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Abstract During the progression of proliferative vitreoretinopathy (PVR) following ocular trauma, previously quiescent retinal pigment epithelial (RPE) cells transition into a state of rapid proliferation, migration, and secretion. The elusive molecular mechanisms behind these changes have hindered the development of effective pharmacological treatments, presenting a pressing clinical challenge. In this study, by monitoring the dynamic changes in chromatin accessibility and various histone modifications, we chart the comprehensive epigenetic landscape of RPE cells in male mice subjected to traumatic PVR. Coupled with transcriptomic analysis, we reveal a robust correlation between enhancer activation and the upregulation of the PVR-associated gene programs. Furthermore, by constructing transcription factor regulatory networks, we identify the aberrant activation of enhancer-driven RANK-NFATc1 pathway as PVR advanced. Importantly, we demonstrate that intraocular interventions, including nanomedicines inhibiting enhancer activity, gene therapies targeting NFATc1 and antibody therapeutics against RANK pathway, effectively mitigate PVR progression. Together, our findings elucidate the epigenetic basis underlying the activation of PVR-associated genes during RPE cell fate transitions and offer promising therapeutic avenues targeting epigenetic modulation and the RANK-NFATc1 axis for PVR management.

Modern suspension bridges exhibit a trend of lighter structures, more diversified structural forms, and longer spans, the latter already exceeding two kilometers. Bridge performance under dead and live loads depends on their structural and main cable systems, while cable-supported bridges especially rely on the design analysis and construction control of the main cable. This literary survey systematically analyzes the research progress and state-of-the-art status quo in the structural systems and design theories of suspension bridges, focusing on the structural systems, main cable shape analyses, live load effect analyses, and emerging lucrative research directions. More than 100 reliable references have been surveyed. (1) Multi-span or multi-main cable schemes appeal to increasing attention, which may become a better choice in terms of structural systems in scenarios with extremely long spans and heavy loads. The cable layouts, such as spatial main cables and hybrid cable-stayed suspension systems have also become feasible approaches for enhancing structural stiffness. (2) The shape-finding analysis during the construction phase is more complex and has more essential factors than that of the completed bridge state. Refined theories combining analytical methods and finite element methods are more suitable for the shape-finding analysis of complex cable systems than any single theory of the two, especially for novel cable systems. (3) The live load effect analysis methods based on traditional deflection theory or modified/improved deflection theories still have wide applications, but the refined theory of treating hangers as discrete members is also constantly developing, which is expected to provide new ideas for more complex structural analysis under the different types of live loads and their distribution forms.

Abstract Chondrocyte senescence and reduced lubrication play pivotal roles in the pathogenesis of age‐related osteoarthritis (OA). In the present study, highly lubricated and drug‐loaded hydrogel microspheres are designed and fabricated through the radical polymerization of sulfobetaine (SB)‐modified hyaluronic acid methacrylate using microfluidic technology. The copolymer contains a large number of SB and carboxyl groups that can provide a high degree of lubrication through hydration and form electrostatic loading interactions with metformin (Met@SBHA), producing a high drug load for anti‐chondrocyte senescence. Mechanical, tribological, and drug release analyses demonstrated enhanced lubricative properties and prolonged drug dissemination of the Met@SBHA microspheres. RNA sequencing (RNA‐seq) analysis, network pharmacology, and in vitro assays revealed the extraordinary capacity of Met@SBHA to combat chondrocyte senescence. Additionally, inducible nitric oxide synthase (iNOS) has been identified as a promising protein modulated by Met in senescent chondrocytes, thereby exerting a significant influence on the iNOS/ONOO‐/P53 pathway. Notably, the intra‐articular administration of Met@SBHA in aged mice ameliorated cartilage senescence and OA pathogenesis. Based on the findings of this study, Met@SBHA emerges as an innovative and promising strategy in tackling age‐related OA serving the dual function of enhancing joint lubrication and mitigating cartilage senescence.

Purpose This investigation aims to explore the protective role of Naringenin (Nar) in bone cancer pain (BCP) via TNF-α-mediated NF-κB/uPA/PAR2 pathway. Methods BCP model was manipulated by the injection of LL2 cells into femur of mice. The levels of TNF-α and uPA in bone tissue and serum were studied by ELISA. The expressions of PAR2, PKC-γ, PKA and TRPV1 were determined by qPCR and western blot. Levels of p-IKKβ, IKKβ, p-p65, p65 were determined by western blot. Levels of p-p65 and uPA in bone tissue were studied by immunohistochemistry. Behavior tests in this investigation included paw withdrawal latency (PWL) and the paw withdrawal threshold (PWT). Radiological analysis and micro-CT were used to study bone structure. The lesions of bone tissue were determined by HE staining. The Dorsal root ganglia (DRG) isolated from mice were used to determine the level of PAR2 pathway. Results Naringenin improved the BCP-induced bone damage based on the increases of BV/TV, Conn. D, BMD and BMC and the decrease of bone destruction score. Naringenin repressed the reductions of PWT and PWL in BCP mice. Naringenin decreased the levels of PAR2, PKC-γ, PKA and TRPV1 of DRG and reduced the levels of p-IKKβ, p-p65, and uPA in serum and bone tissue in BCP. Importantly, naringenin suppressed the enhancement of TNF-α in serum and bone tissue in BCP mice. Conclusion Naringenin alleviated pain sensitization and bone damage of mice with BCP via TNF-α-mediated NF-κB/uPA/PAR2 pathway. We demonstrated a novel pathway for anti-BCP treatment with naringenin.

Abstract Lithium‐ion batteries (LIBs) are currently the predominant energy storage power source. However, the urgent issues of enhancing electrochemical performance, prolonging lifetime, preventing thermal runaway‐caused fires, and intelligent application are obstacles to their applications. Herein, bio‐inspired electrodes owning spatiotemporal management of self‐healing, fast ion transport, fire‐extinguishing, thermoresponsive switching, recycling, and flexibility are overviewed comprehensively, showing great promising potentials in practical application due to the significantly enhanced durability and thermal safety of LIBs. Taking advantage of the self‐healing core–shell structures, binders, capsules, or liquid metal alloys, these electrodes can maintain the mechanical integrity during the lithiation–delithiation cycling. After the incorporation of fire‐extinguishing binders, current collectors, or capsules, flame retardants can be released spatiotemporally during thermal runaway to ensure safety. Thermoresponsive switching electrodes are also constructed though adding thermally responsive components, which can rapidly switch LIB off under abnormal conditions and resume their functions quickly when normal operating conditions return. Finally, the challenges of bio‐inspired electrode designs are presented to optimize the spatiotemporal management of LIBs. It is anticipated that the proposed electrodes with spatiotemporal management will not only promote industrial application, but also strengthen the fundamental research of bionics in energy storage.

Summary: Hypoxia promotes tumorigenesis and lactate accumulation in esophageal squamous cell carcinoma (ESCC). Lactate can induce histone lysine lactylation (Kla, a recently identified histone marks) to regulate transcription. However, the functional consequence of histone Kla under hypoxia in ESCC remains to be explored. Here, we reveal that hypoxia facilitates histone H3K9la to enhance LAMC2 transcription for proliferation of ESCC. We found that global level of Kla was elevated under hypoxia, and thus identified the landscape of histone Kla in ESCC by quantitative proteomics. Furthermore, we show a significant increase of H3K9la level induced by hypoxia. Next, MNase ChIP-seq and RNA-seq analysis suggest that H3K9la is enriched at the promoter of cell junction genes. Finally, we demonstrate that the histone H3K9la facilitates the expression of LAMC2 for ESCC invasion by in vivo and in vitro experiments. Briefly, our study reveals a vital role of histone Kla triggered by hypoxia in cancer.

