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Abstract Background Abnormal lipid metabolism has recently been reported as a crucial signature of idiopathic pulmonary fibrosis (IPF). However, the origin and biological function of the lipid and possible mechanisms of increased lipid content in the pathogenesis of IPF remains undetermined. Methods Oil-red staining and immunofluorescence analysis were used to detect lipid accumulation in mouse lung fibrosis frozen sections, Bleomycin-treated human type II alveolar epithelial cells (AECIIs) and lung fibroblast. Untargeted Lipid omics analysis was applied to investigate differential lipid species and identified LysoPC was utilized to treat human lung fibroblasts and mice. Microarray and single-cell RNA expression data sets identified lipid metabolism-related differentially expressed genes. Gain of function experiment was used to study the function of 3-hydroxy-3-methylglutaryl-Coa Synthase 2 (HMGCS2) in regulating AECIIs lipid metabolism. Mice with AECII-HMGCS2 high were established by intratracheally delivering HBAAV2/6-SFTPC- HMGCS2 adeno-associated virus. Western blot, Co-immunoprecipitation, immunofluorescence, site-directed mutation and flow cytometry were utilized to investigate the mechanisms of HMGCS2-mediated lipid metabolism in AECIIs. Results Injured AECIIs were the primary source of accumulated lipids in response to Bleomycin stimulation. LysoPCs released by injured AECIIs could activate lung fibroblasts, thus promoting the progression of pulmonary fibrosis. Mechanistically, HMGCS2 was decreased explicitly in AECIIs and ectopic expression of HMGCS2 in AECIIs using the AAV system significantly alleviated experimental mouse lung fibrosis progression via modulating lipid degradation in AECIIs through promoting CPT1A and CPT2 expression by interacting with PPARα. Conclusions These data unveiled a novel etiological mechanism of HMGCS2-mediated AECII lipid metabolism in the genesis and development of pulmonary fibrosis and provided a novel target for clinical intervention.

Exposure to environmental carcinogens is a significant contributor to cancer development, with genetic and epigenetic alterations playing pivotal roles in the carcinogenic process. However, the interplay between epigenetic regulation and genetic changes in carcinogenesis has yet to receive comprehensive attention. This study investigates the impact of continuous exposure to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on bronchial epithelial cells, leading to malignant transformation. Our findings reveal the down-regulation of the tumor suppressor-like circular RNA circNIPBL during oncogenic processes concomitant with the accumulation of the TP53-H179R, a single nucleotide variant. Diminished circNIPBL expression enhances the proliferative, distant metastatic, and tumor-forming capabilities of NNK-induced cancerous cells and lung cancer cell lines (A549, H1299), while also promoting the accumulation of TP53-H179R during NNK-induced carcinogenesis. Mechanistic investigations demonstrate that circNIPBL interacts with HSP90α to regulate the translocation of AHR into the nucleus, which may be a potential regulatory mechanism for NNK-induced carcinogenesis and TP53-H179R accumulation. This study introduces a novel perspective on the interplay between genetic alterations and epigenetic regulation in chemical carcinogenesis, which provides novel insight into the etiology of cancer.

Disturbances in copper (Cu) homeostasis have been observed in diabetes and associated complications. Cu is an essential micronutrient that plays important roles in various fundamental biological processes. For example, diabetic cardiomyopathy is associated with elevated levels of Cu in the serum and tissues. Therefore, targeting Cu may be a novel treatment strategy for diabetic complications. This review provides an overview of physiological Cu metabolism and homeostasis, followed by a discussion of Cu metabolism disorders observed during the occurrence and progression of diabetic complications. Finally, we discuss the recent therapeutic advances in the use of Cu coordination complexes as treatments for diabetic complications and their potential mechanisms of action. This review contributes to a complete understanding of the role of Cu in diabetic complications and demonstrates the broad application prospects of Cu-coordinated compounds as potential therapeutic agents.

Abstract Heterogeneous organ‐specific responses to immunotherapy exist in lung cancer. Dissecting tumor microenvironment (TME) can provide new insights into the mechanisms of divergent responses, the process of which remains poor, partly due to the challenges associated with single‐cell profiling using formalin‐fixed paraffin‐embedded (FFPE) materials. In this study, single‐cell nuclei RNA sequencing and imaging mass cytometry (IMC) are used to dissect organ‐specific cellular and spatial TME based on FFPE samples from paired primary lung adenocarcinoma (LUAD) and metastases. Single‐cell analyses of 84 294 cells from sequencing and 250 600 cells from IMC reveal divergent organ‐specific immune niches. For sites of LUAD responding well to immunotherapy, including primary LUAD and adrenal gland metastases, a significant enrichment of B, plasma, and T cells is detected. Spatially resolved maps reveal cellular neighborhoods recapitulating functional units of the tumor ecosystem and the spatial proximity of B and CD4+ T cells at immunogenic sites. Various organ‐specific densities of tertiary lymphoid structures are observed. Immunosuppressive sites, including brain and liver metastases, are deposited with collagen I, and T cells at these sites highly express TIM‐3. This study originally deciphers the single‐cell landscape of the organ‐specific TME at both cellular and spatial levels for LUAD, indicating the necessity for organ‐specific treatment approaches.

C15H25KN4O10, monoclinic, P21 (no. 4), a = 8.3669(3) Å, b = 13.6610(4) Å, c = 9.6179(3) Å, β = 104.578(1)°, V = 1063.94(6) Å3, Z = 2, Rgt(F) = 0.0391, wRref(F2) = 0.0863, T = 150 K.

Abstract We present a user-friendly molecular generative pipeline called Pocket Crafter, specifically designed to facilitate hit finding activity in the drug discovery process. This workflow utilized a three-dimensional (3D) generative modeling method Pocket2Mol, for the de novo design of molecules in spatial perspective for the targeted protein structures, followed by filters for chemical-physical properties and drug-likeness, structure–activity relationship analysis, and clustering to generate top virtual hit scaffolds. In our WDR5 case study, we acquired a focused set of 2029 compounds after a targeted searching within Novartis archived library based on the virtual scaffolds. Subsequently, we experimentally profiled these compounds, resulting in a novel chemical scaffold series that demonstrated activity in biochemical and biophysical assays. Pocket Crafter successfully prototyped an effective end-to-end 3D generative chemistry-based workflow for the exploration of new chemical scaffolds, which represents a promising approach in early drug discovery for hit identification.

