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In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.

Background: Anaplastic thyroid carcinoma (ATC), a rare but highly aggressive endocrine malignancy, is characterized by a significant presence of cancer stem-like cells (CSCs). These CSCs, known for their self-renewal and differentiation capacities, contribute to various aggressive tumor properties, including recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Despite their critical role, the regulatory mechanisms of CSCs in ATC remain poorly elucidated, posing challenges in effectively targeting these cells for treatment. Methods: To delve into this, we employed the single sample gene set enrichment analysis (ssGSEA) algorithm to evaluate the stemness of samples in combined datasets. Samples were then classified into high and low stemness subgroups based on their average stemness scores. Differential gene expression between these subgroups was analyzed. We further explored the association of candidate genes with patient prognosis. Additionally, we conducted gene set enrichment analysis (GSEA) and a series of cell biology experiments to validate the role of DEP domain-containing protein 1 (DEPDC1) in fostering CSC-like traits and regulating the malignant phenotypes of ATC. Results: Our investigation demonstrated that DEPDC1 was significantly upregulated in CSCs and is abundantly expressed in ATC tissues. In vitro assays revealed that knockdown of DEPDC1 markedly inhibited tumor sphere formation and attenuated the proliferation, invasion, and migration of ATC cells. This silencing also resulted in reduced expression of stemness markers associated with CSCs. Furthermore, our GSEA findings linked high DEPDC1 expression to cell cycle progression and the maintenance of tumor cell stemness, with DEPDC1 knockdown disrupting these signaling pathways. Collectively, our results position DEPDC1 as a pivotal regulator of CSC-like characteristics in ATC, where aberrant DEPDC1 expression amplifies stemness properties and fuels the cancer's aggressive behavior. Consequently, DEPDC1 emerges as a promising therapeutic target for ATC management. In summary, this study underscores the pivotal role of DEPDC1 in modulating CSC-like features in ATC, offering new avenues for targeted therapy in this challenging malignancy.

Currently, the research agenda of energy transition is gaining momentum. This paper conducts a comprehensive review of this body of research by presenting a framework that describes the connotations, mechanisms, and effects of energy transitions. The study concludes that the energy transition will lead to the reconstruction of energy system elements beyond the energy sector, with the dual connotations of explicit transition and implicit transition. The explicit transition is usually captured by statistic data and information, for instance, energy utilization type, structure, form, transportation mode, and spatial pattern. The implicit transition involves shifts in energy security, geopolitical structure, energy power, energy justice, and energy governance, which receives relatively less attention in current literature. The energy transition is a highly socialized process, driven by many intertwined factors such as technological innovation, market mechanisms, policy arrangements, and sociocultural factors, triggering profound socio-economic and ecological effects. Looking ahead, it is urgent to pay attention to the multi-scale effects of energy transition, avoid the risks brought by energy transition, and ultimately achieve just energy transition. This paper provides a novel perspective and contributes to the literature on theoretical understanding and advancement of energy transition.

BackgroundLight influences the secretion of melatonin in the body and regulates circadian rhythms, which play an important role in sleep and mood. The light level of rooms in long-term care facilities is usually far below the threshold required to regulate the body’s circadian rhythm, and insufficient light can easily lead to sleep and mood disturbances among older residents in nursing homes. Therefore, the objective of this study was to investigate the effects of light therapy on sleep and circadian rhythm in older adults with type 2 diabetes residing in long-term care facilities.MethodsThis study was a prospective, single-blind, randomized controlled trial. Participants were randomly assigned to either the light therapy (LT) group or the control group and received the intervention for four weeks. Primary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and objective sleep parameters recorded by a sleep monitoring bracelet, Morningness-Eveningness Questionnaire (MEQ). The secondary outcome included glycated serum protein (GSP). Data was collected at three time points: at baseline (T0), immediate post-treatment (T1), and 4-week follow-up (T2). A linear mixed model analysis was used to analyzed the data.ResultsWe enrolled 45 long-term care residents. Compared with the control group, significant reductions in PSQI scores were observed at T1 and T2. At T2, the sleep score of objective sleep parameters was significantly higher in the LT group compared to the control group. Additionally, compared to the baseline T0, MEQ scores were significantly lower in the LT group at T1 and T2, with no significant difference in the control group. There was no significant difference between groups in glycated serum protein values at T1 and T2. However, compared to T0, glycated serum protein values decreased in the LT group while increased in the control group at T2.ConclusionLight therapy had a positive effect on subjective sleep quality and circadian rhythm time type in long-term care residents with type 2 diabetes, and had a possible delayed effect on objective sleep. However, no discernible alterations in blood glucose levels were detected in this study.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by dopaminergic neuron death in the substantia nigra, leading to motor dysfunction. Autophagy dysregulation has been implicated in PD pathogenesis. This study explores the role of miR-214–3p in PD, focusing on its impact on autophagy and dopaminergic neuron viability. Using in vitro and in vivo models, we demonstrate that miR-214–3p inhibits autophagy and promotes dopaminergic neuron apoptosis. Behavioral assessments and molecular analyses reveal exacerbation of PD symptoms upon miR-214–3p overexpression. Furthermore, mechanistic investigations identify ATG3 as a target, shedding light on miR-214–3p's regulatory role in autophagy. These findings enhance our understanding of PD pathogenesis and propose miR-214–3p as a potential biomarker and therapeutic target for modulating autophagy and neuronal survival in PD.

Background: Various studies highlighted that immune cell-mediated inflammatory processes play crucial roles in the progression and treatment of hepatocellular carcinoma (HCC). However, the immune microenvironment of HCC is still poorly characterized. Exploring the role of immune-related genes (IRGs) and describing the immune landscape in HCC would provide insights into tumor-immune co-evolution along HCC progression. Methods: We integrated the datasets with complete prognostic information from the Cancer Genome Atlas (TCGA) database and GEO DataSets (GSE14520, GSE76427, and GSE54236) to construct a novel immune landscape based on the Cibersort algorithm and reveal the prognostic signature in HCC patients. Results: To describe the tumor microenvironment (TME) in HCC, immune infiltration patterns were defined using the CIBERSORT method, and a prognostic signature contains 5 types of immune cells, including 3 high-risk immune cells (T.cells. CD4. memory. resting, Macrophages.M0, Macrophages.M2) and 2 low-risk immune cells (Plasma. cells, T.cells.CD8), were finally constructed. A novel prognostic index, based on prognostic immune risk score (pIRG), was developed using the univariate Cox regression analyses and LASSO Cox regression algorithm. Furthermore, the ROC curve and KM curve showed that the TME signatures had a stable value in predicting the prognosis of HCC patients in the internal training cohort, internal validation, and external validation cohort. Differential genes analysis and qPCR experiment showed that the expression levels of AKR1B10, LAPTM4B, MMP9, and SPP1 were significantly increased in high-risk patients, while the expression of CD5L was lower. Further analysis found that AKR1B10 and MMP9 were associated with higher M0 macrophage infiltration, while CD5L was associated with higher plasma cell infiltration. Conclusions: Taken together, we performed a comprehensive evaluation of the immune landscape of HCC and constructed a novel and robust prognostic prediction model. AKR1B10, LAPTM4B, MMP9, SPP1, and CD5L were involved in important processes in the HCC tumor microenvironment and were expected to become HCC prediction markers and potential targets of treatment.