Summary: Background: Limited knowledge exists regarding behavioral and biomarker shifts during the period from respiratory infection exposure to testing decisions (the diagnostic decision period), a key phase affecting transmission dynamics and public health strategy development. This study aims to examine the changes in behavior and biomarkers during the diagnostic decision period for COVID-19, influenza, and group A streptococcus (GAS). Methods: We analyzed data from a two-year prospective cohort study involving 4795 participants in Israel, incorporating smartwatch data, self-reported symptoms, and medical records. Our analysis focused on three critical phases: the digital incubation period (from exposure to physiological anomalies detected by smartwatches), the symptomatic incubation period (from exposure to onset of symptoms), and the diagnostic decision period for influenza, COVID-19, and GAS. Findings: The delay between initial symptom reporting and testing was 39 [95% confidence interval (CI): 34–45] hours for influenza, 53 [95% CI: 49–58] hours for COVID-19, and 38 [95% CI: 32–46] hours for GAS, with 73 [95% CI: 67–78] hours from anomalies in heart measures to symptom onset for influenza, 23 [95% CI: 18–27] hours for COVID-19, and 62 [95% CI: 54–68] hours for GAS. Analyzing the entire course of infection of each individual, the greatest changes in heart rates were detected 67.6 [95% CI: 62.8–72.5] hours prior to testing for influenza, 64.1 [95% CI: 61.4–66.7] hours prior for COVID-19, and 58.2 [95% CI: 52.1–64.2] hours prior for GAS. In contrast, the greatest reduction in physical activities and social contacts occurred after testing. Interpretation: These findings highlight the delayed response of patients in seeking medical attention and reducing social contacts and demonstrate the transformative potential of smartwatches for identifying infection and enabling timely public health interventions. Funding: This work was supported by the European Research Council, project #949850, the Israel Science Foundation (ISF), grant No. 3409/19, within the Israel Precision Medicine Partnership program, and a Koret Foundation gift for Smart Cities and Digital Living.

The ground disturbance caused by the tunnel construction will inevitably have an impact on the upper part of the constructed tunnel structure, and the railroad tunnel requires a very high level of control over the structural settlement deformation. For the problem of double-hole tunnel under the built tunnel, this paper takes Chongqing Mingyue Mountain Tunnel under the built Shanghai-Rong Railway Paihua Cave tunnel and Zheng-Yu Railway tunnel as the engineering background, and starts from the mechanism of ground loss caused by tunnel excavation, firstly, the settlement at the height of the existing tunnel strata is obtained through theoretical analysis, and the new Mingyue Mountain Tunnel under the Shanghai-Rong Railway tunnel is determined to be a more dangerous section. Further simulate and calculate the dynamic excavation process of the new double-hole tunnel underpass, and study the settlement deformation law of the Mingyue Mountain Tunnel underpassing the Hurong Railway Tunnel. According to the requirements of railroad tunnel for settlement deformation control, the new tunnel is determined to be constructed by step method to ensure the safety of railroad tunnel. The shortcomings of the theoretical calculation are analyzed to illustrate the important role of numerical simulation in the evaluation of tunnel underpass projects.

It is well acknowledged to all that an active equalization strategy can overcome the inconsistency of lithium-ion cell's voltage and state of charge (SOC) in series-connected lithium-ion battery (LIB) pack in the electric vehicle application. In this regard, a novel dual threshold trigger mechanism based active equalization strategy (DTTM-based AES) is proposed to overcome the inherent inconsistency of cells and to improve the equalization efficiency for a series-connected LIB pack. First, a modified dual-layer inductor equalization circuit is constructed to make it possible for the energy transfer path optimization. Next, based on the designed dual threshold trigger mechanism provoked by battery voltage and SOC, an active equalization strategy is proposed, each single cell's SOC in the battery packs is estimated using the extended Kalman particle filter algorithm. Besides, on the basis of the modified equalization circuit, the improved particle swarm optimization is adopted to optimize the energy transfer path with aiming to reduce the equalization time. Lastly, the simulation and experimental results are provided to validate the proposed DTTM-based AES.

This review provides a comprehensive analysis of the critical role played by macrophages and their underlying mechanisms in the progression of diabetic cardiomyopathy (DCM). It begins by discussing the origins and diverse subtypes of macrophages, elucidating their spatial distribution and modes of intercellular communication, thereby emphasizing their significance in the pathogenesis of DCM. The review then delves into the intricate relationship between macrophages and the onset of DCM, particularly focusing on the epigenetic regulatory mechanisms employed by macrophages in the context of DCM condition. Additionally, the review discusses various therapeutic strategies aimed at targeting macrophages to manage DCM. It specifically highlights the potential of natural food components in alleviating diabetic microvascular complications and examines the modulatory effects of existing hypoglycemic drugs on macrophage activity. These findings, summarized in this review, not only provide fresh insights into the role of macrophages in diabetic microvascular complications but also offer valuable guidance for future therapeutic research and interventions in this field.

Abstract Background Immunoglobulin lambda (Igλ) has been reported to be expressed in many normal and tumor tissues and cells. However, the function and clinical significance of tumor-derived Igλ remain unclear. Methods The differential expressions of Immunoglobulin Lambda Constants (IGLCs) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) were examined with The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) databases. The effects of IGLCs on patient clinical phenotypes and prognosis were explored via bioinformatics analyses based on the TCGA databases. We used the bioinformatics analyses based on the TCGA and GTEx databases to elucidate the correlations among IGLC expressions, immunomodulator expressions, tumor stemness, and infiltration scores of tumor infiltrating immune cells. Co-immunoprecipitation (Co-IP) and silver staining combined with liquid chromatography-tandem mass spectrometry (LC–MS/MS) were used to obtain potential tumor-derived Igλ-interacting proteins. Functional annotation of candidate proteins identified by LC–MS/MS was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The bioinformatics analyses of 7 IGLCs in CESC and normal cervical tissues were performed based on TCGA, GTEx, and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases. Protein–protein interaction (PPI) network was analyzed based on tumor-derived Igλ-interacting proteins in Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Immunohistochemistry (IHC) was used to validate the expressions of IGLCs in CESC. Results We found that the expressions of the majority of IGLCs (IGLC1, IGLC2, IGLC3, IGLC4, IGLC5, IGLC6, and IGLC7) were upregulated in CESC tissues, compared with those in normal cervical tissues. The expressions of IGLC5 and IGLC7 had significant difference in different pathologic metastasis (M), one of tumor, node, and metastasis (TNM) staging system, categories of CESC. Except for disease-free interval (DFI), 4 IGLC (IGLC1, IGLC2, IGLC3, and IGLC7) expression levels were positively associated with patient overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) respectively in CESC tissues. 5 IGLC (IGLC1, IGLC2, IGLC3, IGLC6, and IGLC7) expressions were positively correlated with the expressions of a majority of immunomodulators respectively in CESC tissues. Tumor stemness was negatively correlated with the expressions of 4 IGLCs (IGLC1, IGLC2, IGLC3, and IGLC7) respectively in CESC tissues. Except for IGLC4, IGLC5, and IGLC7, 4 IGLC (IGLC1, IGLC2, IGLC3, and IGLC6) expressions were positively correlated with infiltration scores of 6 tumor-infiltrating immune cells (B cell, T cell CD4, T cell CD8, neutrophil, macrophage, and DC). After analyses of the above bioinformatics data of tumor-derived Igλ, Co-IP and LC–MS/MS were used to confirm that 4 proteins (RPL7, RPS3, H1-5, and H1-6) might interact with tumor-derived Igλ in cervical cancer cells. Functional analyses of these candidate proteins showed that they interacted with many proteins and were involved in various cellular biological processes. Finally, IHC was used to further confirm the above bioinformatics results, it was indicated that the expression level of Igλ in cervical adenocarcinoma and cervical squamous cell carcinoma was higher than that in normal cervical tissue. Conclusion This study comprehensively investigated the functions of tumor-derived Igλ and its interacting proteins based on bioinformatics analysis and the potential value of Igλ as a prognostic and therapeutic marker for CESC, providing new direction and evidence for CESC therapy.