Abstract Background The paucity of reliable biomarkers for predicting immunotherapy efficacy in patients with advanced hepatocellular carcinoma (HCC) has emerged as a burgeoning concern with the expanding use of immunotherapy. This study endeavors to delve into the potential peripheral biomarkers capable of prognosticating efficacy in HCC patients who are poised to receive anti-PD-1 monotherapy within the phase III clinical trial, KEYNOTE394. Additionally, we sought to elucidate the underlying molecular mechanisms for resistance to immune checkpoint blockade (ICB) and propose innovative combination immunotherapy strategies for future clinical application. Methods Patient blood samples were collected for single-cell RNA sequencing to evaluate the immune cell signature before receiving ICB therapy. Subsequently, in vitro assays and in vivo murine model experiments were conducted to validate the mechanism that S100A9+CD14+ monocytes play a role in ICB resistance. Results Our study demonstrates a notable enrichment of S100A9+CD14+ monocytes in the peripheral blood of patients exhibiting suboptimal responses to anti-PD-1 therapy. Moreover, we identified the Mono_S100A9 signature as a predictive biomarker, indicative of reduced efficacy in immunotherapy and decreased survival benefits across various tumor types. Mechanistically, S100A9 activates PD-L1 transcription by directly binding to the CD274 (PD-L1) gene promoter, thereby suppressing T-cell proliferation and cytotoxicity via the PD-1/PD-L1 axis, consequently diminishing the therapeutic effectiveness of subsequent anti-PD-1 treatments. Furthermore, our in vivo studies revealed that inhibiting S100A9 can synergistically enhance the efficacy of anti-PD-1 drugs in the eradication of hepatocellular carcinoma. Conclusions Our study underscores the significance of S100A9+CD14+ monocytes in predicting inadequate response to ICB treatment and provides insights into the monocyte cell-intrinsic mechanisms of resistance to ICB therapy. We also propose a combined therapeutic approach to enhance ICB efficacy by targeting S100A9.

Vitamin K2 (MK-7) has been shown to cause significant changes in different physiological processes and diseases, but its role in acute lung injury (ALI) is unclear. Therefore, in this study, we aimed to evaluate the protective effects of VK2 against LPS-induced ALI in mice. The male C57BL/6J mice were randomly divided into six groups (n = 7): the control group, LPS group, negative control group (LPS + Oil), positive control group (LPS + DEX), LPS + VK2 (L) group (VK2, 1.5 mg/kg), and LPS + VK2 (H) group (VK2, 15 mg/kg). Hematoxylin–eosin (HE) staining of lung tissue was performed. Antioxidant superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, and the Ca2+ level in the lung tissue were measured. The effects of VK2 on inflammation, apoptosis, tight junction (TJ) injury, mitochondrial dysfunction, and autophagy were quantitatively assessed using Western blot analysis. Compared with the LPS group, VK2 improved histopathological changes; alleviated inflammation, apoptosis, and TJ injury; increased antioxidant enzyme activity; reduced Ca2+ overload; regulated mitochondrial function; and inhibited lung autophagy. These results indicate that VK2 could improve tight junction protein loss, inflammation, and cell apoptosis in LPS-induced ALI by inhibiting the mitochondrial dysfunction and excessive autophagy, indicating that VK2 plays a beneficial role in ALI and might be a potential therapeutic strategy.

Abstract In the field of world heritage conservation, there has been broad consensus on carrying out heritage conservation research on the basis of spatial integration and interregional and international cooperation. However, there are still many deficiencies in the integration of culture with the environment, regional economic and social development, and the regional, holistic and multimodal conservation and utilization of cultural heritage sites. In China, the Dongjiang-Hanjiang River Basin is a representative area of substantial cultural and ecological value for both Guangdong Province and the whole country. This paper uses the morphological spatial pattern analysis and the minimum cumulative resistance model to integrate cultural ecology sources and establish a cross-regional and large-scale cultural ecology network system that includes 1 main corridor, 22 important corridors and 17 secondary corridors. In addition, based on identified cultural landscape nodes and cultural ecology services, the economy of the cultural ecology corridor could be developed with large-scale co-construction, co-governance and shared working mechanisms to overcome administrative limits and realize the conservation and utilization of multimodal and large-scale heritage sites. This approach has strong theoretical and practical significance for innovative methods in cultural ecology research, as well as for new content in the research of Lingnan culture, ecosystem restoration, and the economic and social development of towns and villages. This article supplements unilateral studies of regional culture and ecology and demonstrates an in-depth application of cultural ecology theory.

Abstract Sensitive and stable perovskite X-ray detectors are attractive in low-dosage medical examinations. The high sensitivity, tunable chemical compositions, electronic dimensions, and low-cost raw materials make perovskites promising next-generation semiconductors. However, their ionic nature brings serious concerns about their chemical and water stability, limiting their applications in well-established technologies like crystal polishing, micro-processing, photolithography, etc. Herein we report a one-dimensional tryptamine lead iodide perovskite, which is stable in water for several months as the strong cation-π interactions between organic cations. The one-dimensional and two-dimensional tryptamine lead iodide perovskite tablets are switchable through thermal-annealing or water-soaking treatments to relax microstrains. The water-stable and microstrain-free one-dimensional perovskite tablets yield a large sensitivity of 2.5 × 106 μC Gyair −1 cm−2 with the lowest detectable dose rate of 5 nGyair s−1. Microelectrode arrays are realized by surface photolithography to construct high-performance X-ray flat mini-panels with good X-ray imaging capability, and a record spatial resolution of 17.2 lp mm−1 is demonstrated.

Background: To investigate the expression levels and diagnostic value of glial cell line-derived neurotrophic factor (GDNF), carcinoembryonic antigen (CEA) and carbohydrate antigen199 (CA199) in patients with colorectal carcinoma (CRC). Methods: 50 CRC patients at our hospital from Feb. 2020 to Feb. 2021 were chosen as the malignant group, another 50 patients with benign colonic diseases were chosen as the benign group, and 50 healthy people who came to our hospital for physical examination during the same period were considered as the control group. Fasting peripheral venous blood was taken from all research subjects in the morning and tested by a fully-automated electrochemiluminometer to determine the GDNF, CEA and CA199 levels. The sensitivity and specificity of the combined detection of the three indexes for CRC were analyzed, and the receiver operating characteristic (ROC) curve was plotted to record the area under the curve (AUC). Results: The malignant group had remarkably higher CEA and CA199 levels (P

Abstract Advanced photodetectors with intelligent functions are expected to take an important role in future technology. However, completing complex detection tasks within a limited number of pixels is still challenging. Here, we report a differential perovskite hemispherical photodetector serving as a smart locator for intelligent imaging and location tracking. The high external quantum efficiency (~1000%) and low noise (10−13 A Hz−0.5) of perovskite hemispherical photodetector enable stable and large variations in signal response. Analysing the differential light response of only 8 pixels with the computer algorithm can realize the capability of colorful imaging and a computational spectral resolution of 4.7 nm in a low-cost and lensless device geometry. Through machine learning to mimic the differential current signal under different applied biases, one more dimensional detection information can be recorded, for dynamically tracking the running trajectory of an object in a three-dimensional space or two-dimensional plane with a color classification function.

