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The current popular traffic classification methods based on feature engineering and machine learning are difficult to obtain suitable traffic feature sets for multiple traffic classification tasks. Besides, data privacy policies prohibit network operators from collecting and sharing traffic data that might compromise user privacy. To address these challenges, we propose FedETC, a federated learning framework that allows multiple participants to learn global traffic classifiers, while keeping locally encrypted traffic invisible to other participants. In addition, FedETC adopts one-dimensional convolutional neural network as the base model, which avoids manual traffic feature design. In the experiments, we evaluate the FedETC framework for the tasks of both application identification and traffic characterization in a publicly available real-world dataset. The results show that FedETC can achieve promising accuracy rates that are close to centralized learning schemes.

To understand the stability of deep underground engineering rocks at high temperatures, it is necessary to conduct comprehensive tests on the mechanical properties of the rocks. In this study, a series of true triaxial tests (TTT) were conducted on sandstones using a self-developed true triaxial testing system combined with XRD, FE-SEM and CT analyses. The study systematically examined the microstructural characteristics, physical phase behavior, deformation properties and internal fracture development of the sandstone before and after heat treatment. The results of the study show that sandstone has temperature-dependent true triaxial mechanical properties after heat treatment. The stress-strain characteristic curves of the post-peak portion from room temperature to 800 °C show a significant stress-reducing segment, indicating the presence of brittle behavior. In addition, when the temperature exceeds 1000 °C, the sandstone exhibits brittle-ductile change characteristics, with a peak stress threshold observed at 800 °C. Notably, the peak stresses corresponding to 800 °C increased by 84.5 %, 63.1 %, 47 %, and 49.8 %, respectively, compared with the room temperature intermediate principal stresses(IPS) ranging from 20 MPa to 50 MPa, respectively. Importantly, the linear Mogi-Coulomb criterion remains valid for the peak strength of the high-temperature sandstone, while the internal fracture damage pattern of the specimens shows an inverted ''Y'' or inverted ''W'' configuration. The internal fracture network of rock samples above 800 °C is more complex. Intergranular crack is the main form of microcracking. This experimental study on the mechanical properties of sandstone under the combined effects of high temperature and real triaxial stresses provides valuable guidance for the selection of sandstone parameters and safety evaluation of coal underground gasification roofs.

Summary: Background: Type 2 diabetes (T2DM) remains a challenge to treat despite the expansion of various therapeutic classes. Visepegenatide (PB-119) is a once a week, subcutaneous, glucagon-like peptide-1 receptor agonist (GLP-1 RA) injection without the requirement of dose titration that has shown glycaemic control and safety profile in two phase 2 studies conducted in China and the United States, respectively. The aim of this study was to evaluate the efficacy and safety of visepegenatide as a monotherapy in treatment-naïve patients with T2DM. Methods: This was a multicentre, double-blind, parallel, placebo-controlled, phase 3 trial conducted in 30 centres in China. Adult participants (aged 18–75 years) with T2DM, glycated haemoglobin (HbA1c) of 7.5%–11.0% [58.47–96.73 mmol/mol], body mass index (BMI) of 18–40 kg/m2, and who had been treated with diet and exercise alone for at least 8 weeks before the screening visit were eligible for enrolment. After a 4-week placebo injection run-in period, participants with HbA1c of 7.0%–10.5% [53.0–91.3 mmol/mol] and fasting plasma glucose (FPG)

Summary: Hydrodesulfurization (HDS) is a commonly used route for producing clean fuels in modern refinery. Herein, ammonium/amine-intercalated MoS2 catalysts with various content of 1T phase and S vacancies have been successfully synthesized. Along with the increment of 1T phase and S vacancies of MoS2, the initial reaction rate of the HDS of dibenzothiophene (DBT) can be improved from 0.09 to 0.55 μmol·gcat−1·s−1, accounting for a remarkable activity compared to the-state-of-the-art catalysts. In a combinatory study via the activity evaluation and catalysts characterization, we found that the intercalation species of MoS2 played a key role in generating more 1T phase and S vacancies through the ‘intercalation-deintercalation’ processes, and the hydrogenation and desulfurization of HDS can be significantly promoted by 1T phase and S vacancies on MoS2, respectively. This study provides a practically meaningful guidance for developing more advanced HDS catalysts by the intercalated MoS2-derived materials with an in-depth understanding of structure-function relationships.