We report accretion-powered pulsations for the first time during thermonuclear bursts in hard X-rays, which were observed with Insight-HXMT in 2022 during the outburst of the accreting X-ray millisecond pulsar MAXI J1816-195. By stacking 73 bursts, we detected pulse profiles in 8–30 and 30–100 keV during bursts, which are identical to those obtained from the persistent (nonburst) emission. On average, no significant phase lag was observed between burst and persistent pulse profiles. In addition, we suggest that the interaction with burst photons can be used as a direct diagnostic to distinguish contributions from the hot plasma near polar caps and the corona around the accretion disk, which are highly degenerate in their spectral shapes.

BackgroundInflammation is the common pathogenesis of coronary atherosclerosis disease (CAD) and rheumatoid arthritis (RA). Although it is established that RA increases the risk of CAD, the underlining mechanism remained indefinite. This study seeks to explore the molecular mechanisms of RA linked CAD and identify potential target gene for early prediction of CAD in RA patients.Materials and methodsThe study utilized five raw datasets: GSE55235, GSE55457, GSE12021 for RA patients, and GSE42148 and GSE20680 for CAD patients. Gene Set Enrichment Analysis (GSEA) was used to investigate common signaling pathways associated with RA and CAD. Then, weighted gene co-expression network analysis (WGCNA) was performed on RA and CAD training datasets to identify gene modules related to single-sample GSEA (ssGSEA) scores. Overlapping module genes and differentially expressed genes (DEGs) were considered as co-susceptible genes for both diseases. Three hub genes were screened using a protein-protein interaction (PPI) network analysis via Cytoscape plug-ins. The signaling pathways, immune infiltration, and transcription factors associated with these hub genes were analyzed to explore the underlying mechanism connecting both diseases. Immunohistochemistry and qRT-PCR were conducted to validate the expression of the key candidate gene, PPARG, in macrophages of synovial tissue and arterial walls from RA and CAD patients.ResultsThe study found that Fc-gamma receptor-mediated endocytosis is a common signaling pathway for both RA and CAD. A total of 25 genes were screened by WGCNA and DEGs, which are involved in inflammation-related ligand-receptor interactions, cytoskeleton, and endocytosis signaling pathways. The principal component analysis(PCA) and support vector machine (SVM) and receiver-operator characteristic (ROC) analysis demonstrate that 25 DEGs can effectively distinguish RA and CAD groups from normal groups. Three hub genes TUBB2A, FKBP5, and PPARG were further identified by the Cytoscape software. Both FKBP5 and PPARG were downregulated in synovial tissue of RA and upregulated in the peripheral blood of CAD patients and differential mRNAexpreesion between normal and disease groups in both diseases were validated by qRT-PCR.Association of PPARG with monocyte was demonstrated across both training and validation datasets in CAD. PPARG expression is observed in control synovial epithelial cells and foamy macrophages of arterial walls, but was decreased in synovial epithelium of RA patients. Its expression in foamy macrophages of atherosclerotic vascular walls exhibits a positive correlation (r = 0.6276, p = 0.0002) with CD68.ConclusionOur findings suggest that PPARG may serve as a potentially predictive marker for CAD in RA patients, which provides new insights into the molecular mechanism underling RA linked CAD.

Janus base nanotubes are novel, self-assembled nanomaterials. Their original designs were inspired by DNA base pairs, and today a variety of chemistries has developed, distinguishing them as a new family of materials separate from DNA origami, carbon nanotubes, polymers, and lipids. This review article covers the principal examples of self-assembled Janus base nanotubes, which are driven by hydrogen-bond and π-π stacking interactions in aqueous environments. Specifically, self-complementary hydrogen bonds organize molecules into ordered arrays, forming macrocycles, while π-π interactions stack these structures to create tubular forms. This review elucidates the molecular interactions that govern the assembly of nanotubes and advances our understanding of nanoscale self-assembly in water.

Abstract Tumor-infiltrating immune cells and fibroblasts are significant components of the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC), and they participate in tumor progression as closely as tumor cells. However, the relationship between the features of the TME and patient outcomes and the interactions among TME components are still unclear. In this study, we evaluated the PDAC TME in terms of the quantity and location of cluster of differentiation (CD)4+ T cells, CD8+ T cells, macrophages, stromal maturity, and tumor-stroma ratio (TSR), as evaluated by immunohistochemical staining of serial whole-tissue sections from 116 patients with PDAC. The density of T cells and macrophages (mainly activated macrophages) was significantly higher at the invasive margins (IMs) than at the tumor center (TC). CD4+ T cells were significantly association with all the other tumor-associated immune cells (TAIs) including CD8, CD68 and CD206 positive cells. Tumors of the non-mature (intermediate and immature) stroma type harbored significantly more CD8+ T cells at the IMs and more CD68+ macrophages at the IMs and the TC. The density of CD4+, CD8+, and CD206+ cells at the TC; CD206+ cells at the IMs; and tumor-node-metastasis (TNM) staging were independent risk factors for patient outcomes, and the c-index of the risk nomogram for predicting the survival probability based on the TME features and TNM staging was 0.772 (95% confidence interval: 0.713–0.832). PDAC harbored a significantly immunosuppressive TME, of which the IMs were the hot zones for TAIs, while cells at the TC were more predictive of prognosis. Our results indicated that the model based on the features of the TME and TNM staging could predict patient outcomes.

Infrared multispectral imaging technology can achieve the long-distance, wide-ranging and fast detection of target gas, and has been widely used in the fields of dangerous-gas detection and environmental monitoring. However, due to the difficulty in acquiring background radiation as well as atmospheric disturbance and noise interference in the detection process, the quantitative detection of gas concentration has become a difficult problem to solve. Therefore, this paper proposes an inversion method for gas column concentration based on infrared multispectral imaging technology. Firstly, infrared background radiation images of the non-target gas absorption spectrum band were collected and converted into background radiation images of the target gas absorption spectrum band according to the dual-channel mapping relationship. Then, combined with the gas radiation images of the target gas absorption spectrum band, the column concentration distribution of the gas was obtained by using the measured calibration relationship between absorbance and column concentration. Experiments of gas detection in different environments were carried out, and the column concentration distribution of the target gas was inverted using this method; the results showed that the average relative error of the inversion of the gas column concentration was 4.84%, which enables the quantitative detection of gas column concentration in a complex environment.

Abstract Background Taohong Siwu Decoction (THSWD) is a widely used traditional Chinese medicine (TCM) prescription in the treatment of ischemic stroke. There are thousands of chemical components in THSWD. However, the key functional components are still poorly understood. This study aimed to construct a mathematical model for screening of active ingredients in TCM prescriptions and apply it to THSWD on ischemic stroke. Methods Botanical drugs and compounds in THSWD were acquired from multiple public TCM databases. All compounds were initially screened by ADMET properties. SEA, HitPick, and Swiss Target Prediction were used for target prediction of the filtered compounds. Ischemic stroke pathological genes were acquired from the DisGeNet database. The compound–target–pathogenic gene (C-T-P) network of THSWD was constructed and then optimized using the multiobjective optimization (MOO) algorithm. We calculated the cumulative target coverage score of each compound and screened the top compounds with 90% coverage. Finally, verification of the neuroprotective effect of these compounds was performed with the oxygen-glucose deprivation and reoxygenation (OGD/R) model. Results The optimized C-T-P network contains 167 compounds, 1,467 predicted targets, and 1,758 stroke pathological genes. And the MOO model showed better optimization performance than the degree model, closeness model, and betweenness model. Then, we calculated the cumulative target coverage score of the above compounds, and the cumulative effect of 39 compounds on pathogenic genes reached 90% of all compounds. Furthermore, the experimental results showed that decanoic acid, butylphthalide, chrysophanol, and sinapic acid significantly increased cell viability. Finally, the docking results showed the binding modes of these four compounds and their target proteins. Conclusion This study provides a methodological reference for the screening of potential therapeutic compounds of TCM. In addition, decanoic acid and sinapic acid screened from THSWD were found having potential neuroprotective effects first and verified with cell experiments, however, further in vitro and in vivo studies are needed to explore the precise mechanisms involved.