This research identified four amino acid residues (Leu174, Asn297, Tyr301, and Gln291) that contribute to substrate recognition by the high-affinity glucose transporter Xltr1p from Trichoderma reesei. Potential hotspots affecting substrate specificity were selected through homology modeling, evolutionary conservation analyses, and substrate-docking modeling of Xltr1p. Variants carrying mutations at these hotspots were subsequently obtained via in silico screening. Replacement of Leu174 or Asn297 in Xltr1p with alanine resulted in loss of hexose transport activity, indicating that Leu174 and Asn297 play essential roles in hexose transport. The Y301W variant exhibited accelerated mannose transport, but lost galactose transport capacity, and mutation of Gln291 to alanine greatly accelerated mannose transport. These results suggest that amino acids located in transmembrane α-helix 7 (Asn297, Tyr301, and Gln291) play critical roles in substrate recognition by the hexose transporter Xltr1p. Our results will help expand the potential applications of this transporter and provide insights into the mechanisms underlying its function and specificity.

Acetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH2), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective effect of MgH2 against APAP-AKI. The results showed that MgH2 improved renal function and histological injury in mice of APAP-AKI. MgH2 also had protective effects on APAP-induced cytotoxicity in HK-2 cells. In addition, the increased level of reactive oxygen species (ROS) and expressions of inflammatory cytokines (TNF-α and IL-1β) and pro-apoptotic factors (Bad, Bax, Caspase3, and CytC) induced by APAP were downregulated with MgH2 treatment. Furthermore, the expressions of molecules related to TXNIP/NLRP3/NF-κB pathway (TXNIP, NLRP3, NF-κB p65 and p-NF-κB p65) in renal tissues and HK-2 cells were enhanced by APAP overdose, which were reduced by MgH2 administration. Collectively, this study indicated that MgH2 protects against APAP-AKI by alleviating oxidative stress, inflammation and apoptosis via inhibition of TXNIP/NLRP3/NF-κB signaling pathway.

Abstract The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore the impact of APOE+ macrophages on ICI therapy using single‐cell RNA sequencing (scRNA‐seq) and machine learning methods. The scRNA‐seq and bulk RNA‐seq data are Integrated to construct an M.Sig model for predicting ICI response based on the distinct molecular signatures of macrophage and machine learning algorithms. Comprehensive single‐cell analysis as well as in vivo and in vitro experiments are applied to explore the potential mechanisms of the APOE+ macrophage in affecting ICI response. The M.Sig model shows clear advantages in predicting the efficacy and prognosis of ICI therapy in pan‐cancer patients. The proportion of APOE+ macrophages is higher in ICI non‐responders of triple‐negative breast cancer compared with responders, and the interaction and longer distance between APOE+ macrophages and CD8+ exhausted T (Tex) cells affecting ICI response is confirmed by multiplex immunohistochemistry. In a 4T1 tumor‐bearing mice model, the APOE inhibitor combined with ICI treatment shows the best efficacy. The M.Sig model using real‐world immunotherapy data accurately predicts the ICI response of pan‐cancer, which may be associated with the interaction between APOE+ macrophages and CD8+ Tex cells.

Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion (I/R) injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner. Genomic deletion of a fms-intronic regulatory element (FIRE) in the Csf1r locus resulted in specific absence of resident homeostatic and antigen-presenting macrophages, without affecting the recruitment of monocyte-derived macrophages to the infarcted heart. Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodeling without influencing infarct size. In contrast, continuous CSF1R inhibition led to depletion of both resident and recruited macrophage populations. This augmented adverse remodeling after I/R and led to an increased infarct size and deterioration of cardiac function. In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodeling, while recruited macrophages determine infarct size after I/R injury. These findings attribute distinct beneficial effects to different macrophage populations in the context of myocardial infarction.

Fusarium crown rot (FCR) is an important and devastating disease of wheat (Triticum aestivum) caused by the fungus Fusarium pseudograminearum and related pathogens. Using two distinct susceptible cultivars, we investigated the isolation frequencies of F. pseudograminearum and quantified its biomass accumulation and the levels of the associated toxins deoxynivalenol (DON) and DON-3-glucoside (D3G) in inoculated field-grown wheat plants. We detected F. pseudograminearum in stem, peduncle, rachis, and husk tissues, but not in grains, whereas DON and D3G accumulated in stem, rachis, husk, and grain tissues. Disease severity was positively correlated with the frequency of pathogen isolation, F. pseudograminearum biomass, and mycotoxin levels. The amount of F. pseudograminearum biomass and mycotoxin contents in asymptomatic tissue of diseased plants were associated with the distance of the tissue from the diseased internode and the disease severity of the plant. Thus, apparently healthy tissue may harbor F. pseudograminearum and contain associated mycotoxins. This research helps clarify the relationship between F. pseudograminearum occurrence, F. pseudograminearum biomass, and mycotoxin accumulation in tissues of susceptible wheat cultivars with or without disease symptoms, providing information that can lead to more effective control measures.

Abstract Osteoporosis is a progressive bone disease caused by impaired function of endogenous bone marrow-derived mesenchymal stem cells (BMSCs). Herein, we investigated the mechanism of lncRNA SNHG14 in osteoporosis progression. BMSCs were isolated from BALB/c mice. The osteogenic ability of BMSCs was assessed by Alkaline phosphatase (ALP) and Alizarin Red S Staining (ARS) staining. The interaction between miR-493-5p and SNHG14 or myocyte enhancer factor 2 C (Mef2c) was confirmed by dual-luciferase reporter assay. Bone histomorphometry changes were evaluated to analyze SNHG14’roles in osteoporosis in vivo. Our results illustrated SNHG14 and Mef2c levels were increased in a time-dependent manner in BMSCs, and miR-493-5p expression was decreased. SNHG14 knockdown inhibited osteogenic differentiation of BMSCs, and SNHG14 upregulation had the opposite effect. SNHG14 overexpression elevated bone mineral density and bone trabecular number, and alleviated osteoporosis progression in vivo. Mechanically, miR-493-5p was a target of SNHG14, and miR-493-5p targeted the Mef2c gene directly. SNHG14 overexpression reversed the inhibition of miR-493-5p on the osteogenic ability of BMSCs, and miR-493-5p silencing accelerated BMSCs osteogenesis by activating Mef2c-mediated autophagy to accelerate BMSCs osteogenesis. In short, SNHG14 activated autophagy via regulating miR-493-5p/Mef2c axis to alleviate osteoporosis progression, which might provide a new molecular target for osteoporosis treatment.

In this study, an optimized composite was prepared based on chemically modified corn straw, chitosan, and poly(lactic acid) using Response Surface Methodology (RSM). The composite was produced by screw extruding and hot pressing. The Box Behnken Design (BBD) software was used to design the test to optimize the composite composition. The optimum ratio of 3 factors, e.g. chemically modified corn straw (0.10 to 0.40 g), chitosan (0.25 to 0.75 g), and poly(lactic acid) (2.00 to 3.00 g) on the response value (bending strength) of the composite was investigated. RSM-BBD provided the optimum combination of composites. The novel composite prepared under the optimized factors was characterized by Fourier transform infrared spectroscopy, mechanical testing, water absorption tests, contact angle tests, and scanning electron microscopy. The results showed that the mechanical strength, e.g., bending strength, impact strength, and tensile strength of chemically modified corn straw based composite were 21.6 MPa, 4.43 kJ/m2, and 20.0 MPa, respectively, which increased by 23.5%, 13.9%, and 18.7% compared to native corn straw based composite. Improved mechanical strength and hydrophobicity for chemically modified corn straw/chitosan/poly(lactic acid) demonstrated that chemically modified biomass fibers and bio-based degradable polymers have the potential to produce environmentally friendly composites.

