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Abstract The BESIII experiment has been operating since 2009 and has received several upgrades, to study the $$\tau $$ τ -charm physics utilizing the BEPCII accelerator. The BEPCII is a double-ring multi-bunch collider with a luminosity of $$1 \times 10^{33} \, {\text {cm}}^{-2} \, {\text {s}}^{-1}$$ 1 × 10 33 cm - 2 s - 1 optimized at a center-of-mass (cms) energy of $$2 \times 1.89$$ 2 × 1.89 GeV. The rich physics topics, long lifetime and the large volume of data present challenges to offline data processing. This paper describes the design and implementation of the offline software system to meet the requirements and challenges of BESIII, including offline software architecture, geometry management, database management, event data model and tag-based analysis.

Abstract Altered cholesterol metabolism has been linked to a poor prognosis in various types of cancer. Cholesterol oxidation can lead to lipid peroxidation, membrane damage, and cell death. Ferroptosis is a regulated form of cell death characterized by the accumulation of lipid peroxides, which significantly inhibits the growth of ovarian cancer cells. SQLE is the primary enzyme responsible for catalyzing cholesterol lipid synthesis and is notably expressed in ovarian cancer tissues and cells. This study aims to investigate the role of squalene monooxygenase (SQLE) in ferroptosis in ovarian cancer. The protein and mRNA expression of SQLE was assessed using qRT-PCR, Western Blot, and immunohistochemistry. The association between SQLE and ferroptosis was demonstrated through analysis of TCGA and GTEx databases, TMT protein sequencing, as well as validation by qRT-PCR, Western Blot, immunofluorescence, ROS detection, and lipid peroxide detection. Animal experiments further confirmed the relationship between SQLE and ferroptosis in ovarian cancer. The protein and mRNA expression of SQLE was found to be upregulated in both ovarian cancer tissues and cell lines. Decreased SQLE expression led to ferroptosis in ovarian cancer cells, thereby increasing their sensitivity to ferroptosis inducers. Our research demonstrates that SQLE is significantly upregulated in both ovarian cancer tissues and cells. The overexpression of SQLE in ovarian cancer may facilitate tumorigenesis by conferring resistance to ferroptosis, thus shedding light on potential novel therapeutic strategies for ovarian cancer.

Abstract Understanding the neuropathogenesis of impaired social cognition in autism spectrum disorders (ASD) is challenging. Altered cortical parvalbumin-positive (PV+) interneurons have been consistently observed in ASD, but their roles and the underlying mechanisms remain poorly understood. In our study, we observed a downward-shifted spectrum of PV expression in the developing medial prefrontal cortex (mPFC) of ASD mouse models due to decreased activity of PV+ neurons. Surprisingly, chemogenetically suppressing PV+ neuron activity during postnatal development failed to induce ASD-like behaviors. In contrast, lowering excitatory activity in the developing mPFC not only dampened the activity state and PV expression of individual PV+ neurons, but also replicated ASD-like social deficits. Furthermore, enhancing excitation, but not PV+ interneuron-mediated inhibition, rescued social deficits in ASD mouse models. Collectively, our findings propose that reduced excitatory activity in the developing mPFC may serve as a shared local circuitry mechanism triggering alterations in PV+ interneurons and mediating impaired social functions in ASD.

Abstract Previous studies have shown that the three-dimensional (3D) geometric and electronic structure of molecules play a crucial role in determining their key properties and intermolecular interactions. Therefore, it is necessary to establish a quantum chemical (QC) property database containing the most stable 3D geometric conformations and electronic structures of molecules. In this study, a high-quality QC property database, called QuanDB, was developed, which included structurally diverse molecular entities and featured a user-friendly interface. Currently, QuanDB contains 154,610 compounds sourced from public databases and scientific literature, with 10,125 scaffolds. The elemental composition comprises nine elements: H, C, O, N, P, S, F, Cl, and Br. For each molecule, QuanDB provides 53 global and 5 local QC properties and the most stable 3D conformation. These properties are divided into three categories: geometric structure, electronic structure, and thermodynamics. Geometric structure optimization and single point energy calculation at the theoretical level of B3LYP-D3(BJ)/6-311G(d)/SMD/water and B3LYP-D3(BJ)/def2-TZVP/SMD/water, respectively, were applied to ensure highly accurate calculations of QC properties, with the computational cost exceeding 107 core-hours. QuanDB provides high-value geometric and electronic structure information for use in molecular representation models, which are critical for machine-learning-based molecular design, thereby contributing to a comprehensive description of the chemical compound space. As a new high-quality dataset for QC properties, QuanDB is expected to become a benchmark tool for the training and optimization of machine learning models, thus further advancing the development of novel drugs and materials. QuanDB is freely available, without registration, at https://quandb.cmdrg.com/ .

Abstract Background The clinical manifestations of COVID-19 range from asymptomatic, mild to moderate, severe, and critical disease. Host genetic variants were recognized to affect the disease severity. However, the genetic landscape differs among various populations. Therefore, we explored the variants associated with COVID-19 severity in the Guangdong population. Methods A total of 314 subjects were selected, of which the severe and critical COVID-19 patients were defined as “cases”, and the mild and moderate patients were defined as “control”. Twenty-two variants in interferon-related genes and FOXP4 were genotyped using the MassARRAY technology platform. Results IFN signaling gene MX1 rs17000900 CA + AA genotype was correlated with a reduced risk of severe COVID-19 in males (P = 0.001, OR = 0.050, 95%CI = 0.008–0.316). The AT haplotype comprised of MX1 rs17000900 and rs2071430 was more likely to protect against COVID-19 severity (P = 6.3E-03). FOXP4 rs1886814 CC genotype (P = 0.001, OR = 3.747, 95%CI = 1.746–8.043) and rs2894439 GA + AA genotype (P = 0.001, OR = 5.703, 95% CI = 2.045–15.903) were correlated with increased risk of severe COVID-19. Haplotype CA comprised of rs1886814 and rs2894439 was found to be correlated with adverse outcomes (P = 7.0E-04). FOXP4 rs1886814 CC (P = 0.0004) and rs2894439 GA + AA carriers had higher neutralizing antibody titers (P = 0.0018). The CA + AA genotype of MX1 rs17000900 tended to be correlated with lower neutralizing antibody titers than CC genotype (P = 0.0663), but the difference was not statistically significant. Conclusion Our study found a possible association between MX1 and FOXP4 polymorphisms and the severity of COVID-19. Distinguishing high-risk patients who develop severe COVID-19 will provide clues for early intervention and individual treatment strategies.

Avian influenza viruses (AIVs) are the origin of multiple mammal influenza viruses. The genetic determinants of AIVs adapted to humans have been widely elucidated, however, the molecular mechanism of cross-species transmission and adaptation of AIVs to canines are still poorly understood. In this study, two H3N2 influenza viruses isolated from a live poultry market (A/environment/Guangxi/13431/2018, GX13431) and a swab sample from a canine (A/canine/Guangdong/0601/2019, GD0601) were used to investigate the possible molecular basis that determined H3N2 AIV adapting to canine. We found that GD0601 exhibited more robust polymerase activity in cells and higher pathogenicity in mice compared with its evolution ancestor H3N2 AIV GX13431. A series of reassortments of the ribonucleoprotein (RNP) complex showed that the PB2 subunit was the crucial factor that conferred high polymerase activity of GD0601, and the substitution of I714S in the PB2 subunit of GD0601 attenuated the replication and pathogenicity in mammal cells and the mouse model. Mechanistically, the reverse mutation of I714S in the PB2 polymerase subunit which was identified in AIV GX13431 reduced the nuclear import efficiency of PB2 protein and interfered with the interactions of PB2-PA/NP that affected the assembly of the viral RNP complex. Our study reveals amino acid mutation at the position of 714 in the nuclear localization signal (NLS) area in PB2 plays an important role in overcoming the barrier from poultry to mammals of the H3N2 canine influenza virus and provides clues for further study of mammalian adaptation mechanism of AIVs.