Background: The formation of biomolecular condensates via phase separation has emerged as a fundamental principle underlying the spatiotemporal coordination of biological activities in cells. Aberrant biomolecular condensates often directly regulate key cellular process involved in the pathogenesis of human diseases, including kidney diseases. Summary: In this review, we summarize the physiological roles of phase separation and methodologies for phase separation studies. Taking autosomal dominant polycystic kidney disease as an example, we discuss recent advances toward elucidating the multiple mechanisms involved in kidney pathology arising from aberrant phase separation. We suggest that dysregulation of phase separation contributes to the pathogenesis of other important kidney diseases, including kidney injury and fibrosis. Key Messages: Phase separation provides a useful new concept to understand the mechanisms underlying kidney disease development. Targeting aberrant phase-separated condensates offers new therapeutic avenues for combating kidney diseases.

Abstract Background Lung cancer is a malignant tumour with the fastest increase in morbidity and mortality around the world. The clinical treatments available have significant side effects, thus it is desirable to identify alternative modalities to treat lung cancer. Shashen Maidong decoction (SMD) is a commonly used traditional Chinese medicine (TCM) formula for treating lung cancer in the clinic. While the key functional components (KFC) and the underlying mechanisms of SMD treating lung cancer are still unclear. Methods We propose a new integrated pharmacology model, which combines a novel node-importance calculation method and the contribution decision rate (CDR) model, to identify the KFC of SMD and to deduce their mechanisms in the treatment of lung cancer. Results The enriched effective Gene Ontology (GO) terms selected from our proposed node importance detection method could cover 97.66% of enriched GO terms of reference targets. After calculating CDR of active components in key functional network, the first 82 components covered 90.25% of the network information, which were defined as KFC. 82 KFC were subjected to functional analysis and experimental validation. 5–40 μM protocatechuic acid, 100–400 μM paeonol or caffeic acid exerted significant inhibitory activity on the proliferation of A549 cells. The results show that KFC play an important therapeutic role in the treatment of lung cancer by targeting Ras, AKT, IKK, Raf1, MEK, and NF-κB in the PI3K-Akt, MAPK, SCLC, and NSCLC signaling pathways active in lung cancer. Conclusions This study provides a methodological reference for the optimization and secondary development of TCM formulas. The strategy proposed in this study can be used to identify key compounds in the complex network and provides an operable test range for subsequent experimental verification, which greatly reduces the experimental workload.

Abstract The persistent dysregulation and accumulation of poisonous proteins from destructive neural tissues and cells activate pathological mechanisms after traumatic brain injury (TBI). The lymphatic drainage system of the brain, composed of the glymphatic system and meningeal lymphatic vessels (MLVs), plays an essential role in the clearance of toxic waste after brain injury. The neuroprotective effect of interleukin 33 (IL-33) in TBI mice has been demonstrated; however, its impact on brain lymphatic drainage is unclear. Here, we established a fluid percussion injury model to examine the IL-33 administration effects on neurological function and lymphatic drainage in the acute brain of TBI mice. We verified that exogenous IL-33 could improve the motor and memory skills of TBI mice and demonstrated that in the acute phase, it increased the exchange of cerebrospinal and interstitial fluid, reversed the dysregulation and depolarization of aquaporin-4 in the cortex and hippocampus, improved the drainage of MLVs to deep cervical lymph nodes, and reduced tau accumulation and glial activation. We speculate that the protective effect of exogenous IL-33 on TBI mice’s motor and cognitive functions is related to the enhancement of brain lymphatic drainage and toxic metabolite clearance from the cortex and hippocampus in the acute stage. These data further support the notion that IL-33 therapy may be an effective treatment strategy for alleviating acute brain injury after TBI.

In order to solve the problems of a low target recognition rate and poor real-time performance brought about by conventional infrared imaging spectral detection technology under complex background conditions or in the detection of targets of weak radiation or long distance, a kind of infrared polarization snapshot spectral imaging system (PSIFTIS) and a spectrum information processing method based on micro-optical devices are proposed in this paper, where the synchronous acquisition of polarization spectrum information is realized through the spatial modulation of phase with a rooftop-shaped multi-stage micro-mirror and the modulation of the polarization state of light with a micro-nanowire array. For the polarization interference image information obtained, the infrared polarization spectrum decoupling is realized by image segmentation, optical path difference matching, and image registration methods, the infrared polarization spectrum reconstruction is realized by Fourier transform spectral demodulation, and the infrared polarization image fusion is realized by decomposing and reconstructing the high- and low-frequency components of the polarization image based on the Haar wavelet transform. The maximum spectral peak wavenumber error of the four polarization channels of the polarization spectrum reconstruction is less than 2 cm−1, and the polarization angle error is within 1°. Ultimately, compared with the unprocessed polarization image unit, the peak signal-to-noise ratio is improved by 45.67%, the average gradient is improved by 8.03%, and the information entropy is improved by 56.98%.

Bactrocera dorsalis (Hendel) (B. dorsalis) is an important agricultural invasive pest that causes significant economic losses in tropical and subtropical fruit and vegetable crops. In this study, the proteins related to the sense of smell and taste of B. dorsalis, such as OBP, PBP, OR, IR, SNMP and CSP, were screened based on B. dorsalis transcriptome data. By integrating the compounds that were reported to be attractive to B. dorsalis, similar compounds of hydrocarbon compounds were obtained. Molecular docking was used to predict the binding between the similar compounds and the OBP, PBP, OR, IR, SNMP and CSP proteins. Network pharmacology was used to screen the potentially attractive compounds, and ecological experiments with B. dorsalis were finally conducted to verify the effect of these potentially attractive compounds on B. dorsalis. The results showed that the G protein-coupled receptor [BR: KO04030] and ion channel [BR: KO04040] pathways were closely related to the odor tropism of B. dorsalis. A total of 84 compounds, such as mitemcinal, exemestane and midecamycin, have potential binding effects on the B. dorsalis odor receptor proteins. The results of the ecological experiments showed that 1 mg/mL and 0.1 mg/mL 19-norandrostenedione, 1 mg/mL progesterone compounds was significantly attractive to B. dorsalis males, while 0.1 mg/mL exemestane was significantly attractive to B. dorsalis females. In this study, network pharmacology technology was used to discover the potential attractive compounds for B. dorsalis, which is important for the development and subsequent prevention and control of B. dorsalis. It can provide a reference in improving the success rates of clinical trials of new pest control products and in reducing the time and cost of drug development.

The use of a dual-interference channels static Fourier transform imaging spectrometer based on stepped micro-mirror (D-SIFTS) for environmental gas monitoring has the advantages of high throughput, a compact structure, and a stable performance. It also has the characteristics of both a broad spectral range and high spectral resolution. However, its unique structural features also bring many problems for subsequent data processing, mainly including the complex distribution of the interference data, the low signal-to-noise ratio (SNR) of infrared scene images, and a unique inversion process of material information. To this end, this paper proposes a method of image and spectra information processing and gas concentration inversion. A multiscale enhancement algorithm for infrared images incorporating wavelet denoising is used to obtain high-quality remote sensing scene images, and spectral reconstruction optimization algorithms, such as interference intensity sequence resampling, are used to obtain accurate spectral information; the quantitative calibration model of the detected gas concentration is established to achieve high-precision inversion of gas concentration, and its distribution is visualized in combination with the scene image. Finally, the effectiveness and accuracy of the data processing algorithm are verified through the use of several experiments, which provide essential theoretical guidance and technical support for the practical applications of D-SIFTS.