With the continuous development of information technology, the information environment while driving is constantly being enriched, and driver information processing and application are also dynamically evolving. Analysing information processing and application can better provide information services and is particularly important for traffic safety. Based on VOSviewer bibliometric software, this paper explores the research hotspots and future development trends of the driver information processing and application fields using the Web of Science (WoS) core collection as the data source. The results show that the field has a long history and has grown steadily in recent years. The United States, China and Germany are the top three countries in terms of the number of published articles. “Situational awareness and visual load”, “route selection under variable information signs”, “en-route information and behaviour” and “new information technology attitudes” are important knowledge bases for driver information processing and application. En-route information sources, human-computer interaction, and autonomous vehicle information are the research trends of the driver information processing and application field. The results of this research can help people comprehensively and systematically understand the current situation of driver information processing and application research, provide directions for future driver information processing and application research, and promote the engineering application of such research.

Abstract The development of economical and efficient roadbed silt reinforcement technology not only guides the proficient utilization of silt resources but also fosters the green development of geotechnical engineering construction. Ensuring the robust dynamic stability of the roadbed is pivotal for the safe operation of vehicular traffic. In this context, employing recycled polyester fibers and inorganic curing agents, this paper leverages dynamic triaxial testing and scanning electron microscopy (SEM) methods to scrutinize the dynamic characteristics and microscopic mechanisms of recycled fiber polymer modified roadbed silt. The findings indicate that: (1) with a fiber content of 0.2%, the fiber-modified soil sample exhibits minimal damage, maximal dynamic strength and dynamic elastic modulus, and optimum resilience to dynamic loads; (2) akin to fiber-reinforced sand, an elevation in confining pressure can induce the creation of a quasi-cohesive force in fiber-reinforced soil, equivalently enhancing the confining pressure and thereby amplifying its strength; and (3) the surfaces of microparticles in the enhanced soil structure are enveloped with cementitious substances, while smaller soil particles coalesce to form aggregates that fill inter-particle pores, cultivating a denser and more stable improved soil structure and augmenting the dynamic characteristics of the improvement investment.

The tomato (Solanum lycopersicum L.), a widely cultivated and economically important vegetable crop, is subject to a number of biotic and abiotic stresses in nature. Several abiotic and biotic stresses have been demonstrated to elevate the concentration of cytosolic free Ca2+ ([Ca2+]i) in Arabidopsis due to the influx of calcium ions. In this study, recombinant aequorin was introduced into the tomato in order to investigate the change in [Ca2+]i when treated with exogenous Ca2+. This resulted in strong luminescence signals, which were mainly observed in the roots. Luminescence signals were also detected in the whole plant, including the leaves, when a surfactant (Silwet L-77) was added to coelenterazine. The concentration of [Ca2+]i increased with the dosage of NaCl/elf18. The luminescence signals also showed a lower increase in intensity with elf18 treatment compared to NaCl treatment. Furthermore, the [Ca2+]i responses to other abiotic or biotic stresses, such as H2O2 and Pep1, were also evaluated. It was found that this transgenic tomato expressing aequorin can effectively detect changes in [Ca2+]i levels. The transgenic tomato expressing aequorin represents an effective tool for detecting changes in [Ca2+]i and provides a solid basis for investigating the adaptation mechanisms of tomatoes to various abiotic and biotic stresses. Moreover, the aequorin-based system would be a highly valuable tool for studying the specificity and crosstalk of plant signalling networks under abiotic and biotic stresses in tomatoes.

Intensity-modulated direct-detection (IM/DD) optical systems are most widely employed in short-reach optical interconnects due to their simple structure and cost-effectiveness. However, IM/DD systems face mixed linear and nonlinear channel impairments, mainly induced by the combination of square-law detection and chromatic dispersion, as well as the utilization of low-cost non-ideal transceivers. To solve this issue, recent years have witnessed a growing trend of introducing machine learning technologies such as neural networks (NNs) into IM/DD systems for channel equalization. NNs usually present better system performance than traditional approaches, and various types of NNs have been investigated. Despite the excellent system performance, the associated high computational complexity is a major drawback that hinders the practical application of NN-based equalizers. This paper focuses on the performance and complexity trade-off of NNs employed in IM/DD systems, presenting a systematic review of the current status of NN-based equalizers as well as a number of effective complexity reduction approaches. The future trends of leveraging advanced NN in IM/DD links are also discussed.

Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but it also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg loss are key approaches for an HBV functional cure. In this study, we found that YZH-106, a rupestonic acid derivative, inhibited HBsAg secretion and viral replication. Further investigation demonstrated that YZH-106 promoted the lysosomal degradation of viral L- and M-HBs proteins. A mechanistic study using Biacore and docking analysis revealed that YZH-106 bound directly to the PreS2 domain of L- and M-HBsAg, thereby blocking their entry into the endoplasmic reticulum (ER) and promoting their degradation in cytoplasm. Our work thereby provides the basis for the design of a novel compound therapy to target HBsAg against HBV infection.

C9H8N8O8, monoclinic, P21/c (no. 14), a = 12.0387(3) Å, b = 10.7899(2) Å, c = 11.4310(3) Å, β = 111.536(3)°, V = 1,381.18(6) Å3, Z = 4, Rgt(F) = 0.0499, wRref(F2) = 0.1396, T = 293 K.

Cigars have unique aroma and style characteristics. In order to clarify the differences of aroma components between domestic and imported cigars and the material basis of the stylistic characteristics of different cigars, gas chromatography-mass spectrometry (GC-MS) and sensory evaluation were used to compare and analyze the aroma components in the mainstream smoke of four domestic cigars and two imported cigars. The GC-MS results showed that a total of 97 aroma components were measured in the smoke of the six cigars, and the types of aroma components were similar, but there were differences in their contents. In comparison with those of domestic cigars, imported cigars had suitable nicotine content, and higher contents of phytol, neophytadiene, 3-methylpentanoic acid, and (+)-δ-cadinene. To further explore the differences in the aroma components of the six cigars, GC-MS data combined with chemometrics were used to screen out 14 key aroma components based on P-value (P) 1, and Aroma Activity Values (OAV) > 1. The key aroma components of each cigar were obtained, Snow Dream No. 5: cedrol; Wangguan Guocui: 6-methyl-5-hepten-2-one, pyridine, 2-ethyl-6-methylpyrazine; General Achileus No. 3: p-cresol, 2-methylbutyraldehyde, methyl cyclopentenolone; Montecristo No. 4: cedrol, 2-methylbutyraldehyde, guaiacol, 4-vinylguaiacol, methyl cyclopentenolone; Romeo y Julieta Wide Churchills: cedrol, 2,6-dimethylpyrazine, 2-ethyl-6-methylpyrazine, 2-heptanone, phenethyl alcohol; Great Wall No. 2: p-cresol, phenethyl alcohol, geranylacetone, methyl cyclopentenolone, dihydroactinidiolide. The odor descriptors of these compounds were consistent with the aroma profiles that were prominent in the senses of each cigar. This experiment initially explored the differences in aroma composition and style characteristics of cigars and provided data to support the quality improvement of domestic cigars.