Conclusion: In addition to drug treatment, cardiac rehabilitation guided by CPET can effectively improve blood pressure control, reduce blood pressure variability, improve cardiorespiratory function and lipid metabolism, and increase exercise endurance in patients with Grade 1 hypertension. Its efficacy is clear and safe, with clinical value for promotion.

Abstract Background One‐carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic pathways, including nucleotide metabolism, amino acid metabolism, cellular redox defence and epigenetic maintenance. At present, 1C metabolism is considered the hallmark of cancer. The 1C units obtained from the metabolic pathways increase the proliferation rate of cancer cells. In addition, anticancer drugs, such as methotrexate, which target 1C metabolism, have long been used in the clinic. In terms of immunotherapy, 1C metabolism has been used to explore biomarkers connected with immunotherapy response and immune‐related adverse events in patients. Methods We collected numerous literatures to explain the roles of one‐carbon metabolism in cancer immunotherapy. Results In this review, we focus on the important pathways in 1C metabolism and the function of 1C metabolism enzymes in cancer immunotherapy. Then, we summarise the inhibitors acting on 1C metabolism and their potential application on cancer immunotherapy. Finally, we provide a viewpoint and conclusion regarding the opportunities and challenges of targeting 1C metabolism for cancer immunotherapy in clinical practicability in the future. Conclusion Targeting one‐carbon metabolism is useful for cancer immunotherapy.

Electrically heated tobacco products (EHTPs) could release effective aerosol components from tobacco materials at relatively low temperatures without a burning phenomenon. It is essential to grasp the temperature distribution and release mechanism of key components in heated tobacco materials. The existing experimental studies have provided initial insights into the thermodynamic behavior of tobacco materials under various conditions. However, current numerical models are still in their early stages of development, with the majority failing to correlate heat transfer with component release. Based on this, a coupled numerical model of gas flow, heat transfer, and the release of key components in the electrically heated tobacco product is established in this study, which exhibits improvements in revealing the internal heat and mass transfer characteristics in the porous media of tobacco and is capable of evaluating the influence of component contents and product design parameters. The release rates of water, glycerol, and nicotine components are quantitatively described by the first-order Arrhenius formula, and the transport of heat and gas flow is simulated using the Navier-Stokes equation. The accuracy of the model is validated through experiments, including temperature monitoring at multiple measurement points and determination of residual contents in the tobacco substrate after each puff. The simulation results suggest that an appropriate component ratio and tobacco filler mass can enhance both the release amount and release efficiency of key components, and reducing either the diameter or length of the tobacco section can help to improve the heat transfer performance. A slower heating rate matched with longer preheating times enables the complementary release of water and glycerol components, which helps to regulate the uniformity of component content in the aerosol to some extent. This study helps to provide suggestions for the design and optimization of electrically heated tobacco products.

When the weather is cold and wet, the insulator and the transmission line components often undergo icing. In order to study the inhibition effect of the compression arc-extinguishing device with icing on the recovery of arc plasma conductivity and air disruptive strength, this paper will verify it through simulation and test. In the simulation part, a two-dimensional geometric model is established, and the magnetohydrodynamic equation group is used as the control equation group. The breakdown characteristics of the device with and without icing are compared, and the dynamic characteristics of the arc are studied in terms of temperature and conductivity. The results show that the temperature of the arc plasma can be reduced to 3000 K within 1 ms, and the conductivity can be reduced to 0 within 250 µs. In the test part, the suppression effect on arc current amplitude after the device with icing is subjected to high current impact is verified, and the coupling triggering method of impulse voltage and power frequency voltage is adopted to further verify the arc extinguishing condition of the device when the power frequency current continues. The results show that the amplitude of the arc produced by high current impulse decreases from 67 to 35 kA and to 0 within 1 ms after passing through the device with icing, and the current amplitude can still drop to 0 at 2.5 ms after adding the power frequency voltage. It is proved that the device with icing can inhibit the recovery of arc plasma conductivity and air disruptive strength.

This paper proposes a wave–photovoltaic-battery hybrid power generation platform which based on the distributed DC collection and AC inverter grid structure. To be able to simplify the control structure of the power generation system and improve the anti-interference ability of the system, a one-step delay compensation model predictive current control (MPCC) method is proposed for the wave power generation rectifier unit and the perturbation and observation (P&O) fuzzy logic maximum power point tracking (MPPT) algorithm is applied in the photovoltaic power generation unit. Meanwhile, the constant power control method is used to realize the charge and discharge control of the energy storage system to achieve the grid-connected goal of tracking the load power demand. Finally, the MATLAB/Simulink software is applied to simulate the grid-connected operation characteristics of the wave energy power generation unit in continuous power generation modes, as well as the photovoltaic power generation unit at constant temperature and variable irradiance. The results illustrate that the suggested technique for controlling the power generating unit is straightforward and feasible, DC bus voltage stability effect is effective, and the inverter output satisfies the grid-connected operating requirement, which verifies the feasibility of the proposed scheme and can provide some theoretical support for the subsequent high-capacity wave–photovoltaic-battery hybrid power generation platform.

Abstract Background Since the Non-pharmaceutical Intervention (NPI) by COVID-19 emerged, influenza activity has been somewhat altered. Objectives The aim of this study was to explore changes in influenza activities in the context of COVID-19 based on the sentinel hospitals/units in Guangdong, southern China. Methods The surveillance data in influenza-like illness (ILI) were collected from 21 cities in Guangdong between September 2017 and August 2021, while 43 hospitals/units were selected to analyze the predominant types of influenza, population characteristics, and seasonal features by three methods (the concentration ratio, the seasonal index, and the circulation distribution), based on a descriptive epidemiological approach. Results During the four consecutive influenza seasons, a total of 157345 ILIs were tested, of which 9.05% were positive for influenza virus (n = 14238), with the highest positive rates for both IAV (13.20%) and IBV (5.41%) in the 2018–2019 season. After the emergence of COVID-19, influenza cases decreased near to zero from March 2020 till March 2021, and the dominant type of influenza virus changed from IAV to IBV. The highest positive rate of influenza existed in the age-group of 5 ~

Abstract Background Gastric cancer is a highly heterogeneous disease, which makes it challenging to develop effective targeted therapies. Although the potassium voltage‐gated channel subfamily D (KCND) channels, particularly KCND2 (also known as Kv4.2), have found evidence of involvement in the occurrence and development of various cancers, there are still some limitations in our understanding of KCND2's roles in gastric cancer. Methods We analyzed the correlation between KCND2 expression and clinical features as well as immune infiltration using the Cancer Genome Atlas (TCGA) database. Functional assays of KCND2 were conducted using Cell counting Kit‐8 (CCK8), clone formation assay and cell cycle analysis. Additionally, immunofluorescence, flow cytometry and quantitative real‐time polymerase chain reaction (qRT‐PCR) techniques were used to investigate tumor proliferation and immune cell infiltration at different levels of KCND2 expression in vivo. Results KCND2 was markedly elevated in gastric cancer and its expression appeared to link to different grades, T stages, and N stages. In addition, KCND2 was an independent predictor of prognosis, and its elevated levels in TCGA database revealed a more unfavorable prognosis for patients with gastric cancer. KCND2 strengthened the viability at the cellular level by boosting the proliferation of gastric cancer cells and reducing their death rate. Additionally, it also highlights that KCND2 the abilities of proliferating of gastric cancer cells by stimulating NF‐κB both in cell and animal levels. In addition, the findings provided proof that in animal levels, KCND2 might regulate the immune system by associating with promoting M2 macrophages, which are known to play critical roles in cancer progression. Mechanistically, KCND2 was found to lead to the infiltration of M2 macrophages through activation of NF‐κB, ultimately promoting the advancement of gastric cancer. Conclusion Overall, these findings suggest that KCND2 is likely to be available as an underlying therapeutic target for gastric cancer.

