the potential of our approach in advancing the accuracy and efficiency of fundus tumor segmentation.

The functionally graded (FG) flexoelectric material is a potential material to determine the structural morphing of aircrafts. This work proposes the penalty 20-node element based on the consistent couple stress theory for analyzing the FG flexoelectric plate and shell structures with complex geometric shapes and loading conditions. Several numerical examples are examined and prove that the new element can predict the size-dependent behaviors of FG flexoelectric plate and shell structures effectively, showing good convergence and robustness. Moreover, the numerical results reveal that FG flexoelectric material exhibits better bending performance and higher flexoelectric effect compared to homogeneous materials. Moreover, the increase in the material length scale parameter leads to a gradual increase in the natural frequencies of the out-of-plane modes of FG flexoelectric plate/shell, while the natural frequencies of the in-plane modes change minimally, resulting in the occurrence of mode-switching phenomena.

Osteonecrosis (ON) of the femoral head (ONFH) is a devastating bone disease affecting over 20 million people worldwide. ONFH is caused by a disruption of the blood supply, leading to necrotic cell death and increased inflammation. Macrophages are the key cells mediating the inflammatory responses in ON. It is unclear what the dynamic phenotypes of macrophages are and what mechanisms may affect macrophage polarization and, therefore, the healing process. In our preliminary study, we found that there is an invasion of macrophages into the repair tissue during ON healing. Interestingly, in both ONFH patients and a mouse ON model, fat was co-labeled within macrophages using immunofluorescence staining, indicating the phagocytosis of fat by macrophages. To study the effects of fat phagocytosis on the macrophage phenotype, we set up an in vitro macrophage and fat co-culture system. We found that fat phagocytosis significantly decreased M1 marker expression, such as IL1β and iNOS, in macrophages, whereas the expression of the M2 marker Arg1 was significantly increased with fat phagocytosis. To investigate whether the polarization change is indeed mediated by phagocytosis, we treated the cells with Latrunculin A (LA, which inhibits actin polymerization and phagocytosis). LA supplementation significantly reversed the polarization marker gene changes induced by fat phagocytosis. To provide an unbiased transcriptional gene analysis, we submitted the RNA for bulk RNA sequencing. Differential gene expression (DGE) analysis revealed that the top upregulated genes were related to anti-inflammatory responses, while proinflammatory genes were significantly downregulated. Additionally, using pathway enrichment and network analyses (Metascape), we confirmed that gene-enriched categories related to proinflammatory responses were significantly downregulated in macrophages with fat phagocytosis. Finally, we validated the similar macrophage phenotype changes in vivo. To summarize, we discovered that fat phagocytosis occurs in both ONFH patients and an ON mouse model, which inhibits proinflammatory responses with increased anabolic gene expression in macrophages. This fat-phagocytosis-induced macrophage phenotype is consistent with the in vivo changes shown in the ON mouse model. Our study reveals a novel phagocytosis-mediated macrophage polarization mechanism in ON, which fills in our knowledge gaps of macrophage functions and provides new concepts in macrophage immunomodulation as a promising treatment for ON.

Abstract Therapeutic tumor vaccines have attracted considerable attention in the past decade; they can induce tumor regression, eradicate minimal residual disease, establish lasting immune memory and avoid non-specific and adverse side effects. However, the challenge in the field of therapeutic tumor vaccines is ensuring the delivery of immune components to the lymph nodes (LNs) to activate immune cells. The clinical response rate of traditional therapeutic tumor vaccines falls short of expectations due to inadequate lymph node delivery. With the rapid development of nanotechnology, a large number of nanoplatform-based LN-targeting nanovaccines have been exploited for optimizing tumor immunotherapies. In addition, some nanovaccines possess non-invasive visualization performance, which is benefit for understanding the kinetics of nanovaccine exposure in LNs. Herein, we present the parameters of nanoplatforms, such as size, surface modification, shape, and deformability, which affect the LN-targeting functions of nanovaccines. The recent advances in nanoplatforms with different components promoting LN-targeting are also summarized. Furthermore, emerging LNs-targeting nanoplatform-mediated imaging strategies to both improve targeting performance and enhance the quality of LN imaging are discussed. Finally, we summarize the prospects and challenges of nanoplatform-based LN-targeting and /or imaging strategies, which optimize the clinical efficacy of nanovaccines in tumor immunotherapies.