Abstract Background Continuation of bevacizumab plus second‐line chemotherapy has significantly improved overall and progression‐free survival in patients with metastatic colorectal cancer (mCRC). However, the cost‐effectiveness of such high cost therapy is still uncertain in China; so this analysis was performed to evaluate the cost‐effectiveness of these treatment options from the Chinese health care system perspective. Methods A cost‐effectiveness analysis was conducted using data from the ML18147 trial (ClinicalTrials.gov identifier NCT00700102) by modeling a partitioned survival model. Main evaluation indicators were quality‐adjusted life years (QALYs) and incremental cost‐effectiveness ratio (ICER) with a willingness to pay (WTP) threshold of $38,201 per QALY. One‐way and probabilistic sensitivity analyses were conducted to assess the robustness and stability of the model. Subgroup and scenario analyses were also performed to make our study more relevant. Results Bevacizumab plus chemotherapy increased 0.12 QALYs and an incremental cost of $22,761.62 compared with chemotherapy, resulting in an ICER of $188,904.09 per QALY. The model was most sensitive to the utility of progression‐free survival and the cost of bevacizumab. Compared with chemotherapy, bevacizumab plus chemotherapy had a 0% cost‐effectiveness probability, and no cost‐effectiveness in subgroups at the WTP threshold of $38,201 per QALY. The scenario analysis found that bevacizumab biosimilar gained an ICER of $126,397.38 per QALY when assuming the cost of drugs was calculated at the most affordable price. Conclusions At the WTP threshold of $38,201 per QALY, continuation of bevacizumab plus chemotherapy is unlikely considered cost‐effective for patients after first progression of mCRC.

Intracutaneous pyonex therapy (IPT), a novel acupuncture technique also known as intradermal thumbtack needle embedding therapy, has been reported to optimize postoperative pain management following perianal surgery. This meta-analysis aimed to analyze the efficacy of IPT for postoperative pain management following perianal surgery. The Cochrane Library, PubMed, EMBASE, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases were systematically searched for randomized controlled trials (RCTs) on IPT as a treatment for postoperative pain management following perianal surgery from inception until June 15, 2022. The analyzed outcomes from the eleven RCTs included in this meta-analysis were as follows: postoperative visual analogue scale(VAS), analgesic duration, ineffective cases following treatment, and adverse events. Subgroup analyses were conducted according to different time points. Risk-of-bias assessment, publication bias analysis, sensitivity analysis, and trial sequential analysis were performed. Of the 895 patients, 450 and 445 were included in the IPT and control groups, respectively. The IPT group showed a better analgesic effect[standard mean difference (SMD) = -0.77, 95% CI: -1.00 to -0.53, P < 0.00001; P for heterogeneity = 0.009, I2 = 59%] and longer analgesic duration [SMD = 0.56, 95% CI: 0.31 to 0.82, P < 0.0001; P for heterogeneity = 0.6, I2 = 0%], fewer ineffective cases following treatment [risk ratio(RR) = 0.23; 95% CI: 0.13 to 0.39, P < 0.00001; P for heterogeneity = 0.76, I2 = 0%], and lower overall occurrence of postoperative complications [RR = 0.35; 95% CI: 0.17 to 0.70; P = 0.003; P for heterogeneity = 0.85, I2 = 0%] than the control group. Thus, our findings indicated that IPT can provide better pain management following perianal surgery compared to controls. This novel approach complements a reasonable modality for postoperative multimodal analgesia and is worth promoting.

This study addresses the issue of a significant amount of unmelted powder adhering to the surface of Laser Powder Bed Fusion (LPBF) porous titanium alloy scaffolds, and the current inability of existing technologies to effectively handle such surface defects. Porous titanium alloy scaffolds with a triple periodical minimal surface (TPMS) Gyroid structure were prepared using powder bed fusion technology for dynamic chemical polishing. The spatial and surface morphology, as well as the mechanical properties of the scaffolds, were evaluated before and after treatment. Concurrently, fluid finite element simulation was employed to analyze the flow state of the solution inside the porous scaffold during dynamic chemical polishing. Cell culture samples were prepared and subjected to dynamic chemical polishing to study the specific effects of scaffold surface morphology on cell activity. The results indicate that the surface treatment effect, internal and external homogeneity, and dynamic and static mechanical properties of the porous scaffolds with a Gyroid structure are significantly improved after dynamic chemical polishing. Additionally, it was found that dynamic chemical polishing could effectively reduce the micrometer roughness and increase the nanometer roughness of the sample surface, thereby enhancing the adhesion, proliferation, and differentiation activities of Human Bone Mesenchymal Stem cells.

Abstract Background Peritoneal dialysis (PD) remains limited due to dialysis failure caused by peritoneal fibrosis. Tamoxifen (TAM), an inhibitor of estrogen receptor 1 (ESR1), has been reported to treat fibrosis, but the underlying mechanism remains unknown. In this study, we sought to explore whether tamoxifen played an anti-fibrotic role by affecting transcription factor ESR1. Methods ESR1 expression was detected in the human peritoneum. Mice were daily intraperitoneally injected with 4.25% glucose PD dialysate containing 40 mM methylglyoxal for 2 weeks to establish PD-induced peritoneal fibrosis. Tamoxifen was administrated by daily gavage, at the dose of 10 mg/kg. Chromatin immunoprecipitation (ChIP) and dual‐luciferase reporter assay were performed to validate ESR1 bound H19 promoter. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of H19 on the mesothelial-mesenchymal transition (MMT) of human peritoneal mesothelial cells (HPMCs). Intraperitoneal injection of nanomaterial-wrapped 2′-O-Me-modified small interfering RNA was applied to suppress H19 in the mouse peritoneum. RNA immunoprecipitation and RNA pull-down assays demonstrated binding between H19 and p300. Exfoliated peritoneal cells were obtained from peritoneal dialysis effluent to analyze the correlations between ESR1 (or H19) and peritoneal solute transfer rate (PSTR). Results ESR1 was increased significantly in the peritoneum after long-term exposure to PD dialysate. Tamoxifen treatment ameliorated high glucose-induced MMT of HPMCs, improved ultrafiltration rate, and decreased PSTR of mouse peritoneum. Tamoxifen reduced the H19 level by decreasing the ESR1 transcription of H19. Depletion of H19 reversed the pro-fibrotic effect of high glucose while ectopic expression of H19 exacerbated fibrotic pathological changes. Intraperitoneal injection of nanomaterial-wrapped 2′-O-Me-modified siRNAs targeting H19 mitigated PD-related fibrosis in mice. RNA immunoprecipitation (RIP) and RNA pull-down results delineated that H19 activated VEGFA expression by binding p300 to the VEGFA promoter and inducing histone acetylation of the VEGFA promoter. ESR1 and H19 were promising targets to predict peritoneal function. Conclusions High glucose-induced MMT of peritoneal mesothelial cells in peritoneal dialysis via activating ESR1. In peritoneal mesothelial cells, ESR1 transcribed the H19 and H19 binds to transcription cofactor p300 to activate the VEGFA. Targeting ESR1/H19/VEGFA pathway provided new hope for patients undergoing peritoneal dialysis. Graphic Abstract