Molecular conformations generation (MCG) aims to efficiently obtain reasonable and stable three-dimensional (3D) atomic coordinates of the atoms in the molecule from scratch, providing a structural foundation for molecular representation learning models and advanced downstream molecular design tasks such as molecular property prediction, molecular generation, and molecular docking. Existing MCG methods mostly rely on indirect distance-based strategies, which which can result in geometrically unrealistic conformations, or direct coordinate-based methods, which have larger search spaces and are prone to overfitting. Therefore, this study introduces Conf-GEM, a novel geometric information-assisted direct conformation generation model based on E-GeoGNN, a geometrically augmented 3D graph neural network with multiple scales. Pre-training and divide-and-conquer strategies, are integrated into the proposed model. Conf-GEM outperforms RDKit and nine deep-learning-based MCG models on the GEOM-QM9 and GEOM-Drugs datasets, achieving conformational coverage of 96.69% and 96.07%, respectively, without force field optimization. It also excels on the X-ray diffraction crystal structure dataset with up to 97.04% conformational coverage. In conclusion, Conf-GEM provides a novel solution for stabilizing 3D conformations generation. We provide an online prediction service (https://confgem.cmdrg.com) with a user-friendly interface for researchers.

Smart dressings integrated with bioelectronics have attracted considerable attention and become promising solutions for skin wound management. However, due to the mechanical distinction between human body and the interface of electronics, previous smart dressings often suffered obvious degradation in electrical performance when attached to the soft and curvilinear wound sites. Here, we report a stretchable dressing integrated with temperature and pH sensor for wound status monitoring, as well as an electrically controlled drug delivery system for infection treatment. The wound dressing was featured with the deployment of liquid metal for seamless connection between rigid electrical components and gold particle-based electrodes, achieving a stretchable soft-hard interface. Stretching tests showed that both the sensing system and drug delivery system exhibited good stretchability and long-term stable conductivity with the resistance change rate less than 6 % under 50 % strain. Animal experiments demonstrated that the smart dressing was capable of detecting bacterial infection via the biomarkers of temperature and pH value and the infection factors of wound were significantly improved with therapy through electrically controlled antibiotics releasing. This proof-of-concept prototype has potential to significantly improve management of the wound, especially those with dynamic strain.

Background: Splenic sclerosing angiomatoid nodular transformation (SANT) is a rare benign nodular lesion in the red medulla of the spleen. In the past, SANT has not been consistently recognized as the name for this condition and was often misdiagnosed for other conditions. In recent years, SANT has been acknowledged by most scholars as multiple reports have been published. Aim: To assess the clinicopathological features of SANT to identify the histological characteristics of SANT to improve diagnosis and clinical treatment. Materials and Methods: We assessed 25 cases of SANT diagnosed at Zhongshan Hospital affiliated with Fudan University from September 2014 to October 2021, including 14 men and 11 women, aged 24–62 years old. Results: Fourteen cases were complicated with benign tumors of the liver, pancreas, kidney, uterus, and prostate. One case was complicated with renal clear cell carcinoma, and one was complicated with hepatocellular carcinoma. The gross neoplasm is multinodular and well defined. Histologically, angiomatoid nodules are composed of fattened, round, or irregular blood vessels, with or without red blood cells in the lumen, with unequal red blood cell extravasation, and fibrocytes around the nodules. The hemangiomatous nodules were positive for CD31 and CD34, while the vascular wall smooth muscle cells and fibrocytes around the nodules were positive for SMA. Conclusion: The diagnosis of SANT requires a combination of immunohistochemical and histological features, and early splenectomy is crucial for treatment.

Interferon-induced transmembrane proteins (IFITMs) are upregulated by interferons. They are not only highly conserved in evolution but also structurally consistent and have almost identical structural domains and functional domains. They are all transmembrane proteins and have multiple heritable variations in genes. The IFITM protein family is closely related to a variety of biological functions, including antiviral immunity, tumor formation, bone metabolism, cell adhesion, differentiation, and intracellular signal transduction. The progress of the research on its structure and related functions, as represented by IFITM3, is reviewed.

The annual co-circulation of two influenza A subtypes, H1N1 and H3N2, viruses in humans poses significant public health threats worldwide. However, the continuous antigenic drift and shift of influenza viruses limited the effectiveness of current seasonal influenza vaccines, necessitating the development of new vaccines against both seasonal and pandemic viruses. One potential solution to this challenge is to improve inactivated vaccines by including multiple T-cell epitopes. In this study, we designed stabilized trimeric recombinant mosaic HA proteins named HAm, which contain the most potential HA T-cell epitopes of seasonal influenza A virus. We further evaluated the antigenicity, hemagglutinin activity, and structural integrity of HAm and compared its immunogenicity and efficacy to a commercial quadrivalent inactivated influenza vaccine (QIV) in mice. Our results demonstrated that the HAm vaccine was able to induce broadly cross-reactive antibodies and T-cell responses against homologous, heterologous, and heterosubtypic influenza-naive mice. Additionally, the HAm antigens outperformed QIV vaccine antigens by eliciting protective antibodies against panels of antigenically drifted influenza vaccine strains from 2009 to 2024 and protecting against ancestral viruses’ lethal challenge. These results suggest that the HAm vaccine is a promising potential candidate for future universal seasonal and pandemic influenza vaccine development.

Many traditional villages have been degraded to a certain extent due to urbanization and out-of-control management. In addition, due to the lack of recognition and continuation of spatial texture in some village conservation and planning that, in turn, resulting in the gradual disappearance of their distinctive landscape feature. Studying the spatial form of traditional villages helps preserve the authenticity of traditional villages as cultural landscape and inherits traditional historical characteristics. Using Puping Village in Zhangzhou City, Fujian Province as an example, this paper obtains the integrated information data of the village through UAV oblique photography, classifies and extracts the spatial constitution of the traditional village using digital technology, quantitatively analyses it from macroscopic to microscopic, and summarizes the spatial morphology analysis method of the traditional village. The results demonstrate that digital technology can effectively and accurately complete data collection and can provide an objective basis for zoning conservation of traditional villages based on the distinction between new and historic buildings. In addition, digital information collection on the traditional villages landscape features will prepare for the establishment of a database and comparative analysis in the future. We further suggest that digital technology analysis needs to be combined with traditional methods to have a deeper understanding of the formation process of village spatial morphology. The results of the practice in Puping Village show that the use of digital technology can provide a scientific basis for the protection and planning of traditional villages, and that this method is adaptable, which can help to efficiently collect and analyze data on landscape characteristics of other similar villages in China, and support innovative methodologies and technologies for China’s rural revitalization efforts.