The blood-brain barrier (BBB) is a crucial part of brain anatomy as it is a specialized, protective barrier that ensures proper nutrient transport to the brain, ultimately leading to regulating proper brain function. However, it presents a major challenge in delivering pharmaceuticals to treat central nervous system (CNS) diseases due to this selectivity. A variety of different vehicles have been designed to deliver drugs across this barrier to treat neurodegenerative diseases, greatly impacting the patient’s quality of life. The two main types of vehicles used to cross the BBB are polymers and liposomes, which both encapsulate pharmaceuticals to allow them to transcytose the cells of the BBB. For Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and glioblastoma brain cancer, there are a variety of different nanoparticle treatments in development that increase the bioavailability and targeting ability of existing drugs or new drug targets to decrease symptoms of these diseases. Through these systems, nanomedicine offers a new way to target specific tissues, especially for the CNS, and treat diseases without the systemic toxicity that often comes with medications used currently.

Renal tubular epithelial cells (TECs) can initiate an adaptive or maladaptive response after injuries of different severity. Here, the authors elucidate a chromatin-mediated mechanism underlying the responses of TECs to varying kidney injuries.

BackgroundPulmonary infection caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) is a common and serious complication after brain injury. There are no definitive methods for its prediction and it is usually accompanied by a poor prognosis. This study aimed to construct and evaluate a nomogram based on patient data from the neurosurgical intensive care unit (NSICU) to predict the probability of MDR-AB pulmonary infection.MethodsIn this study, we retrospectively collected patient clinical profiles, early laboratory test results, and doctors’ prescriptions (66 variables). Univariate and backward stepwise regression analyses were used to screen the variables to identify predictors, and a nomogram was built in the primary cohort based on the results of a logistic regression model. Discriminatory validity, calibration validity, and clinical utility were evaluated using validation cohort 1 based on receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). For external validation based on predictors, we prospectively collected information from patients as validation cohort 2.ResultsAmong 2115 patients admitted to the NSICU between December 1, 2019, and December 31, 2021, 217 were eligible for the study, including 102 patients with MDR-AB infections (102 cases) and 115 patients with other bacterial infections (115 cases). We randomly categorized the patients into the primary cohort (70%, N=152) and validation cohort 1 (30%, N=65). Validation cohort 2 consisted of 24 patients admitted to the NSICU between January 1, 2022, and March 31, 2022, whose clinical information was prospectively collected according to predictors. The nomogram, consisting of only six predictors (age, NSICU stay, Glasgow Coma Scale, meropenem, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio), had significantly high sensitivity and specificity (primary cohort AUC=0.913, validation cohort 1 AUC=0.830, validation cohort 2 AUC=0.889) for early identification of infection and had great calibration (validation cohort 1,2 P=0.3801, 0.6274). DCA confirmed that the nomogram is clinically useful.ConclusionOur nomogram could help clinicians make early predictions regarding the onset of pulmonary infection caused by MDR-AB and implement targeted interventions.

Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) (B. dorsalis) is an important agricultural, major invasive, and quarantine pest that can cause significant damage to the economic value of the fruit and vegetable industry. Male bait is one of the most effective methods of surveying, monitoring, and controlling B. dorsalis. In our study, we constructed cDNA libraries using total RNA extracted independently from the antennae, mouthparts, and thoracic legs of male and female adults and the ovipositors of female adults and screened out four aldehyde-oxidase-related genes (AOX-related), C58800, C66700, C67485, and C67698. Molecular docking predictions showed that eight compounds, including 3,4-dimethoxycinnamyl alcohol, 3,4-dimethoxy-cinnamaldehyde, deet, ethyl N-acetyl-N-butyl-β-alaninate, n-butyl butyrate, n-butyl butyrate, ethyl butyrate, methyl eugenol, and ethyl acetate, could combine with proteins encoded by the four B. dorsalis AOX-related genes. Furthermore, QPCR was performed to confirm that four compounds, including 3,4-dimethoxy cinnamic aldehyde, butyl levulinic acid ethyl ester (mosquito repellent), butyl butyrate, and methyl eugenol, induced significant changes in the AOX-related genes of B. dorsalis. These results provide useful information and guidance for the batch screening of potentially useful compounds and the search for effective attractants of B. dorsalis.

To improve the low responsivity of the silicon avalanche photodiode in the near-ultraviolet wavelength range, we designed a near-ultraviolet highly responsive Si-APD basic structure with a multiplication layer neighboring the photosensitive surface through the analysis of the optical absorption characteristics, junction breakdown characteristics, and avalanche multiplication characteristics. The dark current and electric field distribution of the device were investigated. Meanwhile, the structural parameters of the surface non-depleted layer, multiplication layer, and absorption layer were optimized. It was found that the breakdown voltage of the device is 21.07 V. At an applied bias voltage of 20.02 V, the device exhibits a responsivity of 6.79–14.51 A/W in the wavelength range of 300–400 nm. These results provide valuable insights for the design of silicon avalanche photodiode with high responsivity in the near-ultraviolet range.

Abstract Objective Cancer-induced bone pain (CIBP) is a kind of pain with complex pathophysiology. Proteinase-activated receptor 2 (PAR-2) is involved in CIBP. This study explored the effects of PAR-2 on CIBP rats. Methods CIBP rat model was established by injecting Walker 256 rat breast cancer cells into the left tibia of female Sprague-Dawley rats and verified by tibial morphology observation, HE staining, and mechanical hyperalgesia assay. CIBP rats were injected with PAR-2 inhibitor, ERK activator, and CREB inhibitor through the spinal cord sheath on the 13th day after operation. CIBP behaviors were measured by mechanical hyperalgesia assay. On the 14th day after operation, L4-5 spinal cord tissues were obtained. PAR-2 expression, co-expression of PAR-2 and astrocyte marker GFAP, GFAP mRNA and protein levels and the ERK pathway-related protein levels were detected by Western blot, immunofluorescence double staining, RT-qPCR, and Western blot. Results CIBP rats had obvious mechanical hyperalgesia and thermal hyperalgesia from the 7th day after modeling; mechanical hyperalgesia threshold and thermal threshold were decreased; PAR-2 was increased in spinal cord tissues and was co-expressed with GFAP. PAR-2 silencing alleviated rat CIBP by inhibiting astrocyte activation. p-ERK/t-ERK and p-CREB/t-CREB levels in CIBP spinal cord were elevated, the ERK/CREB pathway was activated, while the ERK/CREB pathway was inhibited by PAR-2 silencing. The alleviating effect of PAR-2 inhibitor on hyperalgesia behaviors in CIBP rats were weakened by ERK activator, while were partially restored by CREB inhibitor. Conclusions PAR-2 knockdown inhibited the ERK/CREB pathway activation and astrocyte activation, thus alleviating CIBP in rats.

Summary: Diagnosis of primary brain tumors relies heavily on histopathology. Although various computational pathology methods have been developed for automated diagnosis of primary brain tumors, they usually require neuropathologists’ annotation of region of interests or selection of image patches on whole-slide images (WSI). We developed an end-to-end Vision Transformer (ViT) – based deep learning architecture for brain tumor WSI analysis, yielding a highly interpretable deep-learning model, ViT-WSI. Based on the principle of weakly supervised machine learning, ViT-WSI accomplishes the task of major primary brain tumor type and subtype classification. Using a systematic gradient-based attribution analysis procedure, ViT-WSI can discover diagnostic histopathological features for primary brain tumors. Furthermore, we demonstrated that ViT-WSI has high predictive power of inferring the status of three diagnostic glioma molecular markers, IDH1 mutation, p53 mutation, and MGMT methylation, directly from H&E-stained histopathological images, with patient level AUC scores of 0.960, 0.874, and 0.845, respectively.