Because of its enhanced antitumor efficacy, lapatinib (LAP) is commonly used clinically in combination with the anthracycline drug doxorubicin (DOX) to treat metastatic breast cancer. While it is well recognized that this combination chemotherapy can lead to an increased risk of cardiotoxicity in adult women, its potential cardiotoxicity in the fetus during pregnancy remains understudied. Here, we aimed to examine the combination of LAP chemotherapy and DOX-induced cardiotoxicity in the fetus using a zebrafish embryonic system and investigate the underlying pathologic mechanisms. First, we examined the dose-dependent cardiotoxicity of combined LAP and DOX exposure in zebrafish embryos, which mostly manifested as pericardial edema, bradycardia, cardiac function decline and reduced survival. Second, we revealed that a significant increase in oxidative stress concurrent with activated MAPK signaling, as indicated by increased protein expression of phosphorylated p38 and Jnk, was a notable pathophysiological event after combined LAP and DOX exposure. Third, we showed that inhibiting MAPK signaling by pharmacological treatment with the p38MAPK inhibitor SB203580 or genetic ablation of the map2k6 gene could significantly alleviate combined LAP and DOX exposure-induced cardiotoxicity. Thus, we provided both pharmacologic and genetic evidence to suggest that inhibiting MAPK signaling could exert cardioprotective effects. These findings have implications for understanding the potential cardiotoxicity induced by LAP and DOX combinational chemotherapy in the fetus during pregnancy, which could be leveraged for the development of new therapeutic strategies.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

The solute carrier family 12 (SLC12) of cation-chloride cotransporters (CCCs) comprises potassium chloride cotransporters (KCCs, e.g. KCC1, KCC2, KCC3, and KCC4)-mediated Cl− extrusion, and sodium potassium chloride cotransporters (N[K]CCs, NKCC1, NKCC2, and NCC)-mediated Cl− loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues. In recent years, there have been considerable advances in our understanding of CCCs' control mechanisms in cell volume regulations, with many techniques developed in studying the functions and activities of CCCs. Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs. These techniques include the ammonium pulse technique, radioactive or nonradioactive rubidium ion uptake-assay, and thallium ion-uptake assay. CCCs' activity can also be indirectly observed by measuring γ-aminobutyric acid (GABA) activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes, radiotracer 36Cl−, and fluorescent dyes. Other techniques include directly looking at kinase regulatory sites phosphorylation, flame photometry, 22Na+ uptake assay, structural biology, molecular modeling, and high-throughput drug screening. This review summarizes the role of CCCs in genetic disorders and cell volume regulation, current methods applied in studying CCCs biology, and compounds developed that directly or indirectly target the CCCs for disease treatments.

Objective: To explore the correlation between hepatocellular carcinoma (HCC) gene variation profile and clinical characteristics in Han nationality with HBV infection in Sichuan province. Methods: The clinical data and HCC tissues were obtained from the enrolled patients. Whole exome sequencing and bioinformatics analysis were performed on formalin-fixed and paraffin-embedded samples from HCC. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Results: Sixteen high-frequency mutated genes with differential expressions were identified by WES. SMG1 gene variation could be positively correlated with satellite lesions. AMY2B and RGPD4 gene mutation seemed to have a greater chance of vascular invasion. The patients with TATDN1 variation have bigger diameters and greater chances of vascular and microvascular invasion (all P