A new class of bio-composites was developed by utilizing four kinds of lignocellulosic biomass fiber (bagasse, bamboo, rice husk, and rice straw) as filling fibers. Poly-β-hydroxybutyrate (PHB) and poly(butylene succinate) (PBS) in a mixture ratio of 7:3 were used as matrix materials with hot-press molding. The performance of the resulting composites was evaluated by compositional analyses, mechanical analysis, Fourier transform infrared (FTIR) spectroscopy, thermogravimetry, and morphological analysis. The interfacial adhesion, thermal stability, and comprehensive mechanical properties of the alkali treated bamboo/PHB/PBS composite were highest among the four bio-composites. The bending strength, tensile strength, and impact strength for alkali treated bamboo/PHB/PBS composite was 19.82 MPa, 12.97 MPa, and 4.30 kJ/m2, respectively. The thermal stability for NaOH modified bamboo/PHB/PBS composite was slightly superior to the other three composites, with the initial pyrolysis temperature of 248 °C, moderate pyrolysis speed, and the amount of pyrolysis residue (5.81%). The results showed the suitability of biomass fiber and biodegradable polymer for producing environmentally friendly composite materials.

Abstract Improper layout of drainage structures and inadequate insulation measures in cold tunnels can result in varying degrees of frost formation during operation. This study focuses on the Hongtoushan highway tunnel as an example, where the distribution characteristics of the temperature field around the lower drainage structure under different arrangements are investigated through indoor model testing. The results indicate that there is a significant hysteresis phenomenon in temperature changes across the cross-section as the burial depth increases. With an increase in the burial depth of the surrounding rock, the hysteresis time of temperature changes gradually elongates. The temperature variation pattern can be approximated by a cubic polynomial. In the vertical section, as the tunnel depth increases, the temperature of the surrounding rock in the lower part of the tunnel gradually rises while the amplitude of temperature change diminishes. The temperature near the centerline is relatively lower compared to the sides, where the temperature gradually increases moving away from the centerline.

Alkali-treated bagasse fiber was used as a process variable for optimization of the properties of polybutylene succinate/poly(lactic acid)-based biocomposites using Box-Behnken design (BBD) and response surface methodology (RSM). The optimum conditions for three factors, i.e., NaOH-treated bagasse fiber (0.55 to 1.65 g), polybutylene succinate (1.1 to 2.3 g), and poly(lactic acid) (2.2 to 3.4 g) on the bending strength of biocomposite were investigated. The optimum combination was 0.91 g of NaOH-treated bagasse fiber, 1.14 g of polybutylene succinate, and 3.10 g of poly(lactic acid). The bending strength for NaOH-treated bagasse fiber/polybutylene succinate/ poly(lactic acid) composite was 27.0 MPa, which was 26.0% higher than native bagasse fiber-based composite. The composites were also characterized by thermogravimetric analysis, mechanical testing, Fourier transform infrared, scanning electron microscopy, water absorption, and contact angle tests. Results demonstrated that the bending strength, impact strength, and tensile strength of alkali treated bagasse fiber-based biocomposite increased by 26.0%, 15.5%, and 23.3%, separately, compared with native bagasse-based composite after sequential homogenization, compounding, and hot pressing. The hydrophobicity for alkali-treated bagasse fiber/PBS/PLA was also improved. Thus, NaOH-treated biomass materials/biodegradable polymer was judged to be suitable for preparing green composite materials.

Skin is the largest organ in the human body and requires proper dressing to facilitate healing after an injury. Wounds on movable parts, such as the elbow, knee, wrist, and neck, usually undergo delayed and inefficient healing due to frequent movements. To better accommodate movable wounds, a variety of functional hydrogels have been successfully developed and used as flexible wound dressings. On the one hand, the mechanical properties, such as adhesion, stretchability, and self-healing, make these hydrogels suitable for mobile wounds and promote the healing process; on the other hand, the bioactivities, such as antibacterial and antioxidant performance, could further accelerate the wound healing process. In this review, we focus on the recent advances in hydrogel-based movable wound dressings and propose the challenges and perspectives of such dressings.

Abstract Background Tyrosine kinase inhibitors combined with conventional chemotherapy (CC) in treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) has achieved promising efficacy and safety outcomes. The study was conducted to compare the cost-effectiveness between imatinib (HANSOH Pharma, Jiangsu, China) and dasatinib (CHIATAI TIANQING Pharma, Jiangsu, China) in treating pediatric Ph-positive ALL when combined with CC from the perspective of the health system in China. Methods A Markov model was established to simulate a hypothetical cohort of pediatric Ph-positive ALL patients receiving imatinib or dasatinib, combined with CC. The model was designed using a 10-year horizon, a 3- month cycle, and a 5% discount rate. Three health states were included: alive with progression-free survival, progressed disease, and death. Patient characteristics and transition probabilities were estimated based on clinical trials. Other relevant data, such as direct treatment costs and health utility data were extracted from published literature and Sichuan Province’s centralized procurement and supervision platform. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the results. The willingness-to-pay (WTP) was set as three times China’s GDP per capita in 2021. Results In the base-case analysis, the total medical costs were $89,701 and $101,182, and the quality-adjusted life years (QALYs) gained were 1.99 and 2.70, for imatinib and dasatinib regimens, respectively. The incremental cost-effectiveness ratio for dasatinib versus imatinib was $16,170/QALY. The probabilistic sensitivity analysis indicated that treatment with dasatinib combined with CC achieved a 96.4% probability of cost-effectiveness at a WTP threshold of $37,765/QALY. Conclusions Dasatinib combined with CC is likely to be a cost-effective strategy compared to imatinib combination therapy for pediatric Ph-positive ALL in China at a WTP threshold of $37,765/QALY.

Abstract Immune checkpoint blockade (ICB) treatment of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection may activate viral-specific T cells to attack HBV infected hepatocytes and thus induce immune-related liver injury. Therefore, it is important to deeply understand the impacts of HBV infection on HCC immune microenvironment in order to better design effective immunotherapies for HBV+ (HBV infected) HCC patients. Here, We performed cytometry by time-of-flight (CyTOF) analyses to characterize the distinct immune compositions of HCC tumors, tumor borders, and their associations with HCC/HBV related clinical characteristics. We identified 31 distinct immune clusters and found significant associations between immune signatures with clinicopathological features of HCC. We further revealed the HBV infection had more effects on shaping immune compositions in tumor borders than in tumors, with the significant enrichment of HBV-specific PD-1+CD8+ tissue-resident memory T (TRM) cells in tumor borders of HBV+ patients. We confirmed this subset with a more exhausted phenotype and respond more actively under anti-PD-L1 treatment, suggesting its involvement in immune-related liver injury induced by ICB treatment to HBV+ HCC patients. Our study shows it may be necessary to consider antiviral prophylaxis for HBV+ HCC patients receiving ICB treatment.

