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Polylactic acid (PLA) composites reinforced with rice husk and glass fiber can improve the properties in the aera of the material for vehicle application. In this work, the PLA composite was made and its properties were evaluated using scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). SEM observed that the polymer matrix contained a uniform dispersion of 10 wt% rice husks. The tensile strength and bending strength of the composite are 45.8 and 48.2 MPa, respectively, which are 52% and 41% higher than that of the base material PLA. TGA revealed that the thermal stability of the composite deteriorated with increasing rice husk content. The DTG curve indicated that the incorporation of rice husk and glass fiber led to a reduction in the maximum degradation rate of the PLA matrix. As a result, the thermal degradation of the PLA composite exhibited enhanced stability. The average apparent activation energy (Ea) of the composite, determined using the Friedman (FD), Flynn Wall Ozawa (FWO), Starink (ST), and Kissinger (KS) models, falls within the range of 90 to 120 kJ mol−1. Highlights: Silane coupling agent was used to improve the interfacial compatibility of fillers.The synergistic action of rice husk and glass fiber fillers enhances the mechanical properties of polylactic acid composites.The mean apparent activation energy (Ea) of the composite was calculated using four models, with values in the range of 90 to 120 kJ mol−1.The Flynn Wall Ozawa and Starink models showed better stability against temperature changes compared to the Friedman model. [ABSTRACT FROM AUTHOR]

Background: Triple‐negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Previous studies have found that fibroblast growth factor receptor 4 (FGFR4) plays a crucial role in tumor development and metastasis. However, the potential role and underlying mechanisms of FGFR4 in the progression of TNBC remain unclear. Methods: Statistical analysis of FGFR4 expression data in public databases was used to reveal its role in TNBC. qRT‐PCR was used to detect FGFR4 expression levels. The impact of FGFR4 level changes on TNBC cell proliferation was assessed using CCK‐8 and colony formation assays, while Transwell invasion assays and JC‐1 staining were employed to analyze the effects of FGFR4 level changes on the invasiveness and survival capability of TNBC cells. Differentially expressed genes were subjected to Gene Ontology, KEGG, and GSEA enrichment analyses to identify associated signaling pathways. Additionally, Oil Red O staining, fatty acid metabolite detection, and Western blot analysis were used to investigate the impact of FGFR4 and its inhibitor fisogatinib, as well as the AKT activator SC79, on the metabolic reprogramming of fatty acids in TNBC cells. Results: FGFR4 was found to be upregulated in breast cancer and correlated with poorer patient outcomes. Inhibition of FGFR4 resulted in reduced cell growth and invasion in TNBC cells. It also led to increased lipid accumulation, upregulated lipid biosynthesis‐related genes, and downregulated lipolysis‐related genes. Mechanistically, FGFR4 inhibition suppressed the activation of the AKT/RYR2 signaling pathway. Reactivating the AKT pathway reversed the suppressive effects of FGFR4 inhibition on TNBC progression. Conclusion: Dysregulated FGFR4 activates the AKT/RYR2 axis, leading to tumor proliferation, invasion, and altered lipid metabolism in TNBC. FGFR4 inhibition could potentially serve as a novel therapeutic strategy for TNBC treatment. [ABSTRACT FROM AUTHOR]

The clinical outcomes of osteosarcoma are relatively dismal. As immunotherapy has revolutionized treatment for solid tumors, exploring novel immunotherapy‐related therapeutic targets for osteosarcoma is important. In this study, we aimed to establish the connection between RNA modification and immunotherapy in osteosarcoma to identify novel therapeutic targets. An RNA modification‐related signature was first developed using weight gene correlation network analysis and a machine‐learning algorithm, random forest. The signature's prognostic value, drug prediction, and immune characteristics were analyzed. EIF4G2 from the signature was next identified as a critical immunotherapy determinant. EIF4G2 could also promote tumor proliferation, migration, and M2 macrophage migration by single‐cell sequencing analysis and in vitro validation. Our signature and EIF4G2 are expected to provide valuable insights into the clinical management of osteosarcoma. [ABSTRACT FROM AUTHOR]

As an effective means to promote photoinduced carrier separation, the construction of Z‐scheme heterojunction photocatalysts can be widely used for the degradation of organic pollutants. In this work, an innovative peanut shell biochar/Ag3PO4/AgI ternary composite was prepared, and the chemical compositions, structural morphology, optical and photoelectrochemical properties of the photocatalyst were characterized. The peanut shell biochar/Ag3PO4/AgI composite delivered a high photodegradation efficiency of MB at 99.7 % in 60 min with kinetic constant of 0.0366 min−1, which is about 3.81, 9.89, and 1.17 times that Ag3PO4 (0.0096 min−1), AgI (0.0037 min−1) and Ag3PO4/AgI (0.0313 min−1), respectively. Meanwhile, the composite also exhibits excellent photocatalytic activity for methyl orange, rhodamine B, congo red, tetracycline and ofloxacin. Based on radical capture experiments and photoelectrochemical test, the possible photocatalytic mechanism was revealed. Compared with monomers, biochar/Ag3PO4/AgI exhibits higher photocatalytic degradation activity under visible light irradiation, which was due to the introduction of electron‐transporting biochar into the composite, and the formation of heterostructure between Ag3PO4 and AgI, which enhance the separation rate of photoinduced carriers. The excellent stability and photocatalytic activity make peanut shell biochar/Ag3PO4/AgI an ideal photocatalyst to solve environmental crisis. [ABSTRACT FROM AUTHOR]