Carbon dots (CDs) have garnered extensive interest in basic physical chemistry as well as in biomedical applications due to their low cost, good biocompatibility, and great aqueous solubility. However, the synthesis of multi-functional carbon dots has always been a challenge for researchers. Here, we synthesized novel CDs with a high quantum yield of 28.2% through the straightforward hydrothermal method using Diaminomaleonitrile and Boc-D-2, 3-diaminopropionic acid. The size, chemical functional group, and photophysical properties of the CDs were characterized by TEM, FTIR, XPS, UV, and fluorescence. It was demonstrated in this study that the prepared CDs have a high quantum yield, excellent photostability, and low cytotoxicity. Regarding the highly water-soluble property of CDs, they were proven to possess selective and sensitive behavior against Cu2+ ions (linear range = 0–9 μM and limit of detection = 1.34 μM). Moreover, the CDs were utilized in fluorescent ink in anti-counterfeiting measures. Because of their low cytotoxicity and good biocompatibility, the CDs were also successfully utilized in cell imaging. Therefore, the as-prepared CDs have great potential in fluorescence sensing, anti-counterfeiting, and bioimaging.

Summary: Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.

Abstract The treatment of diabetic wounds faces enormous challenges due to complex wound environments, such as infected biofilms, excessive inflammation, and impaired angiogenesis. The critical role of the microenvironment in the chronic diabetic wounds has not been addressed for therapeutic development. Herein, we develop a microneedle (MN) bandage functionalized with dopamine-coated hybrid nanoparticles containing selenium and chlorin e6 (SeC@PA), which is capable of the dual-directional regulation of reactive species (RS) generation, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), in response to the wound microenvironment. The SeC@PA MN bandage can disrupt barriers in wound coverings for efficient SeC@PA delivery. SeC@PA not only depletes endogenous glutathione (GSH) to enhance the anti-biofilm effect of RS, but also degrades GSH in biofilms through cascade reactions to generate more lethal RS for biofilm eradication. SeC@PA acts as an RS scavenger in wound beds with low GSH levels, exerting an anti-inflammatory effect. SeC@PA also promotes the M2-phenotype polarization of macrophages, accelerating wound healing. This self-enhanced, catabolic and dynamic therapy, activated by the wound microenvironment, provides an approach for treating chronic wounds.

In order to explore the weakening law of mechanical properties of rocks on the top of coalbed methane under high temperature and cyclic loading and unloading, a DDL-200 uniaxial electronic testing machine was used to conduct graded cyclic loading and unloading tests on the rocks, and the weakening laws of mechanical parameters, sound velocity propagation were analyzed. The results show that: at 25-400 ℃, the strain increment is small, the morphological failure is splitting failure, and the internal damage is uneven, and the longitudinal wave velocity propagates quickly; after 400 ℃, the strain increment is large, and the main failure mode is shear failure. The internal debris increases and the pores become larger, the outer layer of the rock has many and irregular fracture surfaces, and the longitudinal wave velocity is slow; during the loading period, the softening coefficient decreases with increasing temperature under the same cycle, and increases with increasing cycle under the same temperature. The degree of deterioration decreases with increasing temperature under the same cycle, and first increases and then decreases with increasing cycle under the same temperature; during the unloading period, the softening coefficient and degradation degree both increase with the increase of the same cycle (or temperature). The research results will provide reference for the stability of the upper rock mass of coal seams during gas mining and the exploration of rocks under complex stress conditions.

Abstract The development of a universal influenza vaccine to elicit broad immune responses is essential in reducing disease burden and pandemic impact. In this study, the mosaic vaccine design strategy and genetic algorithms were utilized to optimize the seasonal influenza A virus (H1N1, H3N2) hemagglutinin (HA) and neuraminidase (NA) antigens, which also contain most potential T-cell epitopes. These mosaic immunogens were then expressed as virus-like particles (VLPs) using the baculovirus expression system. The immunogenicity and protection effectiveness of the mosaic VLPs were compared to the commercial quadrivalent inactivated influenza vaccine (QIV) in the mice model. Strong cross-reactive antibody responses were observed in mice following two doses of vaccination with the mosaic VLPs, with HI titers higher than 40 in 15 of 16 tested strains as opposed to limited cross HI antibody levels with QIV vaccination. After a single vaccination, mice also show a stronger level of cross-reactive antibody responses than the QIV. The QIV vaccinations only elicited NI antibodies to a small number of vaccine strains, and not even strong NI antibodies to its corresponding vaccine components. In contrast, the mosaic VLPs caused robust NI antibodies to all tested seasonal influenza virus vaccine strains. Here, we demonstrated the mosaic vaccines induces stronger cross-reactive antibodies and robust more T-cell responses compared to the QIV. The mosaic VLPs also provided protection against challenges with ancestral influenza A viruses of both H1 and H3 subtypes. These findings indicated that the mosaic VLPs were a promising strategy for developing a broad influenza vaccine in future.

HPAM/PEI gel is a promising material for conformance control in hydrocarbon reservoirs. However, its use in low-permeability reservoirs is limited by the high polymer concentrations present. In this study, the gelation performance of an HPAM/PEI system with HPAM < 2.0 wt.% was systematically investigated. The gelation time for HPAM concentrations ranging from 0.4 to 2.0 wt.% varied from less than 1 h to 23 days, with the highest gel strength identified as grade H. The hydrodynamic radius manifested the primary effect of HPAM on the gelation performance. Branched PEI provided superior gelation performance over linear PEI, and the gelation performance was only affected when the molecular weight of the PEI varied significantly. The optimal number ratio of the PEI-provided imine groups and the HPAM-provided carboxylic acid functional groups was approximately 1.6:1~5:1. Regarding the reservoir conditions, the temperature had a crucial effect on the hydrodynamic radius of HPAM. Salts delayed the gelation process, and the order of ionic influence was Ca2+ > Na+ > K+. The pH controlled the crosslinking reaction, primarily due to the protonation degree of PEI and the hydrolysis degree of HPAM, and the most suitable pH was approximately 10.5. Plugging experiments based on a through-type fracture showed that multi-slug plugging could significantly improve the plugging performance of the system, being favorable for its application in fractured low-permeability reservoirs.

Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel targeting LAG-3 drugs have also been approved in clinical application. With the widespread use of the drug, we must deeply analyze the dilemma of the agents and seek a breakthrough in the treatment prospect. Over the past decades, these agents have demonstrated dramatic efficacy, especially in patients with melanoma and non-small cell lung cancer (NSCLC). Nonetheless, in the field of a broad concept of solid tumours, non-specific indications, inseparable immune response and side effects, unconfirmed progressive disease, and complex regulatory networks of immune resistance are four barriers that limit its widespread application. Fortunately, the successful clinical trials of novel ICB agents and combination therapies, the advent of the era of oncolytic virus gene editing, and the breakthrough of the technical barriers of mRNA vaccines and nano-delivery systems have made remarkable breakthroughs currently. In this review, we enumerate the mechanisms of each immune checkpoint targets, associations between ICB with tumour mutation burden, key immune regulatory or resistance signalling pathways, the specific clinical evidence of the efficacy of classical targets and new targets among different tumour types and put forward dialectical thoughts on drug safety. Finally, we discuss the importance of accurate triage of ICB based on recent advances in predictive biomarkers and diagnostic testing techniques.