Summary: Elucidating the complex relationships between mRNA and protein expression at high spatiotemporal resolution is critical for unraveling multilevel gene regulation and enhancing mRNA-based developmental analyses. In this study, we conduct a single-cell analysis of mRNA and protein expression of transcription factors throughout C. elegans embryogenesis. Initially, cellular co-presence of mRNA and protein is low, increasing to a medium-high level (73%) upon factoring in delayed protein synthesis and long-term protein persistence. These factors substantially affect mRNA-protein concordance, leading to potential inaccuracies in mRNA-reliant gene detection and specificity characterization. Building on the learned relationship, we infer protein presence from mRNA expression and demonstrate its utility in identifying tissue-specific genes and elucidating relationships between genes and cells. This approach facilitates identifying the role of sptf-1/SP7 in neuronal lineage development. Collectively, this study provides insights into gene expression dynamics during rapid embryogenesis and approaches for improving the efficacy of transcriptome-based developmental analyses.

Pattern formation originates during embryogenesis by a series of symmetry-breaking steps throughout an expanding cell lineage. In Drosophila, classic work has shown that segmentation in the embryo is established by morphogens within a syncytium, and the subsequent action of the gap, pair-rule, and segment polarity genes. This classic model however does not translate directly to species that lack a syncytium – such as Caenorhabditis elegans – where cell fate is specified by cell-autonomous cell lineage programs and their inter-signaling. Previous single-cell RNA-Seq studies in C. elegans have analyzed cells from a mixed suspension of cells from many embryos to study late differentiation stages, or individual early stage embryos to study early gene expression in the embryo. To study the intermediate stages of early and late gastrulation (28- to 102-cells stages) missed by these approaches, here we determine the transcriptomes of the 1- to 102-cell stage to identify 119 embryonic cell states during cell fate specification, including ‘equivalence-group’ cell identities. We find that gene expression programs are modular according to the sub-cell lineages, each establishing a set of stripes by combinations of transcription factor gene expression across the anterior-posterior axis. In particular, expression of the homeodomain genes establishes a comprehensive lineage-specific positioning system throughout the embryo beginning at the 28-cell stage. Moreover, we find that genes that segment the entire embryo in Drosophila have orthologs in C. elegans that exhibit sub-lineage-specific expression. These results suggest that the C. elegans embryo is patterned by a juxtaposition of distinct lineage-specific gene regulatory programs each with a unique encoding of cell location and fate. This use of homologous gene regulatory patterning codes suggests a deep homology of cell fate specification programs across diverse modes of development.

Background: Our study aims to develop an artificial intelligence-based high-precision cataract classification and grading evaluation network using fundus images.Methods: We utilized 1,340 color fundus photographs from 875 participants (aged 50–91 years at image capture) from the Beijing Eye Study 2011. Four experienced and trained ophthalmologists performed the classification of these cases based on slit-lamp and retro-illuminated images. Cataracts were classified into three types based on the location of the lens opacity: cortical cataract, nuclear cataract, and posterior subcapsular cataract. We developed a Dual-Stream Cataract Evaluation Network (DCEN) that uses color photographs of cataract fundus to achieve simultaneous cataract type classification and severity grading. The accuracy of severity grading was enhanced by incorporating the results of type classification.Results: The DCEN method achieved an accuracy of 0.9762, a sensitivity of 0.9820, an F1 score of 0.9401, and a kappa coefficient of 0.8618 in the cataract classification task. By incorporating type features, the grading of cataract severity can be improved with an accuracy of 0.9703, a sensitivity of 0.9344, an F1 score of 0.9555, and a kappa coefficient of 0.9111. We utilized Grad-CAM visualization technology to analyze and summarize the fundus image features of different types of cataracts, and we verified our conclusions by examining the information entropy of the retinal vascular region.Conclusion: The proposed DCEN provides a reliable ability to comprehensively evaluate the condition of cataracts from fundus images. Applying deep learning to clinical cataract assessment has the advantages of simplicity, speed, and efficiency.