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

Abstract Background Anaplastic thyroid carcinoma (ATC) was a rare and extremely malignant endocrine cancer with the distinct hallmark of high proportion of cancer stem cell-like characteristics. Therapies aiming to cancer stem-like cells (CSCs) were emerging as a new direction in cancer treatment, but targeting ATC CSCs remained challenging, mainly due to incomplete insights of the regulatory mechanism of CSCs. Here, we unveiled a novel role of ISG15 in the modulation of ATC CSCs. Methods The expression of ubiquitin-like proteins were detected by bioinformatics and immunohistochemistry. The correlation between ISG15 expression and tumor stem cells and malignant progression of ATC was analyzed by single-cell RNA sequence from the Gene Expression Omnibus. Flow cytometry combined with immunofluorescence were used to verify the enrichment of ISG15 and ISGyaltion in cancer stem cells. The effect and mechanism of ISG15 and KPNA2 on cancer stem cell-like characteristics of ATC cells were determined by molecular biology experiments. Mass spectrometry combined with immunoprecipitation to screen the substrates of ISG15 and validate its ISGylation modification. Nude mice and zebrafish xenograft models were utilized to demonstrate that ISG15 regulates stem cell characteristics and promotes malignant progression of ATC. Results We found that among several ubiquitin proteins, only ISG15 was aberrantly expressed in ATC and enriched in CSCs. Single-cell sequencing analysis revealed that abnormal expression of ISG15 were intensely associated with stemness and malignant cells in ATC. Inhibition of ISG15 expression dramatically attenuated clone and sphere formation of ATC cells, and facilitated its sensitivity to doxorubicin. Notably, overexpression of ISGylation, but not the non-ISGylation mutant, effectively reinforced cancer stem cell-like characteristics. Mechanistically, ISG15 mediated the ISGylation of KPNA2 and impeded its ubiquitination to promote stability, further maintaining cancer stem cell-like characteristics. Finally, depletion of ISG15 inhibited ATC growth and metastasis in xenografted mouse and zebrafish models. Conclusion Our studies not only provided new insights into potential intervention strategies targeting ATC CSCs, but also uncovered the novel biological functions and mechanisms of ISG15 and ISGylation for maintaining ATC cancer stem cell-like characteristics. Graphical Abstract

Abstract The initial operation of a light-emitting electrochemical cell (LEC) constitutes the in-situ formation of a p–n junction doping structure in the active material by electrochemical doping. It has been firmly established that the spatial position of the emissive p–n junction in the interelectrode gap has a profound influence on the LEC performance because of exciton quenching and microcavity effects. Hence, practical strategies for a control of the position of the p–n junction in LEC devices are highly desired. Here, we introduce a “chemical pre-doping” approach for the rational shifting of the p–n junction for improved performance. Specifically, we demonstrate, by combined experiments and simulations, that the addition of a strong chemical reductant termed “reduced benzyl viologen” to a common active-material ink during LEC fabrication results in a filling of deep electron traps and an associated shifting of the emissive p–n junction from the center of the active material towards the positive anode. We finally demonstrate that this chemical pre-doping approach can improve the emission efficiency and stability of a common LEC device.

The combination of chemotherapy and photodynamic therapy (PDT) based on nanoparticles (NPs) has been extensively developed to improve the therapeutic effect and decrease the systemic toxicity of current treatments. However, overexpressed glutathione (GSH) in tumor cells efficiently scavenges singlet oxygens (1O2) generated from photosensitizers and results in the unsatisfactory efficacy of PDT. To address this obstacle, here we design H2O2-responsive polymer prodrug NPs with GSH-scavenger (Ce6@P(EG-a-CPBE) NPs) for chemo-photodynamic synergistic cancer therapy. They are constructed by the co-self-assembly of photosensitizer chlorin e6 (Ce6) and amphiphilic polymer prodrug P(EG-a-CPBE), which is synthesized from a hydrophilic alternating copolymer P(EG-a-PD) by conjugating hydrophobic anticancer drug chlorambucil (CB) via an H2O2-cleavable linker 4-(hydroxymethyl)phenylboronic acid (PBA). Ce6@P(EG-a-CPBE) NPs can efficiently prevent premature drug leakage in blood circulation because of the high stability of the PBA linker under the physiological environment and facilitate the delivery of Ce6 and CB to the tumor site after intravenous injection. Upon internalization of Ce6@P(EG-a-CPBE) NPs by tumor cells, PBA is cleaved rapidly triggered by endogenous H2O2 to release CB and Ce6. Ce6 can effectively generate abundant 1O2 under 660 nm light irradiation to synergistically kill cancer cells with CB. Concurrently, PBA can be transformed into a GSH-scavenger (quinine methide, QM) under intracellular H2O2 and prevent the depletion of 1O2, which induces the cooperatively strong oxidative stress and enhanced cancer cell apoptosis. Collectively, such H2O2-responsive polymer prodrug NPs loaded with photosensitizer provide a feasible approach to enhance chemo-photodynamic synergistic cancer treatment.

Mesenchymal stem cells (MSCs) have shown great potential for the treatment of liver injuries, and the therapeutic efficacy greatly depends on their homing to the site of injury. In the present study, we detected significant upregulation of hepatocyte growth factor (HGF) in the serum and liver in mice with acute or chronic liver injury. In vitro study revealed that upregulation of miR-9-5p or miR-221-3p promoted the migration of human MSCs (hMSCs) toward HGF. Moreover, overexpression of miR-9-5p or miR-221-3p promoted hMSC homing to the injured liver and resulted in significantly higher engraftment upon peripheral infusion. hMSCs reduced hepatic necrosis and inflammatory infiltration but showed little effect on extracellular matrix (ECM) deposition. By contrast, hMSCs overexpressing miR-9-5p or miR-221-3p resulted in not only less centrilobular necrosis and venous congestion but also a significant reduction of ECM deposition, leading to obvious improvement of hepatocyte morphology and alleviation of fibrosis around central vein and portal triads. Further studies showed that hMSCs inhibited the activation of hepatic stellate cells (HSCs) but could not decrease the expression of TIMP-1 upon acute injury and the expression of MCP-1 and TIMP-1 upon chronic injury, while hMSCs overexpressing miR-9-5p or miR-221-3p led to further inactivation of HSCs and downregulation of all three fibrogenic and proinflammatory factors TGF-β, MCP-1, and TIMP-1 upon both acute and chronic injuries. Overexpression of miR-9-5p or miR-221-3p significantly downregulated the expression of α-SMA and Col-1α1 in activated human hepatic stellate cell line LX-2, suggesting that miR-9-5p and miR-221-3p may partially contribute to the alleviation of liver injury by preventing HSC activation and collagen expression, shedding light on improving the therapeutic efficacy of hMSCs via microRNA modification.