Vascular dementia (VD) is a prevalent cognitive disorder among the elderly. Its pathological mechanism encompasses neuronal damage, synaptic dysfunction, vascular abnormalities, neuroinflammation, and oxidative stress, among others. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have garnered significant attention as an emerging therapeutic strategy. Current research indicates that MSC-derived extracellular vesicles (MSC-EVs) play a pivotal role in both the diagnosis and treatment of VD. Thus, this article delves into the recent advancements of MSC-EVs in VD, discussing the mechanisms by which EVs influence the pathophysiological processes of VD. These mechanisms form the theoretical foundation for their neuroprotective effect in VD treatment. Additionally, the article highlights the potential applications of EVs in VD diagnosis. In conclusion, MSC-EVs present a promising innovative treatment strategy for VD. With rigorous research and ongoing innovation, this concept can transition into practical clinical treatment, providing more effective options for VD patients.

Osteoporosis is the result of osteoclast formation exceeding osteoblast production, and current osteoporosis treatments targeting excessive osteoclast bone resorption have serious adverse effects. There is a need to fully understand the mechanisms of osteoclast-mediated bone resorption, identify new drug targets, and find better drugs to treat osteoporosis. Gar C (Gar C) is a major naturally occurring phytochemical isolated from mangosteen, and is a derivative of the naturally occurring phenolic antioxidant lutein. We used an OP mouse model established by ovariectomy (OVX). We found that treatment with Gar C significantly increased bone mineral density and significantly decreased the expression of TRAP, NFATC1 and CTSK relative to untreated OP mice. We found that Garcinone C could disrupt osteoclast activation and resorption functions by inhibiting RANKL-induced osteoclast differentiation as well as inhibiting the formation of multinucleated osteoclasts. Immunoblotting showed that Gar C downregulated the expression of osteoclast-related proteins. In addition, Gar C significantly inhibited RANKL-induced ROS production and affected NF-κB activity by inhibiting phosphorylation Formylation of P65 and phosphorylation and degradation of ikba. These data suggest that Gar C significantly reduced OVX-induced osteoporosis by inhibiting osteoclastogenesis and oxidative stress in bone tissue. Mechanistically, this effect was associated with inhibition of the ROS-mediated NF-κB pathway.

A series of YCe catalysts were prepared using Y-loaded (Y = Cu, Co, Mn) Ce-based metal–organic framework as a precursor. Mn-loaded CeO2 exhibited significantly better catalytic activity in the catalytic oxidation of ethyl acetate (EA) than noble metal catalyst. The relationship between the physicochemical properties of YCe catalysts and catalytic activity was studied by different characterization methods. The enhanced catalytic activity was attributed to the strong interaction between the transition metals and Ce, high specific surface area, abundant lattice defects, more oxygen vacacies and higher Olatt/(Olatt + Oads + Ow) molar ratios. The main intermediates in the oxidation of EA were ethanol, acetic acid, acetone, acetaldehyde and diethyl ether.

Sphingolipid metabolism affects prognosis and resistance to immunotherapy in patients with cancer and is an emerging target in cancer therapy with promising diagnostic and prognostic value. Long noncoding ribonucleic acids (lncRNAs) broadly regulate tumour-associated metabolic reprogramming. However, the potential of sphingolipid metabolism-related lncRNAs in pancreatic adenocarcinoma (PAAD) is poorly understood. In this study, coexpression algorithms were employed to identify sphingolipid metabolism-related lncRNAs. The least absolute shrinkage and selection operator (LASSO) algorithm was used to develop a sphingolipid metabolism-related lncRNA signature (SMLs). The prognostic predictive stability of the SMLs was validated using Kaplan–Meier. Univariate and multivariate Cox, receiver operating characteristic (ROC) and clinical stratification analyses were used to comprehensively assess the SMLs. Gene set variation analysis (GSVE), gene ontology (GO) and tumor mutation burden (TMB) analysis explored the potential mechanisms. Additionally, single sample gene set enrichment analysis (ssGSEA), ESTIMATE, immune checkpoints and drug sensitivity analysis were used to investigate the potential predictive function of the SMLs. Finally, an SMLs-based consensus clustering algorithm was utilized to differentiate patients and determine the suitable population for immunotherapy. The results showed that the SMLs consists of seven sphingolipid metabolism-related lncRNAs, which can well determine the clinical outcome of individuals with PAAD, with high stability and general applicability. In addition, the SMLs-based consensus clustering algorithm divided the TCGA-PAAD cohort into two clusters, with Cluster 1 showing better survival than Cluster 2. Additionally, Cluster 1 had a higher level of immune cell infiltration than Cluster 2, which combined with the higher levels of immune checkpoints in Cluster 1 suggests that Cluster 1 is more consistent with an immune ‘hot tumor’ profile and may respond better to immune checkpoint inhibitors (ICIs). This study offers new insights regarding the potential role of sphingolipid metabolism-related lncRNAs as biomarkers in PAAD. The constructed SMLs and the SMLs-based clustering are valuable tools for predicting clinical outcomes in PAAD and provide a basis for clinical selection of individualized treatments.

The urban thermal environment is closely related to the well-being of many city dwellers. Rich achievements have been obtained for canopy layer urban heat island (CLUHI) studies. Nevertheless, the monitoring and associated factors of CLUHI have not been systematically and timely reviewed. Therefore, this paper aimed to solve this issue to some extent by reviewing the fruitful research progress of CLUHI from the above-mentioned two aspects. The main findings were as follows. (1) Eight methods were adopted to obtain near-surface temperature data for CLUHI research, including four observation, two numerical modeling, remote sensing and data assimilation methods. (2) Air temperature was usually used rather than apparent temperature indices. Obvious differences existed between them, especially under humid hot or cold windy conditions. (3) The CLUHI intensity was generally defined as the differences in temperature between urban and suburban or rural stations or regions by population, land cover/land use, etc, or derived using regression analysis between temperature and impervious surface percentage. (4) The diurnal, monthly, seasonal or interannual variation of CLUHI has been generally analyzed in various global regions. (5) Six types of factors were analyzed, including meteorological conditions, air pollution, socioeconomic factors, urban underlying surface condition, inland or coastal type and landform conditions, and combined effects of some factors. (6) Five potential research directions were proposed, including improvement of data acquisition, sharing and use, considering apparent thermal indices, focus on the rarely studied regions, cities and scales, improving the calculation of CLUHI intensity, and attention to more associated factors and driving force analysis methods. This review can provide references for future CLUHI research and the construction of climate-resilient, livable, low-carbon cities.

Long-chain noncoding small nucleolar RNA host gene 14 (LncRNA SNHG14) is highly expressed in various diseases and promotes diseases progression, but the role and mechanism of LncRNA SNHG14 on targeting miR-137 in promoting osteoarthritis (OA) chondrocyte injury remains unclear. To measure the expression of the LncRNAs SNHG14 and miR-137, cell survival, inflammatory response, chondrocyte apoptosis, and extracellular matrix (ECM) levels, we subjected human chondrocytes to a variety of lipopolysaccharide (LPS) concentrations. To measure the luciferase activity of SNHG14-WT and SNHG14-MUT transfected with miR-137 mimic or miR-NC mimic, luciferase reporter genes were utilized. The results showed that chondrocyte viability was significantly inhibited with LPS treatment and chondrocyte inflammatory response, apoptosis and extracellular matrix degradation were significantly increased. However, the above results were significantly reversed after LncRNA SNHG14 inhibition. The luciferase activity bound to miR-137 was decreased in SNHG14-WT group, but there was no change in SNHG14-mut group, which indicated that LncRNA SNHG14 inhibited miR-137 expression as a miRNA sponge. In conclusion, inhibition of LncRNA SNHG14 attenuates chondrocyte inflammatory response, apoptosis and extracellular matrix degradation by targeting miR-137 in LPS induced chondrocytes.