The accurate segmentation and quantification of retinal fluid in Optical Coherence Tomography (OCT) images are crucial for the diagnosis and treatment of ophthalmic diseases such as age-related macular degeneration. However, the accurate segmentation of retinal fluid is challenging due to significant variations in the size, position, and shape of fluid, as well as their complex, curved boundaries. To address these challenges, we propose a novel multi-scale feature fusion attention network (FNeXter), based on ConvNeXt and Transformer, for OCT fluid segmentation. In FNeXter, we introduce a novel global multi-scale hybrid encoder module that integrates ConvNeXt, Transformer, and region-aware spatial attention. This module can capture long-range dependencies and non-local similarities while also focusing on local features. Moreover, this module possesses the spatial region-aware capabilities, enabling it to adaptively focus on the lesions regions. Additionally, we propose a novel self-adaptive multi-scale feature fusion attention module to enhance the skip connections between the encoder and the decoder. The inclusion of this module elevates the model’s capacity to learn global features and multi-scale contextual information effectively. Finally, we conduct comprehensive experiments to evaluate the performance of the proposed FNeXter. Experimental results demonstrate that our proposed approach outperforms other state-of-the-art methods in the task of fluid segmentation.

ABSTRACT Obesity is a risk factor for the development of hyperuricemia, both of which were related to gut microbiota. However, whether alterations in the gut microbiota lie in the pathways mediating obesity’s effects on hyperuricemia is less clear. Body mass index (BMI) and serum uric acid (SUA) were separately important indicators of obesity and hyperuricemia. Our study aims to investigate whether BMI-related gut microbiota characteristics would mediate the association between BMI and SUA levels. A total of 6,280 participants from Guangdong Gut Microbiome Project were included in this study. Stool samples were collected for 16S rRNA gene sequencing. The results revealed that BMI was significantly and positively associated with SUA. Meanwhile, BMI was significantly associated with the abundance of 102 gut microbial genera, 16 of which were also significantly associated with SUA. The mediation analysis revealed that the association between BMI and SUA was partially mediated by the abundance of Proteobacteria (proportion mediated: 0.94%, P < 0.05). At the genus level, 25 bacterial genera, including Ralstonia, Oscillospira, Faecalibacterium, etc., could also partially mediate the association of BMI with SUA (the highest proportion is mediated by Ralstonia, proportion mediated: 2.76%, P < 0.05). This study provided evidence for the associations among BMI, gut microbiota, and SUA, and the mediation analysis suggested that the association of BMI with SUA was partially mediated by the gut microbiota. IMPORTANCE Using 16S rRNA sequencing analysis, local interpretable machine learning technique analysis and mediation analysis were used to explore the association between BMI with SUA, and the mediating effects of gut microbial dysbiosis in the association were investigated.

Singer recognition plays a vital role in music information retrieval systems. Most songs in the singer recognition system are mixed audios of music and voice. In contrast, there is a lack of labeled a cappella solo singing data suitable for singer recognition. Text-independent singer recognition systems successfully encode audio features such as voice pitch, intensity, and timbre to achieve good performance. Most such systems are trained and evaluated using data from music with accompaniment. However, due to the influence of background music, the performance of the singer recognition model was limited. Contrarily, a powerful singer identification system can be trained and evaluated using a cappella solo singing voice with a clear and broad range of qualities. There needs to be labeled clear singing data suitable for singer recognition research. To address this issue, we present Vocal92, a multivariate a cappella solo singing and speech audio dataset spanning around 146.73 hours sourced from volunteers. Furthermore, we use three models to construct the singer recognition baseline system. In experiments, the singer recognition model developed by a cappella solo singing data performs well in both single-mode and cross-modal verification data, significantly improving related works. The dataset is accessible to everyone at https://pan.baidu.com/s/1Pn62DHfal2OOZ_5JqgGBdQ with jnz5 as the validation code. For non-commercial use, the dataset is available free of charge at the IEEE DataPort (https://ieee-dataport.org/documents/vocal92-multimodal-audio-dataset-cappella-solo-singing-and-speech).