The purpose of this study was to explore the protective effect of SeMet on renal injury induced by AFB1 in rabbits and its molecular mechanism. Forty rabbits of 35 days old were randomly divided into control group, AFB1 group (0.3 mg AFB1/kg b.w), 0.2 mg/kg Se + AFB1 group (0.3 mg AFB1/kg b.w + 0.2 mg SeMet/kg feed) and 0.4 mg/kg Se + AFB1 group (0.3 mg AFB1/kg b.w + 0.4 mg SeMet/kg feed). The SeMet treatment group was fed different doses of SeMet diets every day for 21 days. On the 17–21 day, the AFB1 treatment group, the 0.2 mg/kg Se + AFB1 group and the 0.4 mg/kg Se + AFB1 group were administered 0.3 mg AFB1 /kg b.w by gavage (dissolved in 0.5 ml olive oil) respectively. The results showed that AFB1 poisoning resulted in the changes of renal structure, the increase of renal coefficient and serum biochemical indexes, the ascent of ROS and MDA levels, the descent of antioxidant enzyme activity, and the significant down-regulation of Nrf2, HO-1 and NQO1. Besides, AFB1 poisoning increased the number of renal apoptotic cells, rised the levels of PTEN, Bax, Caspase-3 and Caspase-9, and decreased the levels of PI3K, AKT, p-AKT and Bcl-2. In summary, SeMet was added to alleviate the oxidative stress injury and apoptosis of kidney induced by AFB1, and the effect of 0.2 mg/kg Se + AFB1 is better than 0.4 mg/kg Se + AFB1.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the “structure” indicators have the highest proportion (80.00%) of high ranking and the “outcome” indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

Summary: Cancer cells usually exhibit shortened 3′ untranslated regions (UTRs) due to alternative polyadenylation (APA) to promote cell proliferation and migration. Upregulated CPSF6 leads to a systematic prolongation of 3′ UTRs, but CPSF6 expression in tumors is typically higher than that in healthy tissues. This contradictory observation suggests that it is necessary to investigate the underlying mechanism by which CPSF6 regulates APA switching in cancer. Here, we find that CPSF6 can undergo liquid-liquid phase separation (LLPS), and elevated LLPS is associated with the preferential usage of the distal poly(A) sites. CLK2, a kinase upregulated in cancer cells, destructs CPSF6 LLPS by phosphorylating its arginine/serine-like domain. The reduction of CPSF6 LLPS can lead to a shortened 3′ UTR of cell-cycle-related genes and accelerate cell proliferation. These results suggest that CPSF6 LLPS, rather than its expression level, may be responsible for APA regulation in cancer cells.

In recent years, the incidence and mortality rate of cancer is raising worldwide. Traditional approaches for cancer patient management including surgery, chemotherapy, radiotherapy, and targeted therapies provide unsatisfactory results and are often associated with adverse reactions. Over the last few decades, nanotechnology has been a rapidly emerging area of theragnostic in clinical research. It plays a vital role as a bridge between the science and technology of miscellaneous nanoparticles (NPs) and nanomedicine. In general, NPs with a range of sizes of 1–100 nm are thought to be acceptable for cancer medications. NPs may enhance the consistency and solubility of therapeutic drugs to obtain site-specific targeting, controlled release, and safe for healthy organs. NPs have the benefit of pathophysiological properties, enhanced permeability and retention (EPR) effects, and an advantage in cancer targeting. Furthermore, theranostic nanoparticles have been established having incorporated diagnostics and therapy in a single system that might provide more personalized treatment with optimal doses and monitoring the distribution, targeting, and response to therapy by using imaging tools. In this review, we have discussed the classes of nanoparticles, targeting approaches, and implications of NPs for cancer theranostics with recent examples.

Thymopentin (TP5), a clinically used immunomodulatory pentapeptide, can efficiently promote thymocyte differentiation and influence mature T-cell function, thus playing an essential role in the cancer immunotherapy. However, the excellent water solubility and high IC50 of TP5 result in an uncontrolled release behavior, requiring a high loading efficiency to achieve high dosage. Here in, we reported that TP5, combined with specific chemotherapeutic agents, can co-assemble into nanogels due to multiple hydrogen bonding sites. The co-assembly of TP5 with chemotherapeutic agent doxorubicin (DOX) into a carrier-free and injectable chemo-immunotherapy nanogel can enhance the cancer immunity cycle against melanoma metastasis. In this study, the designed nanogel guarantees high drug loading of TP5 and DOX and ensures a site-specific and controlled release of TP5 and DOX with minimal side effects, thus addressing the bottlenecks encountered by current chemo-immunotherapy. Moreover, the released DOX can effectively induce tumor cell apoptosis and immunogenic cell death (ICD) to activate immune initiation. Meanwhile, TP5 can significantly promote the proliferation and differentiation of dendritic cells (DCs) and T lymphocytes to amplify the cancer immunity cycle. As a result, this nanogel shows excellent immunotherapeutic efficacy against melanoma metastasis, as well as an effective strategy for TP5 and DOX application.