The objective of this paper is to design a fast and efficient immune algorithm for solving various optimization problems. The immune algorithm (IA), which simulates the principle of the biological immune system, is one of the nature-inspired algorithms and its many advantages have been revealed. Although IA has shown its superiority over the traditional algorithms in many fields, it still suffers from the drawbacks of slow convergence and local minima trapping problems due to its inherent stochastic search property. Many efforts have been done to improve the search performance of immune algorithms, such as adaptive parameter setting and population diversity maintenance. In this paper, an improved immune algorithm (IIA) which utilizes a parallel mutation mechanism (PM) is proposed to solve the Lennard-Jones potential problem (LJPP). In IIA, three distinct mutation operators involving cauchy mutation (CM), gaussian mutation (GM) and lateral mutation (LM) are conditionally selected to be implemented. It is expected that IIA can effectively balance the exploration and exploitation of the search and thus speed up the convergence. To illustrate its validity, IIA is tested on a two-dimension function and some benchmark functions. Then IIA is applied to solve the LJPP to exhibit its applicability to the real-world problems. Experimental results demonstrate the effectiveness of IIA in terms of the convergence speed and the solution quality.

Abstract WDR5 is a highly conserved protein that performs multiple scaffolding functions in the context of chromatin. However, efforts to understand the function of WDR5 in normal tissues physiologically are quite limited so far. In our study, we explored the function of Wdr5 in erythropoiesis and hematopoiesis by using a hematopoietic-specific Wdr5 knockout mouse model. We found that loss of Wdr5 mediated by Vav-iCre leads to embryonic lethality with defective erythropoiesis. In addition, Wdr5-deficiency completely impairs the hematopoietic stem and progenitor cells function and might alter the immunophenotype of these stem cells and progenitors by decreasing c-Kit expression. Collectively, we identified the pivotal role of Wdr5 in fetal hematopoiesis and erythropoiesis as the de novo findings.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by abnormal cell proliferation, apoptosis repression and myeloid differentiation blockade of hematopoietic stem/progenitor cells. Developing and identifying novel therapeutic agents to reverse the pathological processes of AML are of great significance. Here in this study, we found that a fungus-derived histone deacetylase inhibitor, Apicidin, presents promising therapeutic effect on AML by inhibiting cell proliferation, facilitating apoptosis and inducing myeloid differentiation of AML cells. Mechanistic investigation revealed that QPCT is identified as a potential downstream target of Apicidin, which exhibits significantly decreased expression in AML samples compared with the normal controls and is remarkably up-regulated in AML cells upon Apicidin management. Functional study and rescue assay demonstrated that QPCT depletion further promotes cell proliferation, inhibits apoptosis and impairs myeloid differentiation of AML cells, alleviating the anti-leukemic effect of Apicidin on AML. Our findings not only provide novel therapeutic target for AML, but also lay theoretical and experimental foundation for the clinical application of Apicidin in AML patients.

Summary: To investigate whole-slide-level prediction in the field of artificial intelligence identification of dMMR/pMMR from hematoxylin and eosin (H&E) in colorectal cancer (CRC), we established a segmentation-based dMMR/pMMR deep learning detector (SPEED). Our model was approximately 1,700 times faster than that of the classification-based model. For the internal validation cohort, our model yielded an overall AUC of 0.989. For the external validation cohort, the model exhibited a high performance, with an AUC of 0.865. The human‒machine strategy further improved the model performance for external validation by an AUC up to 0.988. Our whole-slide-level prediction model provided an approach for dMMR/pMMR detection from H&E whole slide images with excellent predictive performance and less computer processing time in patients with CRC.

Introduction Intraperitoneal dexamethasone has been reported to be effective to reduce the incidence of postoperative nausea and vomiting (PONV). Therefore, this meta-analysis will analyse the efficacy and safety of intraperitoneal dexamethasone on PONV following laparoscopy.Methods and analysis Electronic databases (eg, Cochrane Library, PubMed, Excerpta Medica Database, Web of Science, National Institute of Informatics, Oriental Medicine Advanced Searching Integrated System and China National Knowledge Infrastructure) and clinical trial registries will be systematically searched from their inception to 1 October 2022. After the study and data collection processes, we will identify randomised controlled trials that reported details of intraperitoneal dexamethasone on PONV following laparoscopy to conduct a meta-analysis. We will perform the study process and data collection separately. The collected data will be statistically analysed using Review Manager 5.4 software. The risk of bias will be assessed using the Cochrane risk-of-bias tool 2. The Grading of Recommendations Assessment, Development and Evaluation certainty assessment, and a trial sequential analysis will be conducted to ensure the accuracy of this meta-analysis.Ethics and dissemination Ethical approval and patient consent are not required since this study is a systematic review and meta-analysis. The findings of this meta-analysis will be submitted to a peer-reviewed journal for publication.PROSPERO registration number CRD42022362924.

Abstract Despite the development of advanced technologies for interventional coronary reperfusion after myocardial infarction, a substantial number of patients experience high mortality due to myocardial ischemia‐reperfusion (MI/R) injury. An in‐depth understanding of the mechanisms underlying MI/R injury can provide crucial strategies for mitigating myocardial damage and improving patient survival. Here, it is discovered that the 4‐hydroxy‐2‐nonenal (4‐HNE) accumulates during MI/R, accompanied by high rates of myocardial ferroptosis. The loss‐of‐function of aldehyde dehydrogenase 2 (ALDH2), which dissipates 4‐HNE, aggravates myocardial ferroptosis, whereas the activation of ALDH2 mitigates ferroptosis. Mechanistically, 4‐HNE targets glutathione peroxidase 4 (GPX4) for K48‐linked polyubiquitin‐related degradation, which 4‐HNE‐GPX4 axis commits to myocyte ferroptosis and forms a positive feedback circuit. 4‐HNE blocks the interaction between GPX4 and ovarian tumor (OTU) deubiquitinase 5 (OTUD5) by directly carbonylating their cysteine residues at C93 of GPX4 and C247 of OTUD5, identifying OTUD5 as the novel deubiquitinase for GPX4. Consequently, the elevation of OTUD5 deubiquitinates and stabilizes GPX4 to reverse 4‐HNE‐induced ferroptosis and alleviate MI/R injury. The data unravel the mechanism of 4‐HNE in GPX4‐dependent ferroptosis and identify OTUD5 as a novel therapeutic target for the treatment of MI/R injury.