Abstract Background Plant and animal embryogenesis have conserved and distinct features. Cell fate transitions occur during embryogenesis in both plants and animals. The epigenomic processes regulating plant embryogenesis remain largely elusive. Results Here, we elucidate chromatin and transcriptomic dynamics during embryogenesis of the most cultivated crop, hexaploid wheat. Time-series analysis reveals stage-specific and proximal–distal distinct chromatin accessibility and dynamics concordant with transcriptome changes. Following fertilization, the remodeling kinetics of H3K4me3, H3K27ac, and H3K27me3 differ from that in mammals, highlighting considerable species-specific epigenomic dynamics during zygotic genome activation. Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 deposition is important for embryo establishment. Later H3K27ac, H3K27me3, and chromatin accessibility undergo dramatic remodeling to establish a permissive chromatin environment facilitating the access of transcription factors to cis-elements for fate patterning. Embryonic maturation is characterized by increasing H3K27me3 and decreasing chromatin accessibility, which likely participates in restricting totipotency while preventing extensive organogenesis. Finally, epigenomic signatures are correlated with biased expression among homeolog triads and divergent expression after polyploidization, revealing an epigenomic contributor to subgenome diversification in an allohexaploid genome. Conclusions Collectively, we present an invaluable resource for comparative and mechanistic analysis of the epigenomic regulation of crop embryogenesis.

Abstract As the lastly unexplored electromagnetic wave, terahertz (THz) radiation has been exploited in a plenty of contexts such as fundamental research, military and civil fields. Most recently, representative two‐dimensional (2D) topological semimetal, platinum ditelluride (PtTe2) has attracted considerable research interest in THz detection due to its unique physical properties. However, to achieve practical applications, the low‐cost, large‐scale, controllable synthesis and efficient patterning of 2D materials are key requirements, which remain a challenge for PtTe2 and its photodetectors (PDs). Herein, a facile approach is developed to obtain wafer‐scale (2‐inches) patterned PtTe2 arrays using one‐step tellurium‐vapor transformation method and micro‐Nano technology. PtTe2 PD arrays are fabricated with the as‐grown PtTe2 arrays evenly distributed on a 2‐inch wafer, exhibiting high conductivity (~2.7 × 105 S m−1) and good electrical consistency. Driven by the Dirac fermions, PtTe2 PDs achieve a broadband (0.02–0.3 THz) response with a fast response speed (~4.7 μs), a high sensitivity (~47 pW Hz−1/2) and high‐resolution transmission THz‐imaging capability, which displays the potential of large‐area THz array imaging. These results are one step towards the practical applications of integrated PD arrays based on 2D materials.

Abstract Background The emergence of antimicrobial resistance has necessitated the development of effective alternatives to antibiotics for livestock and poultry production. This study investigated a possible synergy between butyrate and forskolin (a natural labdane diterpene) in enhancing innate host defense, barrier function, disease resistance, growth performance, and meat quality of broilers. Methods The expressions of representative genes involved in host defense (AvBD9 and AvBD10), barrier function (MUC2, CLDN1, and TJP1), and inflammation (IL-1β) were measured in chicken HD11 macrophages in response to butyrate and forskolin in the presence or absence of bacterial lipopolysaccharides (LPS). Intestinal lesions and the Clostridium perfringens titers were also assessed in C. perfringens-challenged chickens fed butyrate and forskolin-containing Coleus forskohlii (CF) extract individually or in combination. Furthermore, growth performance and carcass characteristics were evaluated in broilers supplemented with butyrate and the CF extract for 42 d. Results Butyrate and forskolin synergistically induced the expressions of AvBD9, AvBD10, and MUC2 in chicken HD11 cells (P

A new algorithm is proposed to solve the problems of shape-finding of suspension bridge with spatial cables what include tedious iteration, slow convergence speed and even no convergent under some circumstances. In this paper, the stress analysis of the main cable is carried out, and the relationship between the slope change and the coordinate change is found. This paper also discussed how to find the minimum slope point of symmetrical or asymmetric main cable, and the deformation compatibility equation is established and solved to obtain the shape of main cable. The algorithm in this paper can ensure the convergence of the solution for the suspension bridge with spatial cables. The calculation accuracy is high through the demonstration of the calculation examples.