Abstract The growth of wheat (Triticum aestivum) is constrained by soil salinity, although some fungal species have been shown to enhance production in saline environments. The yield of grain crops is affected by salt stress, and this study aimed to investigate how arbuscular mycorrhizal fungus (AMF) mitigates salt stress. An experiment was conducted to assess the impact of AMF on wheat growth and yield in conditions of 200 mM salt stress. Wheat seeds were coated with AMF at a rate of 0.1 g (108 spores) during sowing. The results of the experiment demonstrated that AMF inoculation led to a significant improvement in the growth attributes of wheat, including root and shoot length, fresh and dry weight of root and shoot. Furthermore, a significant increase in chlorophyll a, b, total, and carotenoids was observed in the S2 AMF treatment, validating the effectiveness of AMF in enhancing wheat growth under salt stress conditions. Additionally, AMF application reduced the negative effects of salinity stress by increasing the uptake of micronutrients such as Zn, Fe, Cu, and Mn while regulating the uptake of Na (decrease) and K (increase) under salinity stress. In conclusion, this study confirms that AMF is a successful strategy for reducing the negative effects of salt stress on wheat growth and yield. However, further investigations are recommended at the field level under different cereal crops to establish AMF as a more effective amendment for the alleviation of salinity stress in wheat.

Abstract Background Rosa rugosa is a shrub that originated in China and has economic and ecological value. However, during the development of R. rugosa, the genetic background was chaotic, and the genetic structure among different wild populations was unclear, as well as wild and cultivated accessions. Here, we report whole-genome resequencing of wild and cultivated R. rugosa accessions. Results A total of 19,041,284 SNPs were identified in 188 R. rugosa accessions and 3 R. chinensis accessions by resequencing. Population genetic analysis revealed that cultivated and wild groups were separated very early. All R. rugosa accessions were divided into 8 categories based on genetic structure: (1) Weihai, Yantai, and Liaoning category, (2) Jilin category, and (3) Hammonasset category (above three are wild); (4) traditional varieties, (5) hybrids between R. rugosa and R. chinensis, (6) Zizhi Rose, (7) Kushui Rose, (8) hybrids between R. rugosa and R. multiflora. We found that the heterozygosity and genetic diversity of wild accessions were generally lower than those of cultivated individuals. The genes that were selected during cultivation were identified, and it was found that these genes were mainly related to environmental adaptation and growth. Conclusions The Jilin population was the oldest population and later migrated to Liaoning and then migrated to Yantai and Weihai by sea regression in the Bohai Basin. The Hammonasset naturalized population probably originated from the Jilin population and then experienced separate differentiation. The long-term asexual reproduction pattern of R. rugosa decreased genetic diversity in the wild population. During R. rugosa cultivation, the ancestors of the Jilin population were involved in breeding traditional varieties, after which almost no wild individuals were engaged in breeding. However, in recent decades, cross breeding of R. rugosa started the utilization of wild germplasms. In comparison, some other species play important roles in variety formation. Few genes related to economic traits were selected, suggesting no directional domestication in the R. rugosa cultivation process.

Abstract Background Radiotherapy is an essential treatment for chest cancer. Radiation-induced pulmonary fibrosis (RIPF) is an almost irreversible interstitial lung disease; however, its pathogenesis remains unclear. Methods We analyzed specific changes in cell populations and potential markers by using single-cell sequencing datasets from the Sequence Read Archive database, PERFORMED from control (0 Gy) and thoracic irradiated (20 Gy) mouse lungs at day 150 post-radiation. We performed IHC and ELISA on lung tissue and cells to validate the potential marker cytokines identified by the analysis on rat thoracic irradiated molds (30 Gy). Results Single-cell sequencing analysis showed changes in abundance across cell types and at the single-cell level, with B and T cells showing the most significant changes in abundance. And four cytokines, CCL5, ICAM1, PF4, and TNF, were significantly upregulated in lung tissues of RIPF rats and cell supernatants after ionizing radiation. Conclusion Cytokines CCL5, ICAM1, PF4, and TNF may play essential roles in radiation pulmonary fibrosis. They are potential targets for the treatment of radiation pulmonary fibrosis.

Abstract The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies, counting the epitopes and genotypes of these antibodies. We further comprehensively analyzed the impact of Omicron mutations on antibody epitopes and classified these antibodies according to their binding patterns. We found that the epitopes of the H-RBD class antibodies were significantly less affected by Omicron mutations than other classes. Binding and virus neutralization experiments showed that such antibodies could effectively inhibit the immune escape of Omicron. Cryo-EM results showed that this class of antibodies utilized a conserved mechanism to neutralize SARS-CoV-2. Our results greatly help us deeply understand the impact of Omicron mutations. Meanwhile, it also provides guidance and insights for developing Omicron antibodies and vaccines.

Abstract The development of head and neck squamous cell carcinoma (HNSCC) is a multi-step process, and its survival depends on a complex tumor ecosystem, which not only promotes tumor growth but also helps to protect tumor cells from immune surveillance. With the advances of existing technologies and emerging models for ecosystem research, the evidence for cell-cell interplay is increasing. Herein, we discuss the recent advances in understanding the interaction between tumor cells, the major components of the HNSCC tumor ecosystem, and summarize the mechanisms of how biological and abiotic factors affect the tumor ecosystem. In addition, we review the emerging ecological treatment strategy for HNSCC based on existing studies.

The research investigated the potential of heterologous expression of the heat-shock protein PpHSP70 in enhancing high temperature and drought tolerance in rice. After screening the whole genome sequence of Physcomitrium patens in the Phytzome database, 30 members of the HSP70 gene family were obtained. Their expression and the tissue expression patterns under abiotic stressors of high temperature, drought, and salt were analyzed. During the four-leaf stage of rice, overexpressed materials were subjected to a temperature of 45 °C for 20 h and to drought conditions for one week. After processing, 5 overexpression PpHSP70 materials survived against high temperature, and 7 materials survived against drought, while all wild-type materials KY131 died after the treatment. The results demonstrated that overexpression of PpHSP70 significantly improved both high-temperature tolerance and drought. This study provides valuable insights into the utilization of heterologous expression for enhancing crop tolerance to abiotic stressors.

Sustainability discourses influence the practices of urban climate action by establishing objectives and ways of doing things. Key concepts such as ‘risk’, ‘resilience’ and ‘efficiency’ have been central in the history of sustainability discourses, but their influence has changed over time. The use of these terms is analysed in policy narratives of urban climate action, exploring how they are deployed in policy and practice. A document database (n = 463) was analysed to show how the terms have evolved from their application in specific contexts to a more open interpretation in which different forms of environmental action are linked to development. Interviews with practitioners (n = 100) were analysed to reveal the influence of these narratives and how they organise action in urban environments. Three tensions emerge from the mobilisations of hegemonic discourses in practice: the contradiction between facilitating harmonised approaches across locations while at the same time scaling up action; the contradiction between implementing action in place and providing frameworks of action that can be evaluated at the global scale; and the challenge between identifying sources of leadership and accepting the increasing importance of multiple actors in local climate action. These tensions open opportunities to disrupt climate change adaptation discourses. Policy relevance The history of the formation of environmental discourses has shaped climate policy at a fundamental level. These discourses contain embedded assumptions and reasoning that relate to their history and contextualisation rather than with absolute truths that inform them. Understanding the formation of these discourses may be necessary to identify the biases inherent to urban environmental practitioners’ discourses and to understand their effectiveness and operation. A better understanding of these discourses supports policymakers in shaping responses to environmental challenges and finding new narratives to inform sustainable futures. Improved knowledge has been created by focusing on the tensions that emerge from policy documents and practitioner interviews.