Two‐dimensional (2D) non‐layered materials, along with their unique surface properties, offer intriguing prospects for sensing applications. Introducing mechanical degrees of freedom is expected to enrich the sensing performances of 2D non‐layered devices, such as high frequency, high tunability, and large dynamic range, which could lead to new types of high performance nanosensors. Here, we demonstrate 2D non‐layered nanomechanical resonant sensors based on β‐In2S3, where the devices exhibit robust nanomechanical vibrations up to the very high frequency (VHF) band. We show that such device can operate as pressure sensor with broad range (from 10−3 Torr to atmospheric pressure), high linearity (with a nonlinearity factor as low as 0.0071), and fast response (with an intrinsic response time less than 1 μs). We further unveil the frequency scaling law in these β‐In2S3 nanomechanical sensors and successfully extract both the Young's modulus and pretension for the crystal. Our work paves the way towards future wafer‐scale design and integrated sensors based on 2D non‐layered materials. [ABSTRACT FROM AUTHOR]

Sugar substitutes are popular due to their akin taste and low calories. However, excessive use of aspartame and erythritol can have varying effects. While D‐allulose is presently deemed a secure alternative to sugar, its excessive consumption is not devoid of cellular stress implications. In this study, the evolution of Escherichia coli Nissle 1917 (EcN) is directed to utilize allulose as sole carbon source through a combination of adaptive laboratory evolution (ALE) and fluorescence‐activated droplet sorting (FADS) techniques. Employing whole genome sequencing (WGS) and clustered regularly interspaced short palindromic repeats interference (CRISPRi) in conjunction with compensatory expression displayed those genetic mutations in sugar and amino acid metabolic pathways, including glnP, glpF, gmpA, nagE, pgmB, ybaN, etc., increased allulose assimilation. Enzyme‐substrate dynamics simulations and deep learning predict enhanced substrate specificity and catalytic efficiency in nagE A247E and pgmB G12R mutants. The findings evince that these mutations hold considerable promise in enhancing allulose uptake and facilitating its conversion into glycolysis, thus signifying the emergence of a novel metabolic pathway for allulose utilization. These revelations bear immense potential for the sustainable utilization of D‐allulose in promoting health and well‐being. [ABSTRACT FROM AUTHOR]

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) characterized by 30 mutations in its spike protein, has rapidly spread worldwide since November 2021, significantly exacerbating the ongoing COVID‐19 pandemic. In order to investigate the relationship between these mutations and the variant's high transmissibility, we conducted a systematic analysis of the mutational effect on spike–angiotensin‐converting enzyme‐2 (ACE2) interactions and explored the structural/energy correlation of key mutations, utilizing a reliable coarse‐grained model. Our study extended beyond the receptor‐binding domain (RBD) of spike trimer through comprehensive modeling of the full‐length spike trimer rather than just the RBD. Our free‐energy calculation revealed that the enhanced binding affinity between the spike protein and the ACE2 receptor is correlated with the increased structural stability of the isolated spike protein, thus explaining the omicron variant's heightened transmissibility. The conclusion was supported by our experimental analyses involving the expression and purification of the full‐length spike trimer. Furthermore, the energy decomposition analysis established those electrostatic interactions make major contributions to this effect. We categorized the mutations into four groups and established an analytical framework that can be employed in studying future mutations. Additionally, our calculations rationalized the reduced affinity of the omicron variant towards most available therapeutic neutralizing antibodies, when compared with the wild type. By providing concrete experimental data and offering a solid explanation, this study contributes to a better understanding of the relationship between theories and observations and lays the foundation for future investigations. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Chiral supramolecular assembly of π‐conjugated luminophores provides a promising avenue for enhancing circularly polarized luminescence. In this study, we shed light on the impact of π‐conjugation length on circularly polarized luminescent performance of the resulting supramolecular assemblies, by designing a tetra‐cyanostilbene monomeric compound alongside two dicyanostilbene control compounds. These cyanostilbene‐based compounds possess the ability to form chiral supramolecular polymers in toluene, driven by a synergistic combination of intermolecular hydrogen bonding and π–π stacking interactions. The extended π‐aromatic skeleton brings bathochromic‐shifted fluorescence and enhanced intermolecular stacking capability for the tetra‐cyanostilbene compound. Consequently, chiral supramolecular assemblies formed by the tetra‐cyanostilbene compound demonstrate a remarkable two‐fold increase in glum values relative to the assemblies formed by the dicyanostilbene compounds. Overall, this study provides valuable insights into the relationship between π‐conjugation length and the circularly polarized luminescent performance of π‐conjugated supramolecular assemblies. [ABSTRACT FROM AUTHOR]