Abstract Despite the interest toward the terahertz (THz) rapidly increasing, the high‐efficient detection of THz photon is not widely available due to the low photoelectric conversion efficiency at this low‐energy photon regime. Excitonic insulator (EI) states in emerging materials with anomalous optical transitions and renormalized valence band dispersions render their nontrivial photoresponse, which offers the prospect of harnessing the novel EI properties for the THz detection. Here, an EI‐based photodetector is developed for efficient photoelectric conversion in the THz band. High‐quality EI material Ta2NiSe5 is synthesized and the existence of the EI state at room temperature is confirmed. The THz scanning near‐field optical microscopy experimentally reveals the strong light–matter interaction in the THz band of EI state in the Ta2NiSe5. Benefiting from the strong light–matter interaction, the Ta2NiSe5‐based photodetectors exhibit superior THz detection performances with a detection sensitivity of ≈42 pW Hz−1/2 and a response time of ≈1.1 µs at 0.1 THz at room temperature. This study provides a new avenue for realizing novel high‐performance THz photodetectors by exploiting the emerging EI materials.

The antioxidant enzyme system is the main defense system responsible for maintaining cellular reactive oxygen species (ROS) homeostasis and normal plant growth and development after saline stress. In this study, we identified and characterized the members of the SOD, APX and CAT gene families of the antioxidant enzyme system in Gymnocarpos przewalskii, using plant physiology and molecular biology methods, and analyzed the pattern of enzyme activity in response to NaCl stress. It was found that seven, six and two genes of SOD, APX and CAT gene families, respectively, were expressed in the leaf tissue of G. przewalskii, in which most of the genes were significantly upregulated under NaCl stress, and the enzymatic activities were in accordance with the gene expression. Three positive selection sites in the GpCAT1 gene can increase the hydrophilicity of the GpCAT1 protein, increase the volume of the active site and increase the affinity for H2O2, thus improving the catalytic efficiency of GpCAT1. The results of the present study provide new insights for further investigations of the evolution and function of the SOD, APX and CAT gene families in G. przewalskii and their essential roles under salt stress, and the findings will be useful for revealing the molecular mechanism of salt tolerance and breeding of salt-tolerant plants.

Parabacteroides levels are reported to be low in obese individuals, and this genus has shown an anti-obesity capacity in animal studies. Nevertheless, the relationship between Parabacteroides and obesity in different subpopulations, e.g., with respect to age and sex, and its association with subsequent weight change have rarely been explored. The cross-sectional associations of Parabacteroides genus- and species-level OTU abundance with obesity were explored in the Guangdong Gut Microbiome Project (GGMP), which included 5843 adults, and replicated in the Guangzhou Nutrition and Health Study (GNSH), which included 1637 individuals. Furthermore, we assessed the prospective associations of Parabacteroides and its main OTUs’ abundance with the subsequent changes in body mass index (BMI) in the GNSH. We found that Parabacteroides was inversely associated with obesity among females and participants aged 40–69 years in the GGMP and the replicated cohort in the GNSH. After a 3-year follow-up, there was no significant correlation between Parabacteroides and the subsequent changes in BMI. However, Seq4172 (P. johnsonii) showed a negative correlation with subsequent BMI changes in the female and middle-aged (40–69 years) subpopulations. Overall, our results indicate that Parabacteroides have an inverse relationship with obesity and that Seq4172 (P. johnsonii) have a negative association with subsequent changes in BMI among females and middle-aged populations in perspective analyses.