Cell death resistance is a hallmark of tumor cells that drives tumorigenesis and drug resistance. Targeting cell death resistance-related genes to sensitize tumor cells and decrease their cell death threshold has attracted attention as a potential antitumor therapeutic strategy. However, the underlying mechanism is not fully understood. Recent studies have reported that NeuroD1, first discovered as a neurodifferentiation factor, is upregulated in various tumor cells and plays a crucial role in tumorigenesis. However, its involvement in tumor cell death resistance remains unknown. Here, we found that NeuroD1 was highly expressed in hepatocellular carcinoma (HCC) cells and was associated with tumor cell death resistance. We revealed that NeuroD1 enhanced HCC cell resistance to ferroptosis, a type of cell death caused by aberrant redox homeostasis that induces lipid peroxide accumulation, leading to increased HCC cell viability. NeuroD1 binds to the promoter of glutathione peroxidase 4 (GPX4), a key reductant that suppresses ferroptosis by reducing lipid peroxide, and activates its transcriptional activity, resulting in decreased lipid peroxide and ferroptosis. Subsequently, we showed that NeuroD1/GPX4-mediated ferroptosis resistance was crucial for HCC cell tumorigenic potential. These findings not only identify NeuroD1 as a regulator of tumor cell ferroptosis resistance but also reveal a novel molecular mechanism underlying the oncogenic function of NeuroD1. Furthermore, our findings suggest the potential of targeting NeuroD1 in antitumor therapy.

Abstract Lanthanide (Ln3+) oxysulfide nanocrystals (NCs) have great prospect in many advanced technologies; however, they suffer from a low photoluminescence efficiency due to the volatility of sulfur and deleterious surface quenching effect. Herein, we report a novel sandwiched luminescent heterostructure based on Ln3+‐doped Gd2O2S@NaYF4 core/shell NCs with tunable sulfur content in the sandwich layer. By means of Eu3+ as the sensitive structural probes, we unravel the ligand‐mediated structure control of the NCs from Gd2O3: Ln3+@NaYF4 to Gd2O2S: Ln3+@NaYF4 with tailored S2– deficiency. Such a sandwich‐type core/shell heterostructure enables us to achieve efficient and multicolor downshifting and upconversion luminescence (UCL), with up to 208.8 folds of enhancement in UCL intensity as compared to that of their core‐only counterparts. These findings provide a general approach for the controlled synthesis of lanthanide oxysulfide@fluoride heterostructure, which offers a new way for the materials design towards diverse emerging applications.

ABSTRACTThe gut-joint axis, one of the mechanisms that mediates the onset and progression of joint and related diseases through gut microbiota, and shows the potential as therapeutic target. A variety of drugs exert therapeutic effects on rheumatoid arthritis (RA) through the gut-joint axis. However, the anti-inflammatory and immunomodulatory effect of novel photobiomodulatory therapy (PBMT) on RA need further validation and the involvement of gut-joint axis in this process remains unknown. The present study demonstrated the beneficial effects of PBMT on RA, where we found the restoration of gut microbiota homeostasis, and the related key pathways and metabolites after PBMT. We also discovered that the therapeutic effects of PBMT on RA mainly through the gut-joint axis, in which the amino acid metabolites (Alanine and N-acetyl aspartate) play the key role and rely on the activity of metabolic enzymes in the target organs. Together, the results prove that the metabolites of amino acid from gut microbiota mediate the regulation effect on the gut-joint axis and the therapeutic effect on rheumatoid arthritis of PBMT.

Diabetic kidney disease (DKD) is one of the severe complications of diabetes mellitus-related microvascular lesions, which remains the leading cause of end-stage kidney disease. The genesis and development of DKD is closely related to inflammation. Myeloid differentiation 2 (MD2) mediates hyperlyciemia-induced renal inflammation and DKD development and is considered as a potential therapeutic target of DKD. Here, we identified a new small-molecule MD2 inhibitor, JM-9. In vitro, JM-9 suppressed high glucose (HG) and palmitic acid (PA)-induced inflammation in MPMs, accompanied by inhibition of MD2 activation and the downstream TLR4/MyD88-MAPKs/NFκB pro-inflammatory signaling pathway. Macrophage-derived factors increased the fibrotic and inflammatory responses in renal tubular epithelial cells, which were inhibited by treating macrophages with JM-9. Then, we investigated the therapeutic effects against DKD in streptozotocin-induced type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) mouse models. Treatment with JM-9 prevented renal inflammation, fibrosis, and dysfunction by targeting MD2 in both T1DM and T2DM models. Our results show that JM-9, a new small-molecule MD2 inhibitor, protects against DKD by targeting MD2 and inhibiting MD2-mediated inflammation. In summary, JM-9 is a potential therapeutic agent for DKD.

Paraclostridium bifermentans (P.b) is an emerging human pathogen that is phylogenomically close to Paeniclostridium sordellii (P.s), while their populational genomic features and virulence capacity remain understudied. Here, we performed comparative genomic analyses of P.b and compared their pan-genomic features and virulence coding profiles to those of P.s. Our results revealed that P.b has a more plastic pangenome, a larger genome size, and a higher GC content than P.s. Interestingly, the P.b and P.s share similar core-genomic functions, but P.b encodes more functions in nutrient metabolism and energy conversion and fewer functions in host defense in their accessory-genomes. The P.b may initiate extracellular infection processes similar to those of P.s and Clostridium perfringens by encoding three toxin homologs (i.e., microbial collagenase, thiol-activated cytolysin, phospholipase C, which are involved in extracellular matrices degradation and membrane damaging) in their core-genomes. However, P.b is less toxic than the P.s by encoding fewer secretion toxins in the core-genome and fewer lethal toxins in the accessory-genome. Notably, P.b carries more toxins genes in their accessory-genomes, particularly those of plasmid origin. Moreover, three within-species and highly conserved plasmid groups, encoding virulence, gene acquisition, and adaptation, were carried by 25–33% of P.b strains and clustered by isolation source rather than geography. This study characterized the pan-genomic virulence features of P.b for the first time, and revealed that P. bifermentans is an emerging pathogen that can threaten human health in many aspects, emphasizing the importance of phenotypic and genomic characterizations of in situ clinical isolates.

The CRISPR/Cas9 system is a powerful genome editing tool that has made enormous impacts on next-generation molecular diagnostics and therapeutics, especially for genetic disorders that traditional therapies cannot cure. Currently, CRISPR-based gene editing is widely applied in basic, preclinical, and clinical studies. In this review, we attempt to identify trends in clinical studies involving CRISPR techniques to gain insights into the improvement and contribution of CRISPR/Cas technologies compared to traditional modified modalities. The review of clinical trials is focused on the applications of the CRISPR/Cas systems in the treatment of cancer, hematological, endocrine, and immune system diseases, as well as in diagnostics. The scientific basis underlined is analyzed. In addition, the challenges of CRISPR application in disease therapies and recent advances that expand and improve CRISPR applications in precision medicine are discussed.