As a representative technique in electronics, the Smith Chart provides a fast, less‐computation, and graphical approach to solve the problems related to impedance matching. In this paper, we transplanted the Smith Chart into the design and analysis of a microwave metamaterial absorber (meta‐absorber) to develop an analytical and graphical approach for impedance matching of electromagnetic wave absorption. Before the structural design, four traces on the Smith Chart plane from the load to arrive at the impedance matching point (the center of the Smith Chart) can be graphically found to obtain perfect absorption. Then, we have designed four impedance matching circuit networks made of resistance, inductance, and capacitive elements and transmission lines to fit the four traces. Then, the matching circuits are mapped into the meta‐absorber structure by using three types of proposed layers. The full simulation method based on the finite element method is used to verify the proposed concept. Furthermore, an external dielectric loading strategy has been developed to achieve good angular stability up to 60° for the radar cross section reduction under transverse electric and transverse mangetic polarization incidence. The proposed method may provide a convenient way for various microwave devices, such as antennas. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is a very aggressive bone tumor mainly affecting teens and young adults. Disulfidptosis is a metabolic‐related form of regulated cell death. However, the interconnection between disulfidptosis and osteosarcoma has not been explored. Methods: In the present study, disulfidptosis‐related clusters were identified in osteosarcoma using the nonnegative matrix factorization clustering method. PABPC3 was identified as a hazardous gene in osteosarcoma using machine learning algorithms, CoxBoost, and Random Survival Forest. The prognostic value, pathway annotation, immune characteristics, and drug prediction of PABPC3 were systematically explored. MTT (i.e., 3‐(4, 5‐dimethyl thiazol‐2‐yl)‐2,5‐diphenytetrazolium bromide), EdU (ie. 5‐ethyny‐2'‐deoxvuridine), and Transwell assays were used for in vitro validation of PABPC3. Results: The disulfidptosis‐related clusters could distinguish survival outcomes of osteosarcoma patients. PABPC3 could predict survival outcomes, immune activity, and drug response in osteosarcoma patients. Besides, PABPC3 was proven to facilitate the proliferation and migration of osteosarcoma. Conclusions: The present study is expected to establish the bridge between disulfidptosis and osteosarcoma. PABPC3 is expected to be further explored as a therapeutic target in osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death (PCD) is a natural process in which cells undergo controlled self‐destruction, which plays a crucial role in maintaining tissue homeostasis and eliminating damaged or unnecessary cells. The connection between PCD and osteosarcoma was explored in the present study. Methods: Twelve types of PCD were collected for developing a prognostic signature in osteosarcoma using machine learning algorithms. The prognostic value, pathway annotation and drug prediction of the signature were explored. Results: Telomerase reverse transcriptase (TERT) was found to be a potent hazardous marker in osteosarcoma and could facilitate the proliferation and migration of osteosarcoma. Conclusions: In summary, the present study has developed a prognostic signature for osteosarcoma and identifies TERT as a potent hazardous gene. The study suggests that further research is needed to address the underlying mechanism of how TERT affects the immune response in osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: In recent decades, osteosarcoma has remained the most prevalent kind of malignant tumor. An important and crucial factor in immunotherapy is antigen processing and presentation (APP). The specific functions and pathogenic processes of APP in osteosarcoma have not, however, been studied. Methods: Patients with osteosarcoma were divided into groups using APP‐related genes. Machine learning was used to further build the APP‐related score. Investigated in‐depth were the prognostic relevance of the score, mutation features, immunological aspects, and pharmacological prediction performance. Investigations of the prognostic utility, immunological traits, drug prediction effectiveness and immunotherapy prediction of BNIP3 were performed in‐depth. Results: Investigations by cell counting kit‐8, Transwell and 5‐ethynyl‐2‐deoxyuridine (EdU) demonstrated that BNIP3 is an osteosarcoma tumor accelerator. The osteosarcoma gene BNIP3 may promote macrophage migration. The APP‐related score shows potential for clinical use. Conclusions: It was anticipated that more in vitro and in vivo studies would confirm BNIP3's tumorigenic and immunogenic processes in osteosarcoma. [ABSTRACT FROM AUTHOR]

This paper presents a viable coating design for the production of waterborne coatings using PUA, Silicone‐modified‐PUA, Al‐SiO2, and PTFE as key ingredients. The coatings are prepared through an air compression spraying technique followed by a photocuring procedure. The resulting PUA/Silicone‐modified‐PUA/Al‐SiO2/PTFE coating exhibits exceptional properties including high hardness, low surface tension, and a low coefficient of friction. Experimental findings reveal noteworthy characteristics of the coating. It possesses a gloss level of 4–6°, a hardness of 492.69 N/mm, an elasticity modulus of 11469.94 MPa, a surface roughness of 0.87 μm, a dynamic coefficient of friction of 0.125 μN, and a surface tension of 0.4967 mN/m. To assess its performance, the coating underwent rigorous tests such as the CS‐5 Wool Touchpad Shinning Friction test with a 200 g load over 250,000 cycles. It exhibited minimal changes in gloss (≤2°) and color difference (∆E ≤ 0.75). Additionally, the CS‐10 abrasive head Optical Surface Taber Abrasion Resistance test was conducted using a 500 g load for 10 cycles, resulting in a Class 1 rating, and after 100 cycles, it achieved a Class 3 rating. This demonstrates its remarkable resistance to tribological environments, enduring tapping, touching, and scraping by fingers over extended periods. [ABSTRACT FROM AUTHOR]

Bladder carcinoma (BC) recurrence is a major clinical challenge, and targeting the tumor microenvironment (TME) is a promising therapy. However, the relationship between individual TME components, particularly cancer‐associated fibroblasts (CAFs), and tumor recurrence is unclear. Here, TME heterogeneity in primary and recurrent BC is investigated using single‐cell RNA sequence profiling of 62 460 cells. Two cancer stem cell (CSC) subtypes are identified in recurrent BC. An inflammatory CAF subtype, ICAM1+ iCAFs, specifically associated with BC recurrence is also identified. iCAFs are found to secrete FGF2, which acts on the CD44 receptor of rCSC‐M, thereby maintaining tumor stemness and epithelial‐mesenchymal transition. Additionally, THBS1+ monocytes, a group of myeloid‐derived suppressor cells (MDSCs), are enriched in recurrent BC and interacted with CAFs. ICAM1+ iCAFs are found to secrete CCL2, which binds to CCR2 in MDSCs. Moreover, elevated STAT3, NFKB2, VEGFA, and CTGF levels in iCAFs reshape the TME in recurrent tumors. CCL2 inhibition in an in situ BC mouse model suppressed tumor growth, decreased MDSCs and Tregs, and fostered tumor immune suppression. The study results highlight the role of iCAFs in TME cell–cell crosstalk during recurrent BC. The identification of pivotal signaling factors driving BC relapse is promising for the development of novel therapies. [ABSTRACT FROM AUTHOR]