ObjectivesThe high incidence of abdominal aortic calcification (AAC) is well-documented in individuals with severe renal function decline. However, there is limited research on the historical relationship between estimated glomerular filtration rate (eGFR) and the risk of AAC occurrence in the general population undergoing routine medical examinations. The main objective of this study was to investigate the historical relationship between eGFR and AAC in the general population of the United States.MethodsWe performed a cross-sectional study using the National Health and Nutrition Examination Survey 2013–2014 database. Weighted multivariate linear regression models were used to estimate the associations of eGFR with AAC score. Smooth curve fitting and two-piecewise linear regression were employed to explore the potential non-linear relationship.ResultsA total of 2,978 participant (48.22% were male) aged 40–80 years were included in this study. The fully-adjusted model demonstrated a negative correlation between eGFR and AAC score (β = −0.015, 95% CI: −0.023 to −0.006). However, when applying the smooth curve fitting method, a U-shaped relationship was identified, and the inflection point was calculated at 76.43 ml/min/1.73 m2 using the two-piecewise linear regression model.ConclusionsThere was a U-shaped association between eGFR and AAC score in general US adults, with an inflection point at about 76.43 ml/min/1.73 m2.

A single-nucleotide polymorphism (SNP) rs12252-C of interferon-induced transmembrane protein 3 (IFITM3), resulting in a truncated IFITM3 protein lacking 21 N-terminus amino acids, is associated with severe influenza infection in the Chinese population. However, the effect of IFITM3 rs12252-C on influenza vaccination and the underlying mechanism is poorly understood. Here, we constructed a mouse model with a deletion of 21 amino acids at the N-terminus (NΔ21) of IFITM3 and then compared the antibody response between Quadrivalent influenza vaccine (QIV) immunized wild-type (WT) mice and NΔ21 mice. Significantly higher levels of haemagglutination inhibition (HI) titre, neutralizing antibodies (NAb), and immunoglobulin G (IgG) to H1N1, H3N2, B/Victory, and B/Yamagata viruses were observed in NΔ21 mice compared to WT mice. Correspondingly, the numbers of splenic germinal centre (GC) B cells, plasma cells, memory B cells, QIV-specific IgG+ antibody-secreting cells (ASC), and T follicular helper cells (TFH) in NΔ21 mice were higher compared with WT mice. Moreover, the 21-amino-acid deletion caused IFITM3 translocation from the endocytosis compartment to the periphery of cells, which also prevented the degradation of a co-stimulatory molecule of B cell receptor (BCR) CD81 on the cell surface. More importantly, a more interaction was observed between NΔ21 protein and CD81 compared to the interaction between IFITM3 and CD81. Overall, our study revealed a potential mechanism of NΔ21 protein enhancing humoral immune response by relocation to prevent the degradation of CD81, providing insight into SNP affecting influenza vaccination.

Mg alloys with excellent creep resistance are able to withstand fatigue and damage under high temperature and complex load. Adding alloying elements rather than rare earth elements, such as Mn, can further reduce the cost and thus facilities the widespread applications of Mg alloys. In this paper, the individual effect of Mn and Zr elements on the dynamic microstructural evolution of Mg–Zn alloys during creep is evaluated, on the basis of identical initial microstructure before creep. And the essential origin of Mn substitution for Zr improving the creep resistance of Mg–Zn alloys by one order of magnitude is revealed. Experimental investigations and first principle calculations reveal that prior-precipitation of α-Mn particles serve as the heterogeneous nucleation sites for the precipitation of β1′ phases, and Mn partitioning in MgZn2 phases promote the nucleation and thermal stability of β1′ precipitates during creep. High number density of fine precipitates can effectively inhibit the occurrence of continuous dynamical recrystallization (CDRX), pin dislocations and impede the activation of cross-slip, which are the main reasons for the enhanced creep resistance in ZM60 alloy. As Zr does not participate in the formation of precipitates in ZK60 alloy, the MgZn2 phases with low thermal stability are prone to growth and coarsening during long-term creep. Large number of fine CDRXed grains and sparse coarse precipitates in ZK60 alloy cannot effectively impede the dislocation movement, which contributes to the occurrence of cross-slip and deteriorate the creep resistance. This work provides new insights for designing and fabricating outstanding heat-resistance Mg alloys.

Abstract Objective The objective of this study is to evaluate and compare clinical and virological characteristics of asymptomatic and mild symptomatic patients of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron BA.2.2 variant infection and identify risk factors associated with the prolonged viral negative conversion duration. Methods We conducted a retrospective observational study in a Shanghai (China) Fangcang shelter hospital from April 9 to May 17, 2022. The patient‐related demographic or clinical data were retrospectively recorded. Comparisons of demographic and clinical characteristics between asymptomatic and mild‐symptomatic patients were performed. Cox regression was performed to identify the risk factors of prolonged viral negative conversion duration. Results A total of 551 patients confirmed with SARS‐CoV‐2 Omicron variant infection were enrolled in the study. Of these, 297 patients (53.9%) were asymptomatic and 254 patients (46.1%) had mild symptoms. When comparing the clinical and virological characteristics between the asymptomatic and mild symptomatic groups, several clinical parameters, including age, gender, time to viral clearance from the first positive swab, chronic comorbidities, and vaccination dose did not show statistically significant differences. In mild symptomatic patients, the median viral negative conversion duration (NCD) was 7 days (interquartile range [IQR]: 5–9), which was comparable to the median of 7 days (IQR: 5–10) in asymptomatic patients (p = .943). Multivariate Cox analysis revealed that patients age ≥ 60 years had a significantly higher hazard ratio (HR) for prolonged viral NCD (HR: 1.313; 95% confidence interval: 1.014–1.701, p = .039). Conclusion Asymptomatic and symptomatic patients with non‐severe SARS‐CoV‐2 Omicron BA.2.2 variant infection have similar clinical features and virological courses. Old age was an independent risk factor for prolonged SARS‐CoV‐2 conversion time.

Abstract Cervical cancer is the first identified human papillomavirus (HPV) associated cancer and the most promising malignancy to be eliminated. However, the ever-changing virus subtypes and acquired multiple drug resistance continue to induce failure of tumor prevention and treatment. The exploration of cervical cancer heterogeneity is the crucial way to achieve effective prevention and precise treatment. Tumor heterogeneity exists in various aspects including the immune clearance of viruses, tumorigenesis, neoplasm recurrence, metastasis and drug resistance. Tumor development and drug resistance are often driven by potential gene amplification and deletion, not only somatic genomic alterations, but also copy number amplifications, histone modification and DNA methylation. Genomic rearrangements may occur by selection effects from chemotherapy or radiotherapy which exhibits genetic intra-tumor heterogeneity in advanced cervical cancers. The combined application of cervical cancer therapeutic vaccine and immune checkpoint inhibitors has become an effective strategy to address the heterogeneity of treatment. In this review, we will integrate classic and recently updated epidemiological data on vaccination rates, screening rates, incidence and mortality of cervical cancer patients worldwide aiming to understand the current situation of disease prevention and control and identify the direction of urgent efforts. Additionally, we will focus on the tumor environment to summarize the conditions of immune clearance and gene integration after different HPV infections and to explore the genomic factors of tumor heterogeneity. Finally, we will make a thorough inquiry into completed and ongoing phase III clinical trials in cervical cancer and summarize molecular mechanisms of drug resistance among chemotherapy, radiotherapy, biotherapy, and immunotherapy.