Diseases pose a significant threat to the citrus industry, and the accurate detection of these diseases represent key factors for their early diagnosis and precise control. Existing diagnostic methods primarily rely on image models trained on vast datasets and limited their applicability due to singular backgrounds. To devise a more accurate, robust, and versatile model for citrus disease classification, this study focused on data diversity, knowledge assistance, and modal fusion. Leaves from healthy plants and plants infected with 10 prevalent diseases (citrus greening, citrus canker, anthracnose, scab, greasy spot, melanose, sooty mold, nitrogen deficiency, magnesium deficiency, and iron deficiency) were used as materials. Initially, three datasets with white, natural, and mixed backgrounds were constructed to analyze their effects on the training accuracy, test generalization ability, and classification balance. This diversification of data significantly improved the model’s adaptability to natural settings. Subsequently, by leveraging agricultural domain knowledge, a structured citrus disease features glossary was developed to enhance the efficiency of data preparation and the credibility of identification results. To address the underutilization of multimodal data in existing models, this study explored semantic embedding methods for disease images and structured descriptive texts. Convolutional networks with different depths (VGG16, ResNet50, MobileNetV2, and ShuffleNetV2) were used to extract the visual features of leaves. Concurrently, TextCNN and fastText were used to extract textual features and semantic relationships. By integrating the complementary nature of the image and text information, a joint learning model for citrus disease features was achieved. ShuffleNetV2 + TextCNN, the optimal multimodal model, achieved a classification accuracy of 98.33% on the mixed dataset, which represented improvements of 9.78% and 21.11% over the single-image and single-text models, respectively. This model also exhibited faster convergence, superior classification balance, and enhanced generalization capability, compared with the other methods. The image-text multimodal feature fusion network proposed in this study, which integrates text and image features with domain knowledge, can identify and classify citrus diseases in scenarios with limited samples and multiple background noise. The proposed model provides a more reliable decision-making basis for the precise application of biological and chemical control strategies for citrus production.

Background Glioma is one of the most malignant tumors, which leads to high mortality in cancer patients. At present, there is no effective therapy for glioma. Therefore, it is urgent and necessary to find new molecular targets for anti-glioma therapy. Objective The present study aimed to investigate the role of signal transducer and activator of transcription 1 (STAT1) in the development and progression of human glioma and related mechanisms. Methods According to the instructions of Lipofectamine TM 2000 transfection reagent, we transiently transfected the plasmid pcDNA3.1-STAT1 into glioma U251 cells. Then STAT1 expression in glioma U251 and LN382 cells was detected by Western blot. MTT was performed to assay the proliferative activity of U251 cells after STAT1 transduction, flow cytometry was used to detect cell cycle and apoptosis indicators, cell migration indicator was determined by Wound healing, and Western blot was used for detecting the expression level and change trend of p53, p21, bcl-2, Caspase-8, Cyclin A and Cyclin E in transfected cells. Results Overexpressed STAT1 significantly inhibited U251 cell proliferation and promoted U251 cell apoptosis. Meanwhile, high expression of STAT1 can increase the expression of p53, p21, and Caspase-8 while inhibiting the expression of bcl-2, Cyclin A, and Cyclin E. Conclusion Highly expressed STAT1 inhibits the proliferative activity of human glioma U251 cells and can promote tumor cell apoptosis and block cell cycle progression while regulating the expression of various signal transduction molecules. Thus, STAT1 has a critical function in the development and progression of glioma and is a novel target for glioma therapy.

Abstract Non-protein target drugs, especially RNA-based gene therapies for treating hereditary diseases, have been recognized worldwide. As cancer is an insurmountable challenge, no miracle drug is currently available. With the advancements in the field of biopharmaceuticals, research on cancer therapy has gradually focused on non-protein target-targeted drugs, especially RNA therapeutics, including oligonucleotide drugs and mRNA vaccines. This review mainly summarizes the clinical research progress in RNA therapeutics and highlights that appropriate target selection and optimized delivery vehicles are key factors in increasing the effectiveness of cancer treatment in vivo.

Abstract Renal cell carcinoma (RCC) is the second lethal urogenital malignancy with the increasing incidence and mortality in the world. Clear cell renal cell carcinoma (ccRCC) is one major subtype of RCC, which accounts for about 70 to 80% of all RCC cases. Although many innovative therapeutic options have emerged during the last few decades, the efficacy of these treatments for ccRCC patients is very limited. To date, the prognosis of patients with advanced or metastatic ccRCC is still poor. The 5-year survival rate of these patients remains less than 10%, which mainly attributes to the complexity and heterogeneity of the tumor microenvironment (TME). It has been demonstrated that long non-coding RNAs (lncRNAs) perform an indispensable role in the initiation and progression of various tumors. They mostly function as sponges for microRNAs (miRNAs) to regulate the expression of target genes, finally influence the growth, metastasis, apoptosis, drug resistance and TME of tumor cells. However, the role of lncRNA/miRNA/mRNA axis in the TME of ccRCC remains poorly understood. In this review, we summarized the biological function of lncRNA/miRNA/mRNA axis in the pathogenesis of ccRCC, then discussed how lncRNA/miRNA/mRNA axis regulate the TME, finally highlighted their potential application as novel biomarkers and therapeutic targets for ccRCC.

AimsCircular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.MethodsMinus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.ResultsTensile strain could decrease the expression of circStrn3 in chondrocytes. CircStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively ‘sponging’ miRNA-9-5p targeting Kruppel-like factor 5 (KLF5), indicating that the decrease in circStrn3 might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblast differentiation by targeting KLF5. Intra-articular injection of exosomal miR-9-5p alleviated the progression of OA induced by destabilized medial meniscus surgery in mice.ConclusionTaken together, these results demonstrate that reduction of circStrn3 causes an increase in miR-9-5p, which acts as a protective factor in mechanical instability-induced OA, and provides a novel mechanism of communication among joint components and a potential application for the treatment of OA.Cite this article: Bone Joint Res 2023;12(1):33–45.

The English grain aphid (EGA) (Sitobion avenae F.) is one of the most destructive species of aphids in wheat- (Triticum aestivum L.) planting areas worldwide. Large quantities of insecticides are usually used to control aphid damage. The identification of new EGA-resistant genes is necessary for sustainable wheat production. The objective of this study was to identify candidate genes for EGA resistance from stable quantitative trait loci (QTLs). We previously constructed a genetic map of unigenes (UG-Map) with 31,445 polymorphic sub-unigenes via the RNA sequencing of ‘TN18 × LM6’ recombinant inbred lines (TL-RILs). The relative aphid index (RAI) for the TL-RILs was investigated for two growing seasons, with three measured times (MTs) in each season. Using the UG-Map, 43 candidate genes were identified from 22 stable QTLs, with an average of 1.95 candidate genes per QTL. Among the 34 candidate genes annotated in the reference genome Chinese Spring (CS) RefSeq v1.1, the homologous genes of seven candidate genes, TraesCS1A02G-319900, TraesCS1B02G397300, TraesCS2D02G460800, TraesCS4A02G015600LC, TraesCS5B02G329200, TraesCS-6A02G000600 and TraesCS6A02G418600LC have been previously reported to play roles in aphid resistance. This suggests that these genes are strongly associated with EGA resistance in wheat. The candidate genes in this study should facilitate the cloning of EGA-resistant genes and genetic improvement in wheat breeding programs.