Eucalyptus grandis × Eucalyptus urophylla ‘GLGU9’ is one of the most commonly planted tree species in South China. It is a new variety created by Guangxi Zhuang Autonomous Region Forestry Research Institute. As a fast-growing species, the poor dimensional stability is one of its main drawbacks, which restricts its applications. Thermal treatment is one of the effective methods to improve the dimensional stability of wood. GLGU9 wood was treated using thermal modification with palm oil. The oil was used as a heating medium and a shielding material at temperatures of 150, 170, 190, 200, and 210 °C, at various treatment durations of 1.5, 3, 4.5 and 6 h. To investigate the effect of palm oil thermal treatment on dimensional stability, the anti-shrink efficiency (ASE1) and anti-swelling efficiency (ASE2) were examined. The results indicated that the ASE1 and ASE2 were increased by 62.8% and 56.6% at 210 °C for 6 h treatment, respectively.

Abstract Background Prior studies have reported conflicting results on the effect of sugammadex on postoperative pulmonary complications (PPCs) and research on this topic in transapical-transcatheter aortic valve implantation (TA-TAVI) was sparse. The current study aimed to investigate whether there were differences in the incidence of PPCs between two muscle relaxant strategies (rocuronium/sugammadex vs. cisatracurium/neostigmine) in patients undergoing TA-TAVI. Methods This retrospective observational study enrolled 245 adult patients underwent TA-TAVI between October 2018 and January 2021. The patients were grouped according to the type of muscle relaxant strategies (115 with rocuronium/sugammadex in the R/S group and 130 with cisatracurium/neostigmine in the C/N group, respectively). Pre- and intraoperative variables were managed by propensity score match (PSM) at a 1:2 ratio. PPCs (i.e., respiratory infection, pleural effusion, pneumothorax, atelectasis, respiratory failure, bronchospasm and aspiration pneumonitis) were evaluated from the radiological and laboratory findings. Results After PSM, 91 patients in the R/S group were selected and matched to 112 patients in the C/N group. Patients in the R/S group showed lower PPCs rate (45.1% vs. 61.6%, p = 0.019) compared to the C/N group. In addition, the R/S group showed significant shorter extubation time (7.2 ± 6.2 vs. 10.3 ± 8.2 min, p = 0.003) and length of hospital stay (6.9 ± 3.3 vs. 8.0 ± 4.0 days, p = 0.034). Conclusion The rocuronium/sugammadex muscle relaxant strategy decreases the incidence of PPCs in patients undergoing TA-TAVI when compared to cisatracurium/neostigmine strategy. Trial registration ChiCTR, ChiCTR2100044269. Registered March 14, 2021-Prospectively registered, http://www.Chictr.org.cn .

Tandem gene duplication is an important process in plant adaptive evolution, but the generation mechanism and expression characteristics of tandem duplicated (TD) genes and their roles in plant stress response have not been rigorously investigated. Here, we take grapevine (V. vinifera) as an example to show that recent large-scale tandem gene duplication, mediated by long terminal repeat retrotransposons, promotes the expansion of specific gene families involved in response to biotic stress, biosynthesis of various secondary metabolites and adaptive evolution. More importantly, compared with interspersed duplicated genes, TD genes exhibit a position and synergistic effect, and multifaceted overactivity and play key roles in response to biotic stress caused by pathogens such as P. viticola (downy mildew) and Erysiphe necator (powdery mildew). The higher co-expression level of TD genes is not only reflected in the co-response to biotic stress, but also universal in various tissues and developmental stages. This may be related to a higher level of co-regulation and a higher transcription factor regulatory efficiency, as well as sequence similarity within gene clusters. Moreover, most TD genes are expressed asymmetrically, while maintaining a relative balance, which may be beneficial for the retention and functional differentiation of the TD genes. These findings not only advance our understanding of the evolution of the V. vinifera genome and the evolution dynamics of the TD genes which has often been overlooked, but also provide guidance for the directional selection in breeding work.

Abstract Interleukin-2 (IL-2) is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells (Tregs) and effector cells, leading to paradoxical consequences. Here, we report a strategy that exploited genetic code expansion-guided incorporation of the latent bioreactive artificial amino acid fluorosulfate-L-tyrosine (FSY) into IL-2 for proximity-enabled covalent binding to IL-2Rα to selectively promote Treg activation. We found that FSY-bearing IL-2 variants, such as L72-FSY, covalently bound to IL-2Rα via sulfur-fluoride exchange when in proximity, resulting in persistent recycling of IL-2 and selectively promoting the expansion of Tregs but not effector cells. Further assessment of L72-FSY-expanded Tregs demonstrated that L72-FSY maintained Tregs in a central memory phenotype without driving terminal differentiation, as demonstrated by simultaneously attenuated expression of lymphocyte activation gene-3 (LAG-3) and enhanced expression of programmed cell death protein-1 (PD-1). Subcutaneous administration of L72-FSY in murine models of pristane-induced lupus and graft-versus-host disease (GvHD) resulted in enhanced and sustained therapeutic efficacy compared with wild-type IL-2 treatment. The efficacy of L72-FSY was further improved by N-terminal PEGylation, which increased its circulatory retention for preferential and sustained effects. This proximity-enabled covalent binding strategy may accelerate the development of pleiotropic cytokines as a new class of immunomodulatory therapies.

Objective: To explore the structural characteristics of condensed tannins from Ziziphus jujuba leaves and their effect on tyrosinase and the inhibition mechanism for melanogenesis. Methods: The condensed tannins from Z. jujuba leaves were isolated and purified on the basis of Sephadex LH-20 gel column chromatography, and their structural features were identified by thiolysis coupled with high-performance liquid chromatography-electrospray ionization mass spectrometry (Thiolysis-HPLC-ESI-MS). Besides, the inhibitory mechanism of Z. jujuba leaves condensed tannins on tyrosinase was also systematically investigated by enzyme kinetics, UV-vis absorption and fluorescence spectroscopy. Finally, CCK-8 assay, L-DOPA oxidation assay, NaOH cleavage assay and real-time fluorescence quantitative PCR were employed to probe into the effects of Z. jujuba leaves condensed tannins on the proliferation, tyrosinase activity, melanogenesis and the level of melanogenesis-related gene expression of mouse melanoma cells (B16F10). Results: The condensed tannins from Z. jujuba leaves were mainly composed of (epi)catechin and (epi)gallocatechin. Z. jujuba leaves condensed tannins were found to strongly inhibit on both monophenolase and diphenolase of tyrosinase, and the inhibition against diphenolase was proved to be reversible and mixed-type. It was also observed that the condensed tannins from Z. jujuba leaves could effectively inhibit the cell viability, tyrosinase activity, melanin content, as well as the mRNA expression of TYR, TRP-1 and MITF genes in B16F10 cells. Conclusion: Based on the comprehensive analysis of the biological effects of condensed tannins from Z. jujuba leaves at enzyme level and cell level, we could clarify the molecular inhibition mechanism of Z. jujuba leaves condensed tannins on melanogenesis in B16F10 cells. This study would provide a theoretical basis for the later development of Z. jujuba leaves condensed tannins as new whitening cosmetic additives and preservatives for fruits and vegetables.