Pulp and paper wastewater (PPWW) contains numerous refractory and harmful contaminants that require advanced treatment to meet the discharge criteria. This study compared the efficacy of two PPWW treatments: ultraviolet/peroxymonosulfate (UV/PMS) and ultraviolet/H2O2 (UV/H2O2) working under similar circumstances. The initial pH value, oxidant dosage, UV radiation intensity, and pseudo-first-order constant kobs were systematically studied in both systems. Optimally, the UV/PMS process produced an effluent of higher quality than the UV/H2O2, as measured by the removal efficiencies of chemical oxygen demand (COD) in 60 min, which were 48.2 and 64.3% for the respective UV/H2O2 and UV/PMS processes and corresponding kobs values of 0.0102 and 0.0159 min−1, respectively. Radical scavenging experiments demonstrated that •OH was the primary reactive oxygen species in UV/H2O2 process, and •OH and SO4−• in the UV/PMS process. Moreover, ultraviolet-visible spectroscopy and gas chromatography coupled mass spectroscopy analyses showed that deep treatment of petroleum hydrocarbons with carbon chain lengths greater than 18 and macromolecular semi-volatile organic compounds in paper wastewater is difficult, whereas the UV/PMS process can significantly improve the removal of amides, esters, phenols, and other aromatic compounds. HIGHLIGHTS UV/PMS is a worthwhile in-depth study to achieve more effective treatment of actual wastewater.; It was difficult to completely degrade the organics in actual PPWW due to some long-chain alkanes and macromolecules containing benzene ring organic substances.;

Abstract Continuous cell division is a hallmark of cancer, and the underlying mechanism is tumor genomics instability. Cell cycle checkpoints are critical for enabling an orderly cell cycle and maintaining genome stability during cell division. Based on their distinct functions in cell cycle control, cell cycle checkpoints are classified into two groups: DNA damage checkpoints and DNA replication stress checkpoints. The DNA damage checkpoints (ATM-CHK2-p53) primarily monitor genetic errors and arrest cell cycle progression to facilitate DNA repair. Unfortunately, genes involved in DNA damage checkpoints are frequently mutated in human malignancies. In contrast, genes associated with DNA replication stress checkpoints (ATR-CHK1-WEE1) are rarely mutated in tumors, and cancer cells are highly dependent on these genes to prevent replication catastrophe and secure genome integrity. At present, poly (ADP-ribose) polymerase inhibitors (PARPi) operate through “synthetic lethality” mechanism with mutant DNA repair pathways genes in cancer cells. However, an increasing number of patients are acquiring PARP inhibitor resistance after prolonged treatment. Recent work suggests that a combination therapy of targeting cell cycle checkpoints and PARPs act synergistically to increase the number of DNA errors, compromise the DNA repair machinery, and disrupt the cell cycle, thereby increasing the death rate of cancer cells with DNA repair deficiency or PARP inhibitor resistance. We highlight a combinational strategy involving PARP inhibitors and inhibition of two major cell cycle checkpoint pathways, ATM-CHK2-TP53 and ATR-CHK1-WEE1. The biological functions, resistance mechanisms against PARP inhibitors, advances in preclinical research, and clinical trials are also reviewed.

As a class of short non-coding ribonucleic acids (RNAs), microRNAs (miRNA) regulate gene expression in human cells and are expected to be nucleic acid drugs to regulate and treat a variety of biological processes and diseases. However, the issues with potential materials toxicity, quantity production, poor cellular uptake, and endosomal entrapment limit their further applications in clinical practice. Herein, ZIF-8, a metal-organic framework with noncytotoxic zinc (II) as the metal coordination center, was selected as miRNA delivery vector was used to prepare miR-200c-3p@ZIF-8 in one step by Y-shape microfluidic chip to achieve intracellular release with low toxicity, batch size, and efficient cellular uptake. The obtained miR-200c-3p@ZIF-8 was identified by TEM, particle size analysis, XRD, XPS, and zeta potential. Compared with the traditional hydrothermal method, the encapsulation efficiency of miR-200c-3p@ZIF-8 prepared by the microfluidic method is higher, and the particle size is more uniform and controllable. The experimental results in cellular level verified that the ZIF-8 vectors with low cytotoxicity and high miRNAs loading efficiency could significantly improve cellular uptake and endosomal escape of miRNAs, providing a robust and general strategy for nucleic acid drug delivery. As a model, the prepared miR-200c-3p@ZIF-8 is confirmed to be effective in osteoarthritis treatment.

TRPV1 channel agonists and antagonists, which have powerful analgesic effects without the addictive qualities associated with traditional analgesics, have become a focus area for the development of novel analgesics. In this study, quantitative structure–activity relationship (QSAR) models for three bioactive endpoints (Ki, IC50, and EC50) were successfully constructed using four machine learning algorithms: SVM, Bagging, GBDT, and XGBoost. These models were based on 2922 TRPV1 modulators and incorporated four types of molecular descriptors: Daylight, E-state, ECFP4, and MACCS. After the rigorous five-fold cross-validation and external test set validation, the optimal models for the three endpoints were obtained. For the Ki endpoint, the Bagging-ECFP4 model had a Q2 value of 0.778 and an R2 value of 0.780. For the IC50 endpoint, the XGBoost-ECFP4 model had a Q2 value of 0.806 and an R2 value of 0.784. For the EC50 endpoint, the SVM-Daylight model had a Q2 value of 0.784 and an R2 value of 0.809. These results demonstrate that the constructed models exhibit good predictive performance. In addition, based on the model feature importance analysis, the influence between substructure and biological activity was also explored, which can provide important theoretical guidance for the efficient virtual screening and structural optimization of novel TRPV1 analgesics. And subsequent studies on novel TRPV1 modulators will be based on the feature substructures of the three endpoints.

Objective To investigate the clinicopathological features, diagnosis and differential diagnosis of mixed skin tumor. Methods We retrospectively analyzed the data of 18 patients with mixed skin tumors from our department from March 2017 to September 2021. Results The male to female ratio of the 18 cases was 1 ∶1, with the onset age of 24 to 64 years. All patients had facial involvement (most common on the nose), and exhibited asymptomatic singular nodule in light red or skin color. The histological findings revealed mixed skin tumor, including differentiation toward eccrine glands in 3 cases and apocrine glands in 15 cases. None of the 18 patients was clinically diagnosed as mixed skin tumor. All 18 patients underwent surgical resection and were followed up for 2 months to 1 year without recurrence. Conclusions Mixed skin tumor is a rare benign tumor. The diagnosis of the disease is mainly dependent on histopathological examination.