Drought-induced metabolic dysregulation significantly enhances the production of reactive oxygen species (ROS), which, in turn, exerts a substantial influence on the oxidation–reduction regulatory status of cells. These ROS, under conditions of drought stress, become highly reactive entities capable of targeting various plant organelles, metabolites, and molecules. Consequently, disruption affects a wide array of metabolic pathways and eventually leads to the demise of the cells. Given this understanding, this study aimed to investigate the effects of different drought stress levels on the growth and development of the invasive weed Wedelia trilobata and its co-responding native counterpart Wedelia chinensis. Both plants evolved their defense mechanisms to increase their antioxidants and hormone contents to detoxify ROS to avoid oxidative damage. Still, the chlorophyll content fluctuated and increased in a polyethylene-glycol-simulated drought. The proline content also rose in the plants, but W. chinensis showed a significant negative correlation between proline and malondialdehyde in different plant parts. Thus, W. trilobata and W. chinensis exhibited diverse or unlike endogenous hormone regulation patterns under drought conditions. Meanwhile, W. trilobata and W. chinensis pointedly increased the content of indole acetic acid and gibberellic acid in a different drought stress environment. A positive correlation was found between endogenous hormones in other plant parts, including in the roots and leaves. Both simulated and natural drought conditions exerted a significant influence on both plant species, with W. trilobata displaying superior adaptation characterized by enhanced growth, bolstered antioxidant defense mechanisms, and heightened hormonal activities.

Airborne speech enhancement is always a major challenge for the security of airborne systems. Recently, multi-objective learning technology has become one of the mainstream methods of monaural speech enhancement. In this paper, we propose a novel multi-objective method for airborne speech enhancement, called the stacked multiscale densely connected temporal convolutional attention network (SMDTANet). More specifically, the core of SMDTANet includes three parts, namely a stacked multiscale feature extractor, a triple-attention-based temporal convolutional neural network (TA-TCNN), and a densely connected prediction module. The stacked multiscale feature extractor is leveraged to capture comprehensive feature information from noisy log-power spectra (LPS) inputs. Then, the TA-TCNN adopts a combination of these multiscale features and noisy amplitude modulation spectrogram (AMS) features as inputs to improve its powerful temporal modeling capability. In TA-TCNN, we integrate the advantages of channel attention, spatial attention, and T-F attention to design a novel triple-attention module, which can guide the network to suppress irrelevant information and emphasize informative features of different views. The densely connected prediction module is used to reliably control the flow of the information to provide an accurate estimation of clean LPS and the ideal ratio mask (IRM). Moreover, a new joint-weighted (JW) loss function is constructed to further improve the performance without adding to the model complexity. Extensive experiments on real-world airborne conditions show that our SMDTANet can obtain an on-par or better performance compared to other reference methods in terms of all the objective metrics of speech quality and intelligibility.

Dalbergia cultrata Pierre Graham ex Benth (D. cultrata) is a precious rosewood tree species that grows in the tropical and subtropical regions of Asia. In this study, we used PacBio long-reading sequencing technology and Hi-C assistance to sequence and assemble the reference genome of D. cultrata. We generated 171.47 Gb PacBio long reads and 72.43 Gb Hi-C data and yielded an assembly of 10 pseudochromosomes with a total size of 690.99 Mb and Scaffold N50 of 65.76 Mb. The analysis of specific genes revealed that the triterpenoids represented by lupeol may play an important role in D. cultrata’s potential medicinal value. Using the new reference genome, we analyzed the resequencing of 19 Dalbergia accessions and found that D. cultrata and D. cochinchinensis have the latest genetic relationship. Transcriptome sequencing of D. cultrata leaves grown under cold stress revealed that MYB transcription factor and E3 ubiquitin ligase may be playing an important role in the cold response of D. cultrata. Genome resources and identified genetic variation, especially those genes related to the biosynthesis of phytochemicals and cold stress response, will be helpful for the introduction, domestication, utilization, and further breeding of Dalbergia species.

Aegilops tauschii (Coss.) is a highly deleterious, rapidly proliferating weed within the wheat, and its DD genome composition exhibits adaptability toward diverse abiotic stresses and demonstrates heightened efficacy in nutrient utilization. Current study investigated different variegated impacts of distinct nitrogen concentrations with varied plant densities, scrutinizing the behavior of Ae. tauschii under various salinity and drought stress levels through multiple physiological, biochemical, and molecular pathways. Different physiological parameters attaining high growth with different plant density and different nitrogen availability levels increased Ae. tauschii dominancy. Conversely, under the duress of salinity and drought, Ae. tauschii showcased an enhanced performance through a comprehensive array of physiological and biochemical parameters, including catalase, peroxidase, malondialdehyde, and proline content. Notably, salinity-associated traits such as sodium, potassium, and the sodium–potassium ratio exhibited significant variations and demonstrated remarkable tolerance capabilities. In the domain of molecular pathways, the HKT and DREB genes have displayed a remarkable upregulation, showcasing a comparatively elevated expression profile in reaction to different levels of salinity and drought-induced stress. Without a doubt, this information will make a substantial contribution to the understanding of the fundamental behavioral tendencies and the efficiency of nutrient utilization in Ae. tauschii. Moreover, it will offer innovative viewpoints for integrated management, thereby enabling the enhancement of strategies for adept control and alleviation.

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly pathogenic to humans and has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic. Vaccines are one of the efficient ways to prevent the viral infection. After COVID-19 vaccination, the monitoring of the dynamic change in neutralizing antibodies is necessary to determine booster requirements.MethodsWe estimated the effectiveness of the inactivated vaccines by monitoring dynamic SARS-CoV-2 neutralizing antibodies for over 2 years. Additionally, we also investigated the activation of T lymphocytes (CD3+ T cells) after three doses of the inactivated vaccine.ResultThe results showed that the rate of reduction of SARS-CoV-2 neutralizing antibody levels gradually showed after each booster dose. The IgG/IgM level at 9 months after the third vaccination were significantly higher than those at 6 months after the second dose (p

ABSTRACT: Introduction and Objectives: Hepatocellular carcinoma (HCC) may be diagnosed using the GAAP and ASAP models; our goal was to verify and evaluate their diagnostic effectiveness compared to alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and AFP & DCP for both HCC and HCC caused by the hepatitis B virus (HBV). Patients and Methods: GAAP and ASAP models were validated and compared using a retrospective investigation of 938 patients from our hospital between July 2020 and July 2021. Results: Both the GAAP and ASAP models had better diagnostic efficacy than AFP, DCP, AFP & DCP. The GAAP model achieved better performance in section A for the detection of HCC and in section C for the detection of HBV-HCC than the ASAP model. The Hosmer-Lemeshow test showed that the GAAP and ASAP models were well-calibrated for the diagnoses of these two groups. To be more specific, the area under curve (AUC) of the GAAP model for HCC detection in section A was 0.862 [95% confidence interval (CI): 0.838-0.883], and that of the ASAP model was 0.850 [95% CI: 0.826-0.872]. The AUC of the GAAP model for HBV-HCC detection in section C was 0.897 [95% CI: 0.872-0.918], and that of the ASAP model was 0.878 [95% CI: 0.852-0.902]. Conclusions: The GAAP model was more accurate and reliable than the AFP, DCP, AFP and DCP, as well as the ASAP model in section A for the detection of HCC and in section C for the detection of HBV-HCC.