Objective: The present study assessed the diagnostic and prognostic significance of endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) for suspected intrathoracic metastasis after HNC treatment. Methods: A retrospective analysis was conducted on 75 patients with a prior history of head and neck cancer treatment who underwent EBUS‐TBNA for suspected intrathoracic metastases between March 2012 and December 2021. Results: A total of 126 targeted lesions, including 107 mediastinal/hilar lymph nodes and 19 intrapulmonary/mediastinal masses, were sampled. The metastatic head and neck cancer (HNC) cases detected by EBUS‐TBNA consisted of nasopharyngeal carcinoma (n = 24), oropharyngeal carcinoma (n = 3), hypopharynx carcinoma (n = 6), laryngeal carcinoma (n = 6), and oral cavity carcinoma (n = 6). Cases with negative EBUS‐TBNA results consisted of tuberculosis (n = 9), sarcoidosis (n = 3), anthracosis (n = 9), and reactive lymphadenitis (n = 9). Six false‐negative cases were found among the 75 patients with suspected intrathoracic metastases. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the EBUS‐TBNA procedure for metastatic HNC were 88.2, 100.0, 100.0, 80, and 92.0%, respectively. The diagnosis of HNC intrathoracic metastasis by EBUS‐TBNA correlated with an adverse prognosis in terms of overall survival (OS) (P =.008). The log‐rank univariate analysis and Cox regression multivariate analysis results indicated that the detection of metastatic HNC through EBUS‐TBNA was a significant independent prognostic factor for patients with HNC who had received prior treatment. Conclusions: Endobronchial ultrasound‐guided transbronchial needle aspiration is a safe, effective, and minimally invasive procedure for assessing suspected intrathoracic metastasis in HNC patients after treatment. The intrathoracic metastasis detected by EBUS‐TBNA has crucial prognostic significance in previously treated HNC patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the application value of contrast‐enhanced ultrasonography (CEUS) in ultrasound‐guided lauromacrogol injections in patients with cesarean scar pregnancies (CSP). Methods: A total of 31 patients diagnosed with CSP, who underwent an ultrasound‐guided lauromacrogol injection + curettage in our hospital between February 2019 and December 2020 and had a complete recovery confirmed by a postoperative ultrasound review and serum β‐human chorionic gonadotropin (β‐hCG) assay, were enrolled as the study subjects. According to the volume of intraoperative blood loss and the duration of postoperative vaginal bleeding, the patients were divided into two groups, with 19 in the significantly effective group (Group A) and 12 in the effective group (Group B). The recorded clinical data, including age, duration of amenorrhea, number of pregnancies, number of deliveries, time since last cesarean delivery, number of cesarean deliveries, and preoperative serum β‐hCG levels, were retrospectively analyzed. The morphological indicators in CEUS before the lauromacrogol injection, as well as immediately and 12–24 hours after the injection, were compared between the groups. Results: In Group A, the post‐injection CEUS showed no enhancement, single strip enhancement, and sparse punctate enhancement, while in Group B, it showed a more irregular ring and local patch enhancement. In addition, the number of cases where the CEUS showed no enhancement 12–24 hours after the injection was more than that of the immediate CEUS after the injection. In Group A, four (21.1%) cases showed a single strip‐like blood flow on the immediate postoperative CEUS, four (21.1%) cases showed a sparsely dotted blood flow on the immediate postoperative CEUS, and three cases turned into no enhancement 12–24 hours after the injection. A total of four cases in Group B showed that the contrast enhancement range 12–24 hours after the injection was reduced compared with that of the immediate contrast after the injection. Conclusion: Contrast‐enhanced ultrasonography can guide the location selection of the lauromacrogol injection in patients with CSP, and its postoperative morphological indicators can adequately predict the therapeutic effect after curettage and guide clinical management. [ABSTRACT FROM AUTHOR]