Quantum entanglement in macroscopic systems plays an important role in quantum information processing. Here, we show that the steady-state entanglement between the two cavity modes in the macroscopic Laguerre–Gaussian (L–G) cavity optorotating system can be enhanced by placing a degenerate optical parametric amplifier (OPA) inside the cavity. The two L–G cavity modes are coupled to the same rotating mirror and are respectively driven at the red and blue mechanical sidebands. We use the logarithmic negativity to quantify the steady-state entanglement between the two cavity modes. We study the influences of the nonlinear gain and phase of the OPA, the temperature of the environment, and the angular momentums of the two cavity modes on the entanglement between the two cavity modes. In the cryogenic environment temperatures, when the angular momentums of the two cavity modes are identical, the enhancement of the entanglement between the two cavity modes by the OPA is the most significant.

Ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, have had a profound impact on millions of patients. In the past couple of decades, these diseases have been treated using conventional techniques but have also presented certain challenges and limitations that affect patient experience and outcomes. To address this, biomaterials have been used for ocular drug delivery, and a wide range of systems have been developed. This review will discuss some of the major classes and examples of biomaterials used for the treatment of prominent ocular diseases, including ocular implants (biodegradable and non-biodegradable), nanocarriers (hydrogels, liposomes, nanomicelles, DNA-inspired nanoparticles, and dendrimers), microneedles, and drug-loaded contact lenses. We will also discuss the advantages of these biomaterials over conventional approaches with support from the results of clinical trials that demonstrate their efficacy.

Depression, a complex epidemiological mental disorder, affects around 350 million people worldwide. Despite the availability of antidepressants based on monoamine hypothesis of depression, most patients suffer side effects from these drugs, including psychomotor impairment and dependence liability. Traditional Chinese medicine (TCM) is receiving more and more attention due to the advantages of high therapeutic performance and few side effects in depression treatment. However, complex multicomponents and multi-targets in TCM hinder our ability to identify the functional components and molecular mechanisms of its efficacy. In this study, we designed a novel strategy to capture the functional components and mechanisms of TCM based on a mathematical algorithm. To establish proof of principle, the TCM formula Danggui-Shaoyao-San (DSS), which possesses remarkable antidepressant effect but its functional components and mechanisms are unclear, is used as an example. According to the network motif detection algorithm, key core function motifs (CIM) of DSS in treating depression were captured, followed by a functional analysis and verification. The results demonstrated that 198 pathways were enriched by the target genes of the CIM, and 179 coincided with the enriched pathways of pathogenic genes, accounting for 90.40% of the gene enrichment pathway of the C-T network. Then the functional components group (FCG) comprising 40 components was traced from CIM based on the target coverage accumulation algorithm, after which the pathways enriched by the target genes of FCG were selected to elucidate the potential mechanisms of DSS in treating depression. Finally, the pivotal components in FCG of DSS and the related pathways were selected for experimental validation in vitro and in vivo. Our results indicated good accuracy of the proposed mathematical algorithm in sifting the FCG from the TCM formula, which provided a methodological reference for discovering functional components and interpreting molecular mechanisms of the TCM formula in treating complex diseases.

Hepatocellular carcinoma (HCC) is a complex issue in cancer treatment in the world at present. Matrine is the main active ingredient isolated from Sophora flavescens air and possesses excellent antitumor effects in HCC. However, the specific underlying mechanisms, especially the possible relationships between the anti-HCC effect of matrine and the related metabolic network of HCC, are not yet clear and need further clarification. In this study, an integrative metabolomic-based bioinformatics algorithm was designed to explore the underlying mechanism of matrine on HCC by regulating the metabolic network. Cell clone formation, invasion, and adhesion assay were utilized in HCC cells to evaluate the anti-HCC effect of matrine. A cell metabolomics approach based on LC-MS was used to obtain the differential metabolites and metabolic pathways regulated by matrine. The maximum activity contribution score model was developed and applied to calculate high contribution target genes of matrine, which could regulate a metabolic network based on the coexpression matrix of matrine-regulated metabolic genes and targets. Matrine significantly repressed the clone formation and invasion, enhanced cell–cell adhesion, and hampered cell matrix adhesion in SMMC-7721 cells. Metabolomics results suggested that matrine markedly regulated the abnormal metabolic network of HCC by regulating the level of choline, creatine, valine, spermidine, 4-oxoproline, D-(+)-maltose, L-(−)-methionine, L-phenylalanine, L-pyroglutamic acid, and pyridoxine, which are involved in D-glutamine and D-glutamate metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, etc. Our proposed metabolomic-based bioinformatics algorithm showed that the regulating metabolic networks of matrine exhibit anti-HCC effects through acting on MMP7, ABCC1, PTGS1, etc. At last, MMP7 and its related target β-catenin were validated. Together, the metabolomic-based bioinformatics algorithm reveals the effects of the regulating metabolic networks of matrine in treating HCC relying on the unique characteristics of the multitargets and multipathways of traditional Chinese medicine.

Subdural hematoma (SDH) is one of the most lethal types of traumatic brain injury. SDH caused by Intracranial Pressure Reduction (ICPR) is rare, and the mechanism remains unclear. Here, we report three cases of SDH that occurred after substandard cupping therapy and are conjected to be associated with ICPR. All of them had undergone cupping treatments. On the last cupping procedure, they experienced a severe headache after the cup placed on the occipital-neck junction (ONJ) was suddenly removed and were diagnosed with SDH the next day. In standard cupping therapy, the cups are not usually placed on the ONJ. We speculate that removing these cups on the soft tissue over the cisterna magna repeatedly created localized negative pressure, caused temporary but repeated ICPR, and eventually led to SDH development. The Monro-Kellie Doctrine can explain the mechanism behind this - it states that the intracranial pressure is regulated by a fixed system, with any change in one component causing a compensatory change in the other. The repeated ICPR promoted brain displacement, tearing of the bridging veins, and development of SDH. The literature was reviewed to illustrate the common etiologies and therapies of secondary ICPR-associated SDH. Despite the popularity of cupping therapy, its side effects are rarely mentioned. This case is reported to remind professional technicians to fully assess a patient's condition before cupping therapy and ensure that the cups are not placed at the ONJ.

Infrared imaging spectrometers detect and identify targets by collecting spectral and image information. However, when detecting small temperature differences and dynamic targets, the accuracy of infrared detection is reduced, the traditional scanning structure detection time is longer, the real-time performance is poor and it is easy to introduce motion artifacts. This paper proposes an infrared polarization snapshot spectral imaging system (PSIFTIS) based on a polarizer array, a lens array and a roof-shaped stepped micromirror. Polarized light can solve the problem of small-temperature-difference target recognition by characterizing the surface properties of materials. Lens arrays utilize multi-aperture imaging to achieve snapshot detection of targets. The system can obtain 4D data information, including polarization, in a single measurement cycle. This study completed the overall optical design of a PSIFTIS and an optical simulation experiment using it. Finally, a system prototype was built in the laboratory and a polarization spectrum detection experiment was carried out. The experimental results show that the PSIFTIS could accurately obtain the polarization spectrum information for the target, the spectral resolution reached 7.8 cm−1 and the Stokes measurement error was less than 5%.

The blood-brain barrier (BBB) is the most specialized biological barrier in the body. This configuration of specialized cells protects the brain from invasion of molecules and particles through formation of tight junctions. To learn more about transport to the brain, in vitro modeling of the BBB is continuously advanced. The types of models and cells selected vary with the goal of each individual study, but the same validation methods, quantification of tight junctions, and permeability assays are often used. With Transwells and microfluidic devices, more information regarding formation of the BBB has been observed. Disease models have been developed to examine the effects on BBB integrity. The goal of modeling is not only to understand normal BBB physiology, but also to create treatments for diseases. This review will highlight several recent studies to show the diversity in model selection and the many applications of BBB models in in vitro research.