Abstract Background In mice, liver fibrosis is the most serious pathologic change during Schistosoma japonicum (S. japonicum) infection. Schistosomiasis is mainly characterized by schistosome egg-induced granulomatous fibrosis. Hepatic stellate cells (HSCs) are mainly responsible for the net accumulation of collagens and fibrosis formation in the liver. Activated HSCs regulated by transforming growth factor-β1 (TGF-β1)/Smad signaling have emerged as the critical regulatory pathway in hepatitis virus or carbon tetrachloride-induced liver fibrosis. However, the detailed mechanism of HSC activation in schistosome-induced liver fibrosis is poorly understood. Methods Schistosoma japonicum-induced murine models and a control group were generated by abdominal infection with 15 (± 1) cercariae. The purity of cultured primary HSCs was evaluated by immunocytochemistry. The histopathological changes in the livers of infected mice were estimated by hematoxylin–eosin and Masson staining. Dynamic expression of pro-fibrotic molecules and microRNAs was detected by real-time quantitative PCR (RT-qPCR). Mainly members involved in the TGF-β1/Smad signaling pathway were examined via RT-qPCR and Western blot. Results The egg-induced granulomatous inflammation formed at 4 weeks post-infection (wpi) and developed progressively. Alpha-smooth muscle actin (α-SMA), collagen I, collagen III, TGF-β1, Smad2, Smad3, and Smad4 showed a significant increase in mitochondrial RNA (mRNA) and protein expression compared with the control group at 7 and 9 weeks post-infection (wpi), while an opposite effect on Smad7 was observed. In addition, the mRNA expression of microRNA-21 (miRNA-21) was significantly increased at 7 wpi, and the mRNA expression of miRNA-454 was decreased starting from 4 wpi. Conclusion Our present findings revealed that HSCs regulated by the TGF-β1/Smad signaling pathway play an important role in liver fibrosis in S. japonicum-infected mice, which may provide proof of concept for liver fibrosis in schistosomiasis. Graphical Abstract

Abstract Appropriate overtaking can improve the safety and efficiency of driving. Practically, overtaking consists of two asymmetric lane‐changes: firstly to the left lane and then return back. Existing literatures treated the two lane‐changes as the same behaviour, which may result in frequent and unnecessary lane‐changes. For the more complex first lane‐change, discretionary lane‐change strategies have been developed to gain speed advantage with least deceleration. Most of them, however, described vehicles' dynamics with rough simplifications different from actual execution (e.g. constant speed and constant acceleration), which may fail them in practical applications. This paper presents an event‐triggered overtaking decision‐making strategy for autonomous vehicles to make the overtaking meet the driver's expectations. Firstly, the difference between the left‐lane change and right‐lane change is analysed. Left‐lane change is mainly concerned with the efficiency, whereas driving safety is the main target of the right‐lane change. Secondly, an event‐triggering condition covering the speed difference between the ego vehicle and its preceding vehicle is set. Afterwards, based on quantified speed advantage, considering surrounding vehicles' changes in both speed and acceleration, an optimisation of overtaking decision‐making strategy is proposed. During right‐lane change in an overtaking, safety is ensured by predicting whether the ego vehicle will collide with surrounding vehicles. Finally, several scenarios are defined in the combination of SCANeR studio and Simulink, which are used to test and demonstrate the effectiveness and applicability of the overtaking decision‐making strategy. The results show that the proposed overtaking decision‐making strategy, by mathematical quantification of speed advantage, performs well in measuring the motivation of lane‐change and avoiding frequent lane changes, which correspond to driver habits.

Abstract Background Aberrant cytokeratin 7 expression by hepatocytes (CK7+Hs) is the hallmark characteristic of cholestasis diseases, especially in ductopenia diseases such as primary biliary cholangitis (PBC). This study attempted to evaluate the differences and relationships between the clinical and histological features of aberrant cytokeratin 7 (CK7) expression by hepatocytes in PBC patients. Methods The clinicopathological data of patients diagnosed with PBC at the Second Hospital of Nanjing between January 2016 and September 2018 were analysed with SPSS 20.0. Results Eighty-nine PBC patients who underwent liver biopsy were enrolled in this study, and 15, 29 and 45 patients had aberrant CK7 expression by hepatocytes (CK7+Hs (2 +), CK7+Hs (1 +), and CK7−Hs, respectively). There were significant differences in TB, DB, ALP, TA, IgM, interface activity, and ductopenia grade between patients with CK7−Hs and CK7+Hs (2 +) (P

In order to improve the comprehensive utilization rate of V2O5 form vanadium titanomagnetite concentrates, the direct leaching and the roasting-leaching tests were carried out using titanium white waste acid byorthogonal experiment method. The results of direct leaching experiment show that the liquid-solid ratio is the most important factor affecting the leaching rate of V2O5, and the concentration of titanium white waste acid is the least. The 71.05% vanadium can be leached under the experimental condition of 20% of titanium white waste acid, 90℃ for 90 min with a liquid-to-solid ratio of 5. The results of roasting-leaching experiment show that the effects of roasting temperature, K2CO3 ratio, Na2CO3 ratio and roasting time on the leaching rate of V2O5 are from large to small. When the conditions of roasting time of 2 h, roasting temperature of 1000℃, Na2CO3 ratio of 10%, and K2CO3 ratio of 10%, and the leaching rate of V2O5 can reach 84.48%.

Abstract Anaplastic thyroid carcinoma (ATC) is an extremely malignant type of endocrine cancer frequently accompanied by extrathyroidal extension or metastasis through mechanisms that remain elusive. We screened for the CREB3 transcription-factor family in a large cohort, consisting of four microarray datasets. This revealed that CREB3L1 was specifically up regulated in ATC tissues and negatively associated with overall survival of patients with thyroid cancer. Consistently, high expression of CREB3L1 was negatively correlated with progression-free survival in an independent cohort. CREB3L1 knockdown dramatically attenuated invasion of ATC cells, whereas overexpression of CREB3L1 facilitated the invasion of papillary thyroid carcinoma (PTC) cells. Loss of CREB3L1 inhibited metastasis and tumor growth of ATC xenografts in zebrafish and nude mouse model. Single-cell RNA-sequencing analysis revealed that CREB3L1 expression gradually increased during the neoplastic progression of a thyroid follicular epithelial cell to an ATC cell, accompanied by the activation of the extracellular matrix (ECM) signaling. CREB3L1 knockdown significantly decreased the expression of collagen subtypes in ATC cells and the fibrillar collagen in xenografts. Due to the loss of CREB3L1, ATC cells were unable to activate alpha-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs). After CREB3L1 knockdown, the presence of CAFs inhibited the growth of ATC spheroids and the metastasis of ATC cells. Further cytokine array screening showed that ATC cells activated α-SMA-positive CAFs through CREB3L1-mediated IL-1α production. Moreover, KPNA2 mediated the nuclear translocation of CREB3L1, thus allowing it to activate downstream ECM signaling. These results demonstrate that CREB3L1 maintains the CAF-like property of ATC cells by activating the ECM signaling, which remodels the tumor stromal microenvironment and drives the malignancy of ATC. Graphical Abstract

Fish viscera are one of the main by-products of fish processing, and often considered a low value resource, so they are mostly discarded. Fish viscera contain high levels of protein, and fish protein hydrolysates (FPH) have functional activities such as antioxidant, hypoglycemic, anti-inflammatory, and blood pressure reduction, and can be used as a potential functional ingredient and food additive. This paper reviews the research status of the preparation process and physiological activity of the hydrolysates of fish viscera protein in order to provide reference for the deep processing and utilization of fish viscera.