The plant compact and dwarf growth habit is an important agronomic trait when breeding watermelon (Citrullus lanatus) cultivars because of their reduced vine length, high-density planting, and better land utilization; however, the genetic basis of the dwarf growth habit is not well-known. In this study, the plant population of six generations, P1, P2, F1, F2, BC1P1, and BC1P2, were studied. A genetic segregation analysis demonstrated that dwarfism is mainly controlled by a single recessive Cldw gene. Furthermore, whole-genome sequencing of two distinct watermelon cultivars, W1-1 (P1) and 812 (P2), was performed and preliminarily mapped through a bulked segregant analysis of F2 individuals that revealed the Cldw gene locus on chromosome 9. Two candidate genes, Cla015407 and Cla015408, were discovered at the delimited region of 43.2 kb by fine mapping, and gene annotation exposed that the Cla015407 gene encodes gibberellic acid 3β-hydroxylase protein. In addition, a comparative analysis of gene sequence and cultivars sequences across the reference genome of watermelon revealed the splice site mutation in the intron region of the Cldw gene in dwarf-type cultivar 812. The quantitative real-time polymerase chain reaction exhibited a significantly higher expression of the Cla015407 gene in cultivar W1-1 compared with 812. There was no significant difference in the vine length of both cultivars after gibberellic acid treatment. In brief, our fine mapping demonstrated that Cla015407 is a candidate gene controlling dwarfism of watermelon plants.

Abstract Elucidating the chromatin dynamics that orchestrate embryogenesis is a fundamental question in developmental biology. Here, we exploit position effects on expression as an indicator of chromatin activity and infer the chromatin activity landscape in every lineaged cell during Caenorhabditis elegans early embryogenesis. Systems‐level analyses reveal that chromatin activity distinguishes cellular states and correlates with fate patterning in the early embryos. As cell lineage unfolds, chromatin activity diversifies in a lineage‐dependent manner, with switch‐like changes accompanying anterior–posterior fate asymmetry and characteristic landscapes being established in different cell lineages. Upon tissue differentiation, cellular chromatin from distinct lineages converges according to tissue types but retains stable memories of lineage history, contributing to intra‐tissue cell heterogeneity. However, the chromatin landscapes of cells organized in a left–right symmetric pattern are predetermined to be analogous in early progenitors so as to pre‐set equivalent states. Finally, genome‐wide analysis identifies many regions exhibiting concordant chromatin activity changes that mediate the co‐regulation of functionally related genes during differentiation. Collectively, our study reveals the developmental and genomic dynamics of chromatin activity at the single‐cell level.

In the past 20 years, patients with rheumatoid arthritis (RA), Crohn's disease (CD), and other immune diseases have witnessed the impact of a great treatment advance with the availability of biological TNFα inhibitors. With 5 approved anti-TNFα biologics on the market and soon available biosimilars, patients have more treatment options and have benefited from understanding the biology of TNFα. Nevertheless, many unmet needs remain for people living with TNFα-related diseases, namely some side effects and tolerance of current anti-TNFα biologics and resistance to therapies. Furthermore, common diseases such as osteoarthritis and back/neck pain may respond to anti-TNFα therapies at early onset of symptoms. Development of new TNFα inhibitors focusing on TNFR1 specific inhibitors, preferably small molecules that can be delivered orally, is much needed.

High-performance InAs/GaSb type-II superlattice infrared detectors and focal plane arrays (FPAs) are normally grown by molecular beam epitaxy (MBE). In this work, we demonstrate the first long-wavelength infrared InAs/GaSb superlattice FPA grown by metalorganic chemical vapor deposition (MOCVD) with clear image. High-quality superlattice material was obtained evidenced by sharp X-ray diffraction peaks and atomic flat surface. Electrical and optical measurements performed on single element detectors showed a 50% cut-off wavelength of $\sim 10.1~\mu \text{m}$ , a dark current density of $2.5\times 10^{-5}$ A/cm2, a peak responsivity of 0.88 A/W and a peak detectivity of $1.7\times 10^{11}$ cm $\cdot $ Hz1/2/W at 80 K. A $320\times256$ FPA with $30~\mu \text{m}$ pixel pitch was then fabricated. With an integration time of 1.9 ms and an applied bias of -0.1 V, the FPA shows an average operability of 96.96%, a non-uniformity of 4.97%, a noise equivalent temperature difference of 51.1 mK and a peak detectivity of $2.3\times 10^{10}$ cm $\cdot $ Hz1/2/W at 80 K without thinning down the substrate.