Methyl 7,7′-dimethoxy-5′-(morpholinomethyl)-[4,4′-bibenzo[d][1,3] dioxole]-5-carboxylate methanesulfonate (IMM) is an innovative drug for the treatment of nonalcoholic fatty liver disease (NAFLD) owing to its high efficacy and low toxicity. In this study, five minor impurities (I, II, III, IV, and V) were identified and analyzed using spectroscopic evidence, chemical synthetic methods, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The impurities included hydrolysates and oxidation by-products extracted from both the drug in its final formulation and during synthesis. Toxicity prediction revealed potential carcinogenicity of impurity V containing an N-oxygen fragment. A reliable and selective HPLC method for the quantitative analysis of impurities I–IV and a sensitive HPLC-MS/MS method for potential genotoxic impurity V were developed and optimized. The methods were validated based on the International Council for Harmonization guidelines. Satisfactory linearity was obtained for the analytes over the range of 0.1–2.0 μg/mL for impurities I–IV and 0.3–30.0 ng/mL for impurity V, and in all cases, the fitting correlation coefficients exceeded 0.999. The obtained limits of detection values were 0.05 ng/mL and 0.005 μg/mL for impurity V and impurities I–IV, respectively. The precision and repeatability of the methods were less than 1.08% and 8.72% for each impurity. The recovery percentages of all impurities were in the range of 91.18%–111.27%, with the relative standard deviation of less than 3.69%. The greenness assessment of the HPLC method and the HPLC-MS/MS method were evaluated by using AGREE software with a score value of 0.72 and 0.68, respectively. The recommended procedures that were accurate, specific, and ecofriendly were applied to the existing active pharmaceutical ingredients of IMM, and they generated satisfactory results. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is one of the most prevalent pathological kinds of lung cancer, which is a common form of cancer that has a high death rate. Over the past several years, growing studies have indicated that GPD1L was involved in the advancement of a number of different cancers. However, its clinical significance in LUAD has not been investigated. In this study, following an examination of the TGCA datasets, we found that GPD1L displayed a dysregulated state in a wide variety of cancers; this led us to believe that GPD1L is an essential regulator in the progression of malignancies. In addition, we found that the expression of GPD1L was much lower in LUAD tissues when compared with nontumor specimens. According to the findings of ROC tests, GPD1L was able to effectively identify LUAD specimens from nontumor samples with an AUC value of 0.828 (95% confidence interval: 0.793 to 0.863). On the basis of the clinical study, a low expression of GPD1L was clearly related with both the N stage and the clinical stage. Moreover, based on the findings of a Kaplan-Meier survival study, elevated GPD1L expression was a strong indicator of considerably improved overall survival (OS) and disease-specific survival (DSS). GPD1L expression and clinical stages were found to be independent prognostic indicators for overall survival and disease-free survival in LUAD patients, according to multivariate analyses. Based on multivariate analysis, the C-indexes and calibration plots of the nomogram demonstrated an effective prediction performance for LUAD patients. Besides, the expression of GPD1L was positively related to mast cells, eosinophils, Tcm, TFH, iDC, DC, and macrophages, while negatively associated with Th2 cells, NK CD56dim cells, Tgd, Treg, and neutrophils. Finally, qRT-PCR was able to demonstrate that GPD1L had a significant amount of expression in LUAD. Additionally, according to the results of functional tests, overexpression of GPD1L had a significant inhibiting effect on the proliferation of LUAD cells. In general, the results of our study suggested that GPD1L had the potential to serve as a diagnostic and prognostic marker for LUAD. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) under hypoxic conditions and drug resistance in chemotherapy are perplexing problems in anti‐tumor treatment. In addition, central nervous system neoplasm‐targeted nanoplatforms are urgently required. To address these issues, a new multi‐functional protein hybrid nanoplatform is designed, consisting of transferrin (TFR) as the multicategory solid tumor recognizer and hemoglobin for oxygen supply (ODP‐TH). This protein hybrid framework encapsulates the photosensitizer protoporphyrin IX (PpIX) and chemotherapeutic agent doxorubicin (Dox), which are attached by a glutathione‐responsive disulfide bond. Mechanistically, ODP‐TH crosses the blood–brain barrier (BBB) and specifically aggregated in hypoxic tumors via protein homology recognition. Oxygen and encapsulated drugs ultimately promote a therapeutic effect by down‐regulating the abundance of multidrug resistance gene 1 (MDR1) and hypoxia‐inducible factor‐1‐α (HIF‐1α). The results reveal that ODP‐TH achieves oxygen transport and protein homology recognition in the hypoxic tumor occupation. Indeed, compared with traditional photodynamic chemotherapy, ODP‐TH achieves a more efficient tumor‐inhibiting effect. This study not only overcomes the hypoxia‐related inhibition in combination therapy by targeted oxygen transport but also achieves an effective treatment of multiple tumors, such as breast cancer and glioma, providing a new concept for the construction of a promising multi‐functional targeted and intensive anti‐tumor nanoplatform. [ABSTRACT FROM AUTHOR]

Distant metastasis remains the major cause of morbidity for breast cancer. Individuals with liver or brain metastasis have an extremely poor prognosis and low response rates to anti‐PD‐1/L1 immune checkpoint therapy compared to those with metastasis at other sites. Therefore, it is urgent to investigate the underlying mechanism of anti‐PD‐1/L1 resistance and develop more effective immunotherapy strategies for these patients. Using single‐cell RNA sequencing, a high‐resolution map of the entire tumor ecosystem based on 44 473 cells from breast cancer liver and brain metastases is depicted. Identified by canonical markers and confirmed by multiplex immunofluorescent staining, the metastatic ecosystem features remarkable reprogramming of immunosuppressive cells such as FOXP3+ regulatory T cells, LAMP3+ tolerogenic dendritic cells, CCL18+ M2‐like macrophages, RGS5+ cancer‐associated fibroblasts, and LGALS1+ microglial cells. In addition, PD‐1 and PD‐L1/2 are barely expressed in CD8+ T cells and cancer/immune/stromal cells, respectively. Interactions of the immune checkpoint molecules LAG3‐LGALS3 and TIGIT‐NECTIN2 between CD8+ T cells and cancer/immune/stromal cells are found to play dominant roles in the immune escape. In summary, this study dissects the intratumoral heterogeneity and immunosuppressive microenvironment in liver and brain metastases of breast cancer for the first time, providing insights into the most appropriate immunotherapy strategies for these patients. [ABSTRACT FROM AUTHOR]

Low‐dielectric‐constant polymer materials are widely used in the electronic industry owing to their unique characteristics. Benzocyclobutene (BCB) resin is one such material with excellent dielectric properties and thermal stabilities. In this work, a novel BCB‐functionalized monomer (DCPDNO‐BCB) was synthesized from 2,6‐dimethyl phenol‐DCPD novolac (DCPDNO) and 4‐Bromobenzocyclobutene through Ullmann coupling. The structure of DCPDNO‐BCB was characterized by 1H NMR, 13C NMR, and ESI‐MS, and poly(DCPDNO‐BCB), obtained by ring‐opening and subsequent Diels–Alder reaction at the appropriate temperature, was found to exhibit low dielectric properties (k = 2.53 at 10 MHz), low water absorption, high thermal stability (Td5 = 430°C), and good film flatness. [ABSTRACT FROM AUTHOR]