ObjectiveTo investigate the clinicopathological characteristics, molecular genetic characteristics and prognosis of extraventricular neurocytoma located in the sellar/suprasellar region.MethodsSeven archived tumor samples derived from 4 patients with neurocytoma in the sellar/suprasellar region were collected from the First Affiliated Hospital of Fujian Medical University and the Affiliated Hospital of Qingdao University and retrospectively analyzed for clinical manifestations, imaging features, and histopathological features. Neuronal and pituitary biomarkers and molecular features were detected in these tumor tissues by immunohistochemistry and FISH or Sanger sequencing. The related literature was reviewed.ResultsThree patients were female, while 1 was male, with an average age of 35.5 years (range: 27 to 45 years). The initial manifestations were mainly headache and blurred vision in both eyes. The first MRI examination showed marginally enhancing masses in the intrasellar or intra- to suprasellar region. The diagnosis of pituitary adenomas was based on imaging features. The levels of pituitary hormones were normal. Histologically, the tumor cells were arranged in a sheet-like, monotonous architecture and were uniform in size and shape with round to oval, exquisite and hyperchromatic nuclei, which densely packed close to one another and were separated only by a delicate neuropil background. There was no evident mitosis, necrosis or microvascular proliferation. The three cases of recurrent tumors were highly cellular and showed increased mitotic activity. Immunohistochemically, the tumor cells were positive for syn, CR, CgA, and vasopressin and were focally positive for NeuN, TTF-1, NF, CK8, vimentin, and S100 proteins. Other markers, including IDH1, BRAF VE1, Olig-2, and EMA, were negative. Pituitary transcription factors and anterior pituitary hormones were negative. Molecular genetic testing showed that the tumor cells lacked IDH gene mutations, LOH of 1p/19q, MYCN amplification, and EGFR alteration. With a median follow-up of 74.5 months (range 23 to 137 months), 3 patients relapsed at 11, 50, and 118 months after the initial surgery.ConclusionThe morphological features and immunophenotypes of neurocytoma in the sellar/suprasellar region are similar to those of classic central neurocytoma. The prognosis is relatively good. Gross-subtotal resection and atypical subtype may be related to tumor recurrence.

Abstract Formation of biomolecular condensates by phase separation has recently emerged as a new principle for regulating gene expression in response to extracellular signaling. However, the molecular mechanisms underlying the coupling of signal transduction and gene activation through condensate formation, and how dysregulation of these mechanisms contributes to disease progression, remain elusive. Here, the authors report that CREB‐regulated transcription coactivator 2 (CRTC2) translocates to the nucleus and forms phase‐separated condensates upon activation of cAMP signaling. They show that intranuclear CRTC2 interacts with positive transcription elongation factor b (P‐TEFb) and activates P‐TEFb by disrupting the inhibitory 7SK snRNP complex. Aberrantly elevated cAMP signaling plays central roles in the development of autosomal dominant polycystic kidney disease (ADPKD). They find that CRTC2 localizes to the nucleus and forms condensates in cystic epithelial cells of both mouse and human ADPKD kidneys. Genetic depletion of CRTC2 suppresses cyst growth in an orthologous ADPKD mouse model. Using integrative transcriptomic and cistromic analyses, they identify CRTC2‐regulated cystogenesis‐associated genes, whose activation depends on CRTC2 condensate‐facilitated P‐TEFb recruitment and the release of paused RNA polymerase II. Together, their findings elucidate a mechanism by which CRTC2 nuclear condensation conveys cAMP signaling to transcription elongation activation and thereby promotes cystogenesis in ADPKD.

Evolution of accretion disk and corona during outbursts in black hole binary systems is still unclear. Here, the authors show spectral analysis of MAXI J1820+070 and propose a scenario of a dynamical corona to explain the evolution of the reflection fraction observed by Insight-HXMT.

In recent years, various fields have established an urgent need for real-time online measurement of infrared spectra. To this end, reducing the weight and size of infrared spectrometers is particularly important. This paper reports a micro-optical element static Fourier transform spectrometer (MOESFTS) with a working wavelength from $3.7~\mu \text{m}$ to $4.8~\mu \text{m}$ . This spectrometer is entirely composed of micro-optical elements, and its interference system comprises stepped micromirrors and a lightweight beam splitter to realize a lightweight, miniaturized instrument capable of static real-time spectrum measurements. The micro-optical element microlens array leads to the acquisition of interferogram in the form of two-dimensional point-array in the MOESFTS. Therefore we establish a field-of-view integral model of the interference-image point intensity to analyze the influence of the field of view on the reconstructed spectrum. We complete the optical design of the micro-optical collimator (MOC) lens and the micro-optical relay (MOR) lens. And an effective processing algorithm for spectral reconstruction from two-dimensional point-array is presented. A prototype was designed and constructed, and spectral calibration was completed. The spectra of acetonitrile (CH3CN) and carbon dioxide (CO2) were measured, the experimental results show that the spectral peak drift errors were found to be less than 0.18%.

Endoscopic inspection is an important non-destructive testing method. Traditional 3D endoscopic reconstruction methods, such as polarization reconstruction and shading reconstruction, have the drawbacks of not determining the object’s actual size and positional information. The stereo vision method is limited by its operating principles and has the issue of sparse reconstructed point clouds. These drawbacks greatly restrict the applications of the endoscope. Therefore, this work proposes a joint dense 3D reconstruction method for endoscopic images of weak texture scenes. This method uses the shading reconstruction normal to correct the polarization reconstruction normal, then uses coordinate conversion and point cloud fusion to convert the polarization and shading 3D reconstruction results from the pixel coordinate system to the world coordinate system. Finally combines the reconstruction results from the world coordinate system’s polarization, shading, and stereo vision. The fusion coefficients are obtained by solving the minimum error model, and then a complete and detailed 3D reconstruction surface was obtained in the world coordinate system. This method could avoid the difficulty of obtaining real coordinates for the 3D reconstruction of polarization and shading and prevent the issue of the sparse point cloud afforded by stereo vision reconstruction for weak texture scenes. The combined dense 3D reconstruction method had an average error of < 1% for length measurement of a 3D curve, which is highly significance for industrial endoscopic inspection.

Fungi represent an important source of bioactive secondary metabolites (SMs), which have wide applications in many fields, including medicine, agriculture, human health, and many other industries. The genes involved in SM biosynthesis are usually clustered adjacent to each other into a region known as a biosynthetic gene cluster (BGC). The recent advent of a diversity of genetic and genomic technologies has facilitated the identification of many cryptic or uncharacterized BGCs and their associated SMs. However, there are still many challenges that hamper the broader exploration of industrially important secondary metabolites. The recent advanced CRISPR/Cas system has revolutionized fungal genetic engineering and enabled the discovery of novel bioactive compounds. In this review, we firstly introduce fungal BGCs and their relationships with associated SMs, followed by a brief summary of the conventional strategies for fungal genetic engineering. Next, we introduce a range of state-of-the-art CRISPR/Cas-based tools that have been developed and review recent applications of these methods in fungi for research on the biosynthesis of SMs. Finally, the challenges and limitations of these CRISPR/Cas-based systems are discussed and directions for future research are proposed in order to expand their applications and improve efficiency for fungal genetic engineering.

The stepped micro-mirror imaging Fourier transform spectrometer (SIFTS) has the advantages of high throughput, compactness, and stability. However, the systematic errors in the interference core of the SIFTS have a significant impact on the interferogram and the reconstructed spectrum. In order to reduce the influence of systematic errors, a transfer error model of the systematic errors in the interference core of the SIFTS is established, and an interferogram and spectrum calibration method is presented, which combines the least squares fitting calibration and the row-by-row fast Fourier transform-inverse fast Fourier transform (FFT-IFFT) flat-field calibration. The experimental results show that the methods can sufficiently reduce the influence of systematic errors in the interference core of the SIFTS, such as the interferogram fringe tilt, the peak position shift of the reconstructed spectrum, and the error of spectral response.