Recurrent glomerulonephritis after renal transplantation is the third most common cause of allograft loss, the most frequent of which is associated with IgA nephropathy (IgAN). This study aims to provide a systematic review of the risk factors associated with recurrent IgAN after renal transplantation. We searched English and Chinese databases, including PubMed, Embase, Web of Science, CNKI, and others, and included all case-control studies involving risk factors for recurrent IgAN after renal transplantation from the databases’ establishment to March 2022. Data were analyzed using the Stata 12.0. A total of 20 case–control studies were included in the meta-analysis, with 542 patients with recurrent IgAN and 1385 patients without recurrent IgAN. The results showed that donor age (standardized mean difference [SMD] -0.13 [95% CI -0.26, -0.001]; P = 0.048), patient age at transplantation (SMD -0.41 [95% CI -0.53, -0.29]; P < 0.001), time from diagnosis to end-stage renal disease (SMD -0.42 [95% CI -0.74, -0.10]; P = 0.010), previous transplantation (odds ratio [OR] 1.73 [95% CI 1.06, 2.81]; P = 0.027), living donor (OR 1.86 [95% CI 1.34, 2.58]; P < 0.001), related donor (OR 2.64, [95% CI 1.84, 3.79]; P < 0.001), tacrolimus use (OR 0.71 [95% CI 0.52, 0.98]; P = 0.035), basiliximab use (OR 0.39 [95% CI 0.27, 0.55]; P < 0.001), proteinuria (SMD 0.42 [95% CI 0.13, 0.71]; P = 0.005) and serum IgA level (SMD 0.48 [95% CI 0.27, 0.69]; P < 0.001) were associated with recurrent IgAN after renal transplantation. In general, tacrolimus and basiliximab use were protective factors against recurrent IgAN after renal transplantation, whereas donor age, patient age at transplantation, time from diagnosis to end-stage renal disease, previous transplantation, living donor, related donor, proteinuria, and serum IgA level were risk factors for recurrent IgAN after renal transplantation. Clinical decision making should warrant further consideration of these risk factors.

cGAS senses viral DNA and forms cytosolic cGAS-DNA granules to mediate anti-DNA viral signaling pathway. Here the authors show that PCBP2 interacts with cGAS and antagonizes condensation of cGAS-DNA granules, thus maintaining host immune homeostasis.

Abstract Wear particle-induced periprosthetic osteolysis (PPO) have become a major reason of joint arthroplasty failure and secondary surgery following joint arthroplasty and thus pose a severe threat to global public health. Therefore, determining how to effectively suppress particle-induced PPO has become an urgent problem. The pathological mechanism involved in the PPO signaling cascade is still unclear. Recently, the interaction between osteogenic inhibition and wear particles at the implant biological interface, which has received increasing attention, has been revealed as an important factor in pathological process. Additionally, Hedgehog (Hh)-Gli1 is a crucial signaling cascade which was regulated by multiple factors in numerous physiological and pathological process. It was revealed to exert a crucial part during embryonic bone development and metabolism. However, whether Hh-Gli1 is involved in wear particle-induced osteogenic inhibition in PPO remains unknown. Our present study explored the mechanism by which the Hh-Gli1 signaling cascade regulates titanium (Ti) nanoparticle-induced osteolysis. We found that Hh-Gli1 signaling was dramatically downregulated upon Ti particle treatment. Mechanistically, glycogen synthesis kinase 3β (GSK-3β) activation was significantly increased in Ti particle-induced osteogenic inhibition via changes in GSK-3β phosphorylation level and was found to participate in the posttranslational modification and degradation of the key transcription factor Gli1, thus decreasing the accumulation of Gli1 and its translocation from the cytoplasm to the nucleus. Collectively, these findings suggest that the Hh-Gli1 signaling cascade utilizes a GSK3β-mediated mechanism and may serve as a rational new therapeutic target against nanoparticle-induced PPO. Graphical Abstract

In recent years, the widespread application of artificial intelligence algorithms in protein structure, function prediction, and de novo protein design has significantly accelerated the process of intelligent protein design and led to many noteworthy achievements. This advancement in protein intelligent design holds great potential to accelerate the development of new drugs, enhance the efficiency of biocatalysts, and even create entirely new biomaterials. Protein characterization is the key to the performance of intelligent protein design. However, there is no consensus on the most suitable characterization method for intelligent protein design tasks. This review describes the methods, characteristics, and representative applications of traditional descriptors, sequence-based and structure-based protein characterization. It discusses their advantages, disadvantages, and scope of application. It is hoped that this could help researchers to better understand the limitations and application scenarios of these methods, and provide valuable references for choosing appropriate protein characterization techniques for related research in the field, so as to better carry out protein research.

The present work introduces a laser-induced cavitation bubble technique for forming an axisymmetric structure (i.e., microgroove) and the dynamics of a cavitation bubble from initial expansion to the collapse stages that were also simulated. Furthermore, the shock wave signals and dynamic properties of the cavitation bubble were recorded using a hydrophone and a high-speed camera. The experiments on microgrooves formed by laser-induced cavitation bubble stamping were carried out, and the effects of laser energy, the initial position of the bubble, and the number of impacts on the microformability of aluminum sheets are discussed. The depth of the microgroove was investigated using experiments, and it was found that the process can serve as a rapid technique for impressing microfeatures on thin-sheet metals. The experimental results showed that as the initial position of the bubble increased, the deformation depth decreased. As the laser energy and number of impacts increased, the deformation depth increased. The results of the response surface experiments showed that a laser energy of 27 mJ, 3 impacts, and a bubble position of 3 mm were optimal for the process. By using the optimal parameters, flat and smooth microgrooves with a forming depth of 102.54 µm were successfully fabricated. Furthermore, the maximum thickness thinning of the microgroove section occurred at the entrance areas, and this area had the greatest hardness. This also indicated that the greatest amount of plastic deformation of the material and grain refinement occurred in this area. On the other hand, the aluminum foil did not undergo oxidation during the plastic deformation process. These results demonstrated that laser-induced bubble stamping is an advanced micromachining method with promising applications.

Maternal RNA degradation is critical for embryogenesis and is tightly controlled by maternal RNA-binding proteins. Here the authors show that a subset of m6A-modified mRNAs regulates the dynamics of RNA-granules, thus contributes to maternal mRNA decay.

Vehicular ad hoc networks (VANETs) are the communication foundation for future intelligent transportation systems and guarantee safe driving of intelligent networked vehicles. Moreover, VANETs face a series of security challenges related to the protection of vehicle privacy, authenticity of transmitted information, and bandwidth limitations. To resolve these contradictions, many certificateless aggregate signature (CLAS) schemes have been proposed. However, the majority of them can neither resist malicious-but-passive key generation center attacks, replay attacks, and link attacks, nor track the actual identities of malicious vehicles. Meanwhile, the security of previous CLAS schemes in VANETs is only formally provided in the random oracle model (ROM), which might be insecure in actual implementation. In addition, most CLAS schemes still have problems of large verification delays and high communication overhead. To address the above-mentioned problems, a new conditional privacy-preserving CLAS scheme in VANETs is proposed, which adopts full aggregation technology to reduce computation and bandwidth resources. According to the formal security proofs under the computational Diffie-Hellman problem (CDHP) given in the standard model (SM), the security level of this scheme is higher than that of other CLAS schemes under ROM in practical applications. Additionally, the use of pseudonym mechanism realizes conditional privacy protection in VANETs. The performance analysis shows that this scheme has a higher efficiency in terms of computation and communication overhead compared with several previous CLAS schemes.

It has been reported that inhibition of GPR65 may be effective for the treatment of certain cancers. Nevertheless, the role of GPR65 in various cancers remains unknown. We conducted an exhaustive pan-cancer analysis of GPR65 using multiple databases, including TCGA, GTEx, BioGPS, HPA, cBioPortal, and GeneCards. GPR65 was found to be differentially expressed in various cancers and linked to tumor mutational burden (TMB), microsatellite instability (MSI), and Ploidy, playing a key function in the tumor microenvironment (TME). It is closely linked to the development of Th17 cells as well as Th1 and Th2 cells in certain cancers. Our findings indicate that the expression of GPR65 is highly linked with clinical prognosis, mutations, and immune cell infiltration. It was revealed as an indicator of patient prognosis as well as a possible immunomodulatory role. As a possible new immunological checkpoint, GPR65 could be a target for tumor immunotherapy.