Abstract During plant evolution, there is genetic communication between organelle and nuclear genomes. A comparative analysis was performed on the organelle and nuclear genomes of the watermelon and melon. In the watermelon, chloroplast-derived sequences accounted for 7.6% of the total length of the mitochondrial genome. In the melon, chloroplast-derived sequences accounted for approximately 2.73% of the total mitochondrial genome. In watermelon and melon, the chloroplast-derived small-fragment sequences are either a subset of large-fragment sequences or appeared multiple times in the mitochondrial genome, indicating that these fragments may have undergone multiple independent migration integrations or emerged in the mitochondrial genome after migration, replication, and reorganization. There was no evidence of migration from the mitochondria to chloroplast genome. A sequence with a total length of about 73 kb (47%) in the watermelon chloroplast genome was homologous to a sequence of about 313 kb in the nuclear genome. About 33% of sequences in the watermelon mitochondrial genome was homologous with a 260 kb sequence in the nuclear genome. A sequence with a total length of about 38 kb (25%) in the melon chloroplast genome was homologous with 461 sequences in the nuclear genome, with a total length of about 301 kb. A 3.4 Mb sequence in the nuclear genome was homologous with a melon mitochondrial sequence. These results indicate that, during the evolution of watermelon and melon, a large amount of genetic material was exchanged between the nuclear genome and the two organelle genomes in the cytoplasm.

Wetland health assessment provides important basis for wetland restoration and management. However, it is quite tricky to select proper indicators from multiple assessment indicators that can truly reflect the health state of urban wetlands. In an attempt to address these problems, a pressure-state-response (PSR) and back propagation artificial neural network (BP) conjoined model was established for health assessment of several plateau urban wetlands in Xining City, China. The model was driven and verified through field monitoring and social questionnaire data for 4 consecutive years from 2016 to 2019. Results indicate that: (1) Eight health evaluation indexes, including population density, eutrophication level, increasing humidity, carbon dioxide absorption, air purifying, recreation, wetland management level and investment in ecological construction and protection were selected from 45 input indexes. (2) The health index of Huangshui National Wetland Park has been increasing year by year, with an average of comprehensive health score of 0.746, 0.790, 0.884, and 0.877, respectively. The indicators that contributed the most to the restoration effect were leisure and entertainment service value (2016), carbon dioxide absorption service value (2017), eutrophication (2018), and wetland management level (2019), respecially. (3) Compared with the single PSR method, the advantages of this method include; There are fewer evaluation indicators, more accurate results (excluding the interference of some highly variable indicators) and more sensitive to environmental changes. The current study proposed a novel method that may provide additional accurate and refined indicators for urban wetland health assessment.

With the development of society, big data's concept is mentioned more and more. However, in the numerous and complex mass data, the effective information is often very limited, and the data often show the complex characteristics of "close and orderly short-term correlation and large long-term disturbance", which is difficult to be expressed by a long sequence composed of a single real value. This paper takes the interval grey number as the research object for the uncertain system of "less data and poor information". According to the multi-attribute group decisions problem with attribute’s values of interval grey number and the weights of decision-makers and attributes that are completely unknown, a method of group decision making with interval grey numbers based on grey correlation and relative close degree is proposed. For the purpose of making effective decisions, the weights of decision-makers and attributes are calculated by correlation degree of decision information which is measured by the model of grey correlation analysis based on interval grey number deviation degree. On this basis, the correlation degree between the scheme and the positive and negative ideal schemes are computed, and then the grey correlation and relative close degree of the scheme is calculated. Finally, the scheme is sorted according to the value of the grey correlation and relative close degree. The rationality and feasibility of the proposed method are verified by numerical examples.