Summary: The meroterpenoid hyperforin is responsible for the antidepressant activity of St John's wort extracts, but the genes controlling its biosynthesis are unknown.Using genome mining and biochemical work, we characterize two biosynthetic gene clusters (BGCs) that encode the first three steps in the biosynthesis of hyperforin precursors.The findings of syntenic and phylogenetic analyses reveal the parallel assembly of the two BGCs. The syntenous BGC in Mesua ferrea indicates that the first cluster was assembled before the divergence of the Hypericaceae and Calophyllaceae families. The assembly of the second cluster is the result of a coalescence of genomic fragments after a major duplication event. The differences between the two BGCs – in terms of gene expression, response to methyl jasmonate, substrate specificity and subcellular localization of key enzymes – suggest that the presence of the two clusters could serve to generate separate pools of precursors.The parallel assembly of two BGCs with similar compositions in a single plant species is uncommon, and our work provides insights into how and when these gene clusters form. Our discovery helps to advance our understanding of the evolution of plant specialized metabolism and its genomic organization. Additionally, our results offer a foundation from which hyperforin biosynthesis can be more fully understood, and which can be used in future metabolic engineering applications. [ABSTRACT FROM AUTHOR]

The orbital operation of spacecraft can excite the long-drawn and low-frequency vibration of the solar array, which is prone to affecting the task execution of the system. To address this issue, an envelope-based variable-gain control strategy is proposed to suppress vibration of the solar array using the reaction wheel (RW) actuator. The RW actuator is individually mounted on the solar array to provide reaction torque through the speed change of its rotor. The governing equation of motion of the solar array actuated by a RW actuator is deduced with the state space representation. The control relation between the measured bending moment and the rotational speed of the RW actuator with the constant-gain coefficient is firstly developed and demonstrated in numerical simulation. Changing the gain coefficient to be inversely proportional to the envelope function of vibration, a variable-gain control strategy is proposed to improve the damping effect of the RW actuator. Simulation results show that the vibration suppression performance of the RW actuator is improved compared to the constant-gain control. As the actual on-orbit natural frequency of the solar array is not always exactly known, the robustness of the control system is analyzed for the deviation between the estimated and the actual natural frequency values. The proposed variable-gain control is also experimentally verified using a simplified elastic plate model. Experimental results indicate that the vibration attenuation time is decreased to 29.1% and 50.22% compared to the uncontrolled and the constant-gain controlled states, respectively. [ABSTRACT FROM AUTHOR]

A benzocyclobutene (BCB) monomer containing carbosilane (CS‐BCB) was successfully synthesized from 4‐vinyl benzocyclobutene (4‐VBCB) and 3,6‐bis(dimethylsilyl)benzocyclobutene (3,6‐D(DMHS)BCB) by hydrosilylation in the presence of Karstedt's catalyst. As an improvement to the conventional synthesis method, the carbosilane is obtained in only two steps. In addition, this method avoids the use of halogens and Grignard reagents, which are expensive and environmentally damaging. After ring‐opening polymerization, the resultant cured CS‐BCB resin shows excellent thermal and dielectric properties; specifically, the 5 % weight loss temperature (T5%) is 435 °C, the dielectric constant (Dk) is 2.36, and the dielectric loss (Df) is less than 10−3 at 10 MHz. Thus, this polymer has enormous potential as a high‐performance electronic interlayer material. [ABSTRACT FROM AUTHOR]

In order to verify the applicability of the erythrocyte fragility test (EFT) carried out by the new fully automatic erythrocyte permeability fragility analyzer RA-800 for thalassemia screening, a total of 100 cases of suspected thalassemia patients who underwent pregnancy examinations at Luohu District People's Hospital are included. The results of a new automatic erythrocyte permeability fragility analyzer RA-800 are compared with the results of the detection system composing of the KOFA erythrocyte fragility test kit currently used in clinical laboratories. The diagnosis confirmed by genetic testing is used as the gold standard to evaluate the applicability of RA-800. The sensitivity, specificity, and accuracy of the new automatic erythrocyte permeability fragility analyzer RA-800 screening for thalassemia were 66.67%, 92.86%, and 85.00%. The KOFA direct colorimetries are 76.67%, 81.43%, and 80.00%. The kappa value for the screening of thalassemia was 0.558, which concludes that the consistency was moderate. The ROC curve indicates that both two methods had diagnostic significance for the diagnostic value of thalassemia. The new automatic erythrocyte permeability fragility analyzer RA-800 is suitable for thalassemia screening, and the performance indexes meet the clinical requirements. [ABSTRACT FROM AUTHOR]

Elastic scaling in response to changes on demand is a main benefit of serverless computing. When bursty workloads arrive, a serverless platform launches many new containers and initializes function environments (known as cold starts), which incurs significant startup latency. To reduce cold starts, platforms usually pause a container after it serves a request, and reuse this container for subsequent requests. However, this reuse strategy cannot efficiently reduce cold starts because the schedulers are agnostic of container lifecycle. For example, it may ignore soon available containers or evict soon needed containers. We propose a container lifecycle‐aware scheduling strategy for serverless computing, CAS. The key idea is to control distribution of requests and determine creation or eviction of containers according to different lifecycle phases of containers. We implement a prototype of CAS on OpenWhisk. Our evaluation shows that CAS reduces 81% cold starts and therefore brings a 63% reduction at 95th percentile latency compared with native scheduling strategy in OpenWhisk when there is worker contention between workloads, and does not add significant performance overhead. [ABSTRACT FROM AUTHOR]

(B) The docking-derived agonists discovered by Fink et al.,[5] like '9087 and PS75, preferentially activate Gi/o/z G protein subtypes without engagement of -arrestins, separating analgesic properties from sedation gl Some principles of drug development strategies could be distilled from this most updated study. Early attempts were made with conventional concepts, including modifying the existing validated analgesic drugs, changing the administration route and combination medication. Structure-based drug discovery facilitates future painkiller development. [Extracted from the article]