A variety of engineered nanoparticles, including lipid nanoparticles, polymer nanoparticles, gold nanoparticles, and biomimetic nanoparticles, have been studied as delivery vehicles for biomedical applications. When assessing the efficacy of a nanoparticle-based delivery system, in vitro testing with a model delivery system is crucial because it allows for real-time, in situ quantitative transport analysis, which is often difficult with in vivo animal models. The advent of tissue engineering has offered methods to create experimental models that can closely mimic the 3D microenvironment in the human body.This review paper overviews the types of nanoparticle vehicles, their application areas, and the design strategies to improve delivery efficiency, followed by the uses of engineered microtissues and methods of analysis. In particular, this review highlights studies on multicellular spheroids and other 3D tissue engineering approaches for cancer drug development. The use of bio-engineered tissues can potentially provide low-cost, high-throughput, and quantitative experimental platforms for the development of nanoparticle-based delivery systems.

Summary: Bio-inspired surfaces enabling wet adhesion management are of significant interest for applications in the field of biomedicine, as components of bionic robots and as wearable devices. In the course of biological evolution, many organisms have evolved wet adhesive surfaces with strong attachment ability. Insects enhance their adhesion on contact substrates using secreted adhesive liquids. Here we discuss concepts of bio-inspired wet adhesion. First, remaining challenges associated with the understanding and the design of biological and artificial wet adhesive systems as well as strategies to supply adhesive liquids to their contact surfaces are reviewed. Then, future directions to construct wet adhesive surfaces with liquids are discussed in detail. Finally, a model of wet adhesion management with liquids is suggested, which might help the design of next-generation bio-inspired wet adhesive surfaces.

ObjectiveTo investigate the clinicopathologic features of pituitary adenoma with neuronal differentiation.MethodsFour patients with mixed gangliocytoma-pituitary adenomas between January 2011 and January 2021 and 111 new-onset patients with adenomas between January 2019 and June 2021 who attended the First Affiliated Hospital of Fujian Medical University were included in the study. The histological and immunohistochemical findings were analyzed. Neuronal differentiation marker staining was performed on new-onset adenomas, and the related literature was reviewed.ResultsAltogether, more than 100 mixed gangliocytoma-pituitary adenoma cases have been reported in the literature until now, of which pituitary-specific POU-class homeodomain transcription 1 (PIT1) positive adenomas are more frequently observed. In the present study, all 4 patients we described were female, aged 29 to 53 years (mean 39 years). Clinically, 3/4 patients presented with acromegaly, and 1/2 patients presented with headache. Histologically, the tumor was composed of two distinct mixed components. The one was a population of neoplastic ganglionic cells with large nuclei, prominent nucleoli, and abundant basophilic cytoplasm embedded in a fibrillary background. Stains of chromograninA (CgA), synaptophysin (Syn), Calretinin (CR) were positive. Axotomy-like expression was observed in neurofilament (NF) staining. PIT1 was expressed in partial ganglionic cells in all cases. The other component was a population of small uniform cells with round nuclei and acidophilic cytoplasm. Prolactin (PRL) and growth hormone (GH) were positive in all 4 cases. PIT1 was positive in the nuclei of adenomas. Although adenomas and ganglionic regions varied in histology, there was a population of cells with neuronal differentiation expressing PIT1. Additionally, axotomy-like expression of NF staining could be seen in a distant area of adenoma regions. A total of 111 cases of adenomas without ganglionic cells were included in this study, including 7 cases with neuronal differentiation. Among them, 4 cases were prolactinomas, 2 cases were somatotroph adenomas, and 1 case was corticotroph adenoma. 6/7 cases were PIT1-positive adenomas. And the remaining one case is T-PIT-positive adenoma.ConclusionsMixed gangliocytoma-pituitary adenomas are rare tumors with neuronal differentiation. The majority of MGAs are associated with endocrinopathies, mainly acromegaly. Our results suggest that PIT1-positive pituitary adenomas may have neural differentiation potential, which may not be unusual. This indication supports the possibility that the neuronal transdifferentiation of adenomatous cells is a possible mechanism, and the underlying mechanism requires further elucidation.

Abstract Vigorous development of electric vehicles is one way to achieve global carbon reduction goals. However, fires caused by thermal runaway of the power battery has seriously hindered large‐scale development. Adding thermal runaway retardants (TRRs) to electrolytes is an effective way to improve battery safety, but it often reduces electrochemical performance. Therefore, it is difficult to apply in practice. TRR encapsulation is inspired by the core–shell structures such as cells, seeds, eggs, and fruits in nature. In these natural products, the shell isolates the core from the outside, and has to break as needed to expose the core, such as in seed germination, chicken hatching, etc. Similarly, TRR encapsulation avoids direct contact between the TRR and the electrolyte, so it does not affect the electrochemical performance of the battery during normal operation. When lithium‐ion battery (LIB) thermal runaway occurs, the capsules release TRRs to slow down and even prevent further thermal runaway. This review aims to summarize the fundamentals of bioinspired TRR capsules and highlight recent key progress in LIBs with TRR capsules to improve LIB safety. It is anticipated that this review will inspire further improvement in battery safety, especially for emerging LIBs with high‐electrochemical performance.

Abstract Objective This study aimed to investigate the differences in the relationship between hair cortisol concentration (HCC) and psychosocial stress, social support, clinical features, clinical course, and outcome in schizophrenia and bipolar disorder. Methods A total of 109 schizophrenia patients, 93 bipolar disorder patients and 86 healthy controls between 18 and 60 years old were enrolled in the study. Linear regression and factor analysis were employed to examine and compare the relationship between HCC and childhood trauma, the number of stressful life events, the amount of social support in the three months before the hair cortisol assessment, clinical fearures, clinical course, and outcome in schizophrenia and bipolar disorder. Results HCC is significantly associated with clinical syndromes, including depression–anxiety factor of Positive and Negative Syndrome Scale in schizophrenia patients, and thought disorder in bipolar disorder patients. However, HCC is positively related to social support and personality traits only in schizophrenia patients but not in bipolar disorder patients. Factor analysis indicates schizophrenia and bipolar disorder share a very similar but somewhat different structure in terms of HCC, psychosocial stress, social support, clinical features, clinical course, and outcome. Conclusion Findings support that schizophrenia and bipolar disoder have a significant overlap in both clinical characteristics and enviromental risk factors. Aberrant HCC contributes to the complexity of clinical characteristics mainly in schizophrenia.

Traditional Chinese medicine (TCM) usually plays therapeutic roles on complex diseases in the form of formulas. However, the multicomponent and multitarget characteristics of formulas bring great challenges to the mechanism analysis and secondary development of TCM in treating complex diseases. Modern bioinformatics provides a new opportunity for the optimization of TCM formulas. In this report, a new bioinformatics analysis of a computational network pharmacology model was designed, which takes Chai-Hu-Shu-Gan-San (CHSGS) treatment of depression as the case. In this model, effective intervention space was constructed to depict the core network of the intervention effect transferred from component targets to pathogenic genes based on a novel node importance calculation method. The intervention-response proteins were selected from the effective intervention space, and the core group of functional components (CGFC) was selected based on these intervention-response proteins. Results show that the enriched pathways and GO terms of intervention-response proteins in effective intervention space could cover 95.3 and 95.7% of the common pathways and GO terms that respond to the major functional therapeutic effects. Additionally, 71 components from 1,012 components were predicted as CGFC, the targets of CGFC enriched in 174 pathways which cover the 86.19% enriched pathways of pathogenic genes. Based on the CGFC, two major mechanism chains were inferred and validated. Finally, the core components in CGFC were evaluated by in vitro experiments. These results indicate that the proposed model with good accuracy in screening the CGFC and inferring potential mechanisms in the formula of TCM, which provides reference for the optimization and mechanism analysis of the formula in TCM.