As the total mileage of roads with asphalt concrete pavement is increasing rapidly, using ground-penetrating radar (GPR) to estimate the dimension of internal distresses of the asphalt pavement is of great significance for pavement maintenance. However, the relationship between the dimension of road distress and the characteristics of road distress’s radar echo has not been quantified. Therefore, in this paper, a GPR forward modeling toward base cracks and interlayer voids is conducted to investigate the relationship, and a model test is conducted to verify the forward modeling. The results indicate that it is feasible to use a GPR image to estimate the dimension of interlayer voids and base cracks. For vertical dimension estimation, the vertical dimension of the distressed area has a positive relationship with the difference in the return time of radar echoes from the top and bottom of the distressed area. However, the area’s vertical dimension must be at least a quarter of the length of the electromagnetic wave used in the GPR to be correctly identified. Otherwise, it is not easy to distinguish the overlapping echoes from each other. For horizontal dimension estimation, the base crack’s horizontal dimension has a quadratic correlation with the echo’s amplitude, and the horizontal dimension of an interlayer void is approximately equal to the length of its echo’s flat segment.

Power battery test equipment is widely used to produce and test new energy vehicles and storage containers. To address the problem of DC bus voltage fluctuations that affect the accuracy of output voltage and current, a high-accuracy bus voltage control strategy is based on nonlinear extended state observation (NLESO) and terminal silding mode controller (TSMC) load current estimation. Simulation and experimental results show that the control strategy has a good suppression effect on the DC bus voltage fluctuation and can effectively improve the accuracy of the DC side output voltage and current. Grid voltage differential feedforward is adopted, which can achieve fast suppression of DC bus voltage fluctuations in power battery test equipment and meet the high precision output requirements of the system DC bus.

Macrophages have crucial roles in the pathogenesis of rheumatoid arthritis (RA). We aimed to elucidate the temporal profile of macrophage infiltration in synovitis in RA rat models using PET (positron emission tomography) imaging based a new generation of TSPO (Translocator protein, 18 kDa)-PET ligand, 18F-VUIIS1008 {2-[5,7-Diethyl-2-{4-[2-(18F)fluoroethoxy]phenyl}pyrazolo(1,5-a)pyri-midin-3-yl]-N, N-diethylacetamide}. In vitro and in vivo studies were conducted using RAW264.7 macrophage cells and a rat model of RA induced by Complete Freund’s Adjuvant (CFA). Our results showed 18F-VUIIS1008 showed excellent stability in vitro and binding specificity to RAW264.7 cells, and rapid accumulation in the left inflammatory ankles. PET studies revealed that 18F-VUIIS1008 could clearly identify the left inflammatory ankles with good contrast at 30–120 min post-injection. The uptake of 18F-VUIIS1008 of left inflammatory ankles was a wiggle trace with two peaks on day 7 and 29, and then, the highest peak uptake was seen on day 29 (3.00% ± 0.08%ID/g) at 60 min after injection. Tracer uptakes could be inhibited by PK11195 or VUIIS1008. Immunohistochemistry and immunofluorescence tests showed that elevated TSPO expression and infiltrated macrophages were found in the left inflammation ankles. 18F-VUIIS1008 as a novel PET imaging agent showed great potential to identify temporal profile of macrophage infiltration in synovitis in RA, and deliver accurate non-invasive diagnosis and real-time monitoring of RA development.

Background: Hepatocellular carcinoma (HCC) is a malignancy with a poor prognosis. This study aimed to distinguish patients with HCC having distinct tumour immune microenvironment (TIME) features and construct an immune-related gene signature (IRGs) to assess prognosis and provide a basis for personalised therapies.Methods: Transcriptomic data of patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We assessed the immune cell infiltration in each HCC specimen using single sample gene set enrichment analysis (ssGSEA) and classified all patients with HCC into high- and low-immune clusters using a hierarchical clustering algorithm. The ESTIMATE and CIBERSORT computational methods were employed to verify the stability and effectiveness of the immune clusters. Subsequently, the differentially expressed genes (DEGs) of the high- and low-immune clusters and the immune-related genes intersected to obtain the immune-related DEGs. The least absolute shrinkage and selection operator (LASSO) was then employed to screen the optimal genes for the construction of a prognostic predictive signature and to divide patients into high- and low-risk subgroups. The predictive efficacy of the IRGs was further confirmed using Kaplan–Meier survival curves, univariate and multifactorial Cox regression and time-dependent ROC curves in the TCGA and GSE14520 validation cohorts. Furthermore, we developed a nomogram to predict the prognosis. Tumour mutation burden (TMB) was also analysed in the risk groups. Additionally, gene ontology and gene set variation analysis were used for biological function and pathway exploration. Lastly, drug sensitivity analyses were employed to investigate prospective therapeutics in the two risk populations.Results: Immune cluster analysis based on ssGSEA could well distinguish the TIME characteristics of patients with HCC. The stromal score, immune score and ESTIMATE score were all lower in the low-immune cluster. Meanwhile, most of the immune checkpoint-related genes and HLA family genes were overexpressed in the high-immune cluster, suggesting that this cluster could be a beneficial population for immune checkpoint inhibitors therapy. There were 1,617 DEGs between the two immune clusters, of which 414 genes intersected with immune-associated genes. Furthermore, Cox regression analysis revealed 49 DEGs that were associated with survival. Then, 19 DEGs were screened using the LASSO algorithm for IRGs construction and patients were classified into high- and low-risk groups. Both the constructed signature and nomogram had good prognostic predictive efficacy. The signature-based risk score was an independent prognostic predictor in both the TCGA and GSE14520 cohorts. Additionally, there was no significant difference in TMB between the two risk populations. Lastly, the half-maximal inhibitory concentrations of certain chemotherapeutic and targeted therapeutic agents differed between the two risk groups.Conclusion: Our study provides a personalized tool for predicting the prognosis and TIME landscape of HCC and a basis for developing personalised treatment regimens.

Vaccination is the most effective means of protecting people from influenza virus infection. The effectiveness of existing vaccines is very limited due to antigenic drift of the influenza virus. Therefore, there is a requirement to develop a universal vaccine that provides broad and long-lasting protection against influenza. CD8+ T-cell response played a vital role in controlling influenza virus infection, reducing viral load, and less clinical syndrome. In this study, we optimized the HA sequences of human seasonal influenza viruses (H1N1, H3N2, Victoria, and Yamagata) by designing multivalent vaccine antigen sets using a mosaic vaccine design strategy and genetic algorithms, and designed an HA mosaic cocktail containing the most potential CTL epitopes of seasonal influenza viruses. We then tested the recombinant mosaic antigen, which has a significant number of potential T-cell epitopes. Results from genetic evolutionary analyses and 3D structural simulations demonstrated its potential to be an effective immunogen. In addition, we have modified an existing neutralizing antibody-based seasonal influenza virus vaccine to include a component that activates cross-protective T cells, which would provide an attractive strategy for improving human protection against seasonal influenza virus drift and mutation and provide an idea for the development of a rationally designed influenza vaccine targeting T lymphocyte immunity.