Ewing sarcoma (ES) is one of the most aggressive types of pediatric tumors. The lack of tools for the identification of ES has largely hindered clinical diagnosis and the improvement of treatment. To address this challenge, we synthesized a near‐infrared (NIR) fluorescent probe (CS2‐N‐E9R) that targets the ES‐specific fusion protein EWS–FLI1 (E/F). This probe exhibited specific and high binding affinity to E/F. Further studies in animal models showed that CS2‐N‐E9R can be used to identify the boundaries of ES and lymph node metastases under a complex biological environment. These results demonstrate that CS2‐N‐E9R is a promising probe for early diagnosis and surgical guidance of ES through molecularly targeted NIR imaging. [ABSTRACT FROM AUTHOR]

The coloration and hatchability of insect eggs can affect individual and population survival. However, few genetic loci have been documented to affect both traits, and the genes involved in regulating these two traits are unclear. The silkworm recessive mutant rel shows both red egg color and embryo mortality. We studied the molecular basis of the rel phenotype formation. Through genetic analysis, gene screening and sequencing, we found that two closely linked genes, BGIBMGA003497 (Bm‐re) and BGIBMGA003697 (BmSema1a), control egg color and embryo mortality, respectively. Six base pairs of the Bm‐re gene are deleted in its open reading frame, and BmSema1a is expressed at abnormally low levels in mutant rel. BmSema1a gene function verification was performed using RNA interference and clustered randomly interspersed palindromic repeats (CRISPR)/CRISPR‐associate protein 9. Deficiency of the BmSema1a gene can cause the death of silkworm embryos. This study revealed the molecular basis of silkworm rel mutant formation and indicated that the Sema1a gene is essential for insect embryo development. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) causes neurotransmitter release, oligemia, membrane depolarization, mitochondrial dysfunction, and results in the high rate of mortality and functional disability. Here, we focus on PTEN‐induced kinase 1 (PINK1), a mitochondrial‐targeted protein kinase, and explore its role in ICH progression. Methods: The qPCR and Western blot were performed to examine the expression of PINK1 in ICH patients and mouse model. PINK1 gain‐ and loss‐of‐function mice were used to evaluate their protective role on brain injury and behavioral disorders. Flow cytometry was carried out, mitochondrial membrane potential and reactive oxygen species production were detected to explore the distribution and neuroprotective function of PINK1. Results: PINK1 mRNA was upregulated, however, its protein was downregulated in ICH patients. The reduction of PINK1 was mainly happened in microglial cells in ICH model. Overexpression of PINK1 is able to rescue ICH‐induced behavioral disorders. PINK1 protects ICH‐induced brain injury by promoting mitochondrial autophagy in microglia. Conclusion: PINK1 possesses a neuroprotective role and antagonizes ICH by promoting mitochondrial autophagy, which may be of value as a therapeutic target for ICH treatment. [ABSTRACT FROM AUTHOR]

Artesunate is a widely used derivative of artemisinin for malaria. Recent researches have shown that artesunate has a significant anti‐inflammatory effect on many diseases. However, its effect on acute kidney injury with a significant inflammatory response is not clear. In this study, we established a cisplatin‐induced AKI mouse model and a co‐culture system of BMDM and tubular epithelial cells (mTEC) to verify the renoprotective and anti‐inflammatory effects of artesunate on AKI, and explored the underlying mechanism. We found that artesunate strongly down‐regulated the serum creatinine and BUN levels in AKI mice, reduced the necroptosis of tubular cells and down‐regulated the expression of the tubular injury molecule Tim‐1. On the other hand, artesunate strongly inhibited the mRNA expression of inflammatory cytokines (IL‐1β, IL‐6 and TNF‐α), protein levels of inflammatory signals (iNOS and NF‐κB) and necroptosis signals (RIPK1, RIPK3 and MLKL) in kidney of AKI mouse. Notably, the co‐culture system proved that Mincle in macrophage can aggravate the inflammation and necroptosis of mTEC induced by LPS, and artesunate suppressed the expression of Mincle in macrophage of kidney in AKI mouse. Overexpression of Mincle in BMDM restored the damage and necroptosis inhibited by artesunate in mTEC, indicating Mincle in macrophage is the target of artesunate to protect tubule cells in AKI. Our findings demonstrated that artesunate can significantly improve renal function in AKI, which may be related to the inhibition of Mincle‐mediated macrophage inflammation, thereby reducing the damage and necroptosis to tubular cells that provide new option for the treatment of AKI. [ABSTRACT FROM AUTHOR]

Polo‐like kinase 4 (PLK4) has been reported to contribute to tumor growth, invasion, and metastasis. However, the role of PLK4 in human bladder cancer (BC) remains unclear. Here, we demonstrate the regulatory function of PLK4 in human BC progression. PLK4 is overexpressed in BC cell lines and tissues, and its overexpression correlated with poor prognosis. Our transcriptome analysis combined with subsequent functional assays indicated that PLK4 inhibition can suppress BC cell growth and induce cell cycle arrest at G1 phase via activation of the p38/p53/p21 pathway in vitro and in vivo. Overall, our data suggest that PLK4 is a critical regulator of BC cell proliferation, and thus, it may have potential as a novel molecular target for BC treatment. [ABSTRACT FROM AUTHOR]

Objectives: Graft patency and completeness of revascularization were analyzed in patients who underwent off‐pump minimally invasive coronary artery bypass grafting via a left small thoracotomy. Methods: We retrospectively reviewed the invasive angiography findings and clinical data of 186 consecutive patients who underwent off‐pump minimally invasive coronary artery bypass grafting via a left small thoracotomy. The left internal thoracic artery and saphenous vein were used to bypass two or more of three coronary artery systems: the left anterior descending artery, left circumflex artery, or right coronary artery. Before hospital discharge, invasive angiography was performed to assess graft patency. Clinical variables during hospitalization and follow‐up were collected and analyzed. Results: All 186 patients successfully underwent off‐pump minimally invasive coronary artery bypass grafting without conversion to sternotomy or assistance of cardiopulmonary bypass. The mean graft number was 2.81 per patient (range, 2–5), and the total number of grafts was 522. The in‐hospital mortality rate was 1.6% (3 of 186). A total of 181 of 186 (97.3%) patients underwent postoperative invasive angiography. Among the 510 grafts assessed by angiography, the total graft patency rate was 96.3% (491 of 510) (98.3% [171 of 174] for left internal thoracic artery grafts and 95.2% [318 of 334] for saphenous vein grafts). The rate of complete revascularization was 99.5% (185 of 186). Conclusions: Minimally invasive coronary artery bypass grafting using left internal thoracic artery and saphenous vein grafts provides acceptable graft patency and completeness of revascularization for selected patients with multivessel disease. [ABSTRACT FROM AUTHOR]

Environmental issues are some of the most pressing threats the world is facing nowadays. In this context, motivating individual pro‐environmental behavior becomes highly relevant. One strategy is to harness people's pro‐environmental dispositions (e.g., biospheric values, pro‐environmental attitudes). Although acknowledging the need to behave pro‐environmentally lies at the core of these dispositions, the extent to which they are reflected in day‐to‐day pro‐environmental practices fluctuates to a great extent. How to bridge this gap between dispositions and behaviors in pro‐environmentalism? This research tests a novel psychological solution, that is, to heighten subjective feelings of power. Power depicts people's control over their own and others' outcomes. Two studies (total N = 338, with n = 200 in Study 1 and n = 138 in Study 2) manipulated people's situational sense of high versus low power (by recalling and writing about relevant incidents), measured pro‐environmental dispositions (biospheric values in Studies 1 and 2; attitude toward a specific environmental cause in Study 2), and examined their effects on pro‐environmental behaviors (spending time on environmental persuasion in Study 1 and spending money on environmental donation in Study 2). Overall, both studies revealed that pro‐environmental dispositions predicted pro‐environmental behaviors, but only when the actors were prompted to experience a high instead of a low sense of power. The findings illuminate power as an important and viable communication tactic—to orient people toward their dispositions and practice what they preach in pro‐environmentalism. [ABSTRACT FROM AUTHOR]

Histone deacetylase 3 (HDAC3) is a potential drug target for treatment of human diseases such as cancer, chronic inflammation, neurodegenerative diseases and diabetes. Machine learning (ML) as an essential cheminformatics approach has been widely used for QSAR modeling. However, none of them has been applied to HDAC3. To this end, we carefully compiled a set of 1098 compounds from the ChEMBL database that have been assayed against HDAC3 and calculated three different sets of molecular features for each compound, i. e. two‐dimensional Mordred descriptors, MACCS keys (166 bits) and Morgan2 fingerprints (1024 bits). Five ML classifiers, i. e. k‐Nearest Neighbour (KNN), Support Vector Machine (SVM), Random forest (RF), eXtreme Gradient Boosting (XGBoost) and Deep Neural Network (DNN) were trained on each feature set and optimized for classification. A total of 15 models were generated and carefully compared, among which the best‐performing one was the XGBoost model based on the Morgan2 fingerprints, i. e. XGBoost_morgan2. Evaluated on a well‐curated benchmarking set named MUBD‐HDAC3, this model achieved a high early ROC enrichment (ROCE0.5 %: 41.02). A further retrospective screening of an annotated chemical library in PubChem demonstrated that the best model could identify 8 novel‐scaffold HDAC3 inhibitors while assaying only 1 % of the compounds. To make this model accessible for the scientific community, we developed a python GUI application named HDAC3i‐Finder to facilitate prospective screening for HDAC3 inhibitors. The source code of HDAC3i‐Finder is available at https://github.com/jwxia2014/HDAC3i‐Finder. [ABSTRACT FROM AUTHOR]

Subtrochanteric osteotomy of the femur (STO) is a valuable corrective procedure in hip surgeries. However, STO in traditional posterolateral approach usually encounters complications such as postoperative dislocation, bone non‐union, and prosthesis failure. Some relevant pathologies and mechanisms have been identified, but there is sparse evidence for verification. The aim of this video in orthopaedic technique is to test our hypothesis of STO in direct anterior approach to total hip arthroplasty in a complicated hip surgery, and to further illustrate the rationality, reproducibility, and superiority of STO in this minimally invasive and enhanced‐recovery approach by presenting a standardized and systemic protocol, as well as operational pearls and pitfalls. [ABSTRACT FROM AUTHOR]

Inhibition of the aberrant Wnt pathway is a promising approach for the treatment of various types of disease. Based on the previous SAR results, we continued to optimize the structure of the dicarboximide‐phenylpyridine conjugates as the Wnt pathway inhibitors. Two cis‐4‐cyclohexene‐1, 2‐dicarboximide derivatives 6 and 16 showed much better wnt inhibitory activity than that of the lead compound among the eighteen novel compounds. The IC50 of the most potent compound 16 was 30 nM, which was about 10‐folds more potent than the lead compound 1 b, and 100‐folds more potent than the hit compound 1 a. Although the compounds have similar structure with tankyrases inhibitor IWR‐1 series compounds, they did not inhibit tankyrase 1/2, indicating they had different mechanism. [ABSTRACT FROM AUTHOR]