N6-methyladenosine (m6A) is a ubiquitous mRNA modification in eukaryotes. m6A occurs through the action of methyltransferases, demethylases, and methylation-binding proteins. m6A methylation of RNA is associated with various neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), depression, cerebral apoplexy, brain injury, epilepsy, cerebral arteriovenous malformations, and glioma. Furthermore, recent studies report that m6A-related drugs have attracted considerable concerns in the therapeutic areas of neurological disorders. Here, we mainly summarized the role of m6A modification in neurological diseases and the therapeutic potential of m6A-related drugs. The aim of this review is expected to be useful to systematically assess m6A as a new potential biomarker and develop innovative modulators of m6A for the amelioration and treatment of neurological disorders.

Iron widely exists in minerals and food, and has an essential role in human health. A major iron-regulating peptide hormone, hepcidin, maintains the balance of iron metabolism. The association between serum iron, hepcidin levels, and stroke risk is still under ongoing research. In this meta-analysis, Random‐effects meta‐analysis revealed that stroke patients had significantly higher serum iron and hepcidin levels compared with HC subjects. Further analysis of serum hepcidin levels in different degrees of stroke and its relation to prognosis revealed that hepcidin level is also associated with the degrees and prognosis of stroke. Finally, the role of iron overload in the mechanism of stroke development and the effect and mechanism of iron chelator intervention in stroke were also reviewed. Overall, the findings indicate that stroke patients had higher serum iron and hepcidin levels compared with healthy subjects, and their changes were associated with the severity and prognosis of stroke.

Mycoplankton play a key role in aquatic microbial food webs and nutrient cycling. However, the environmental factors that affect their composition and trophic modes in coastal water remain unclear. In this study, we used fungal metabarcoding to characterize seasonal mycoplanktonic communities in the surface water of the Maowei Sea. Dothideomycetes and Sordariomycetes were the dominant classes in the Maowei Sea. Random forest modeling analyses suggested that Ochroconis, Rhodotorula, Perenniporia and Derxomyces were the best seasonal bioindicators of environmental changes. Spearman’s correlation analysis showed that TOC (total organic carbon) is the main factor affecting mycoplanktonic bioindicators. Through FUNGuild analysis, we classified mycoplankton in the Maowei Sea into eight trophic modes and found that saprotrophs were the most abundant. Random forest analysis and Spearman’s correlation indicated that the mycoplankton trophic modes could reflect environmental changes in the Maowei Sea and were mainly influenced by dissolved inorganic phosphorus (DIP), dissolved oxygen (DO), and total organic carbon (TOC). Mycoplanktonic alpha and beta diversities significantly varied in different seasons (p

Purpose: Microglia-neuron crosstalk is critically involved in synaptic plasticity and degeneration by releasing diverse mediators in Alzheimer’s disease (AD). Therefore, determining contributors that modulate the systemic microenvironment is essential. Cordycepin (CCS) is a novel neuroprotective compound obtained from Cordyceps militaris. However, the anti-AD efficacy and potential mechanism of CCS treatment remain unclear. This study aimed to elucidate the microglia-neuron symphony in AD after CCS treatment and to explore the possible mechanisms of its neuroprotective efficacy. Methods and results: CCS treatment improved learning and memory impairment in 9-month-old APP/PS1 mice by behavioral tests. CCS polarized the microglia from M1 to M2, inhibited neuronal apoptosis and promoted synaptic remodeling accompanied by in vivo and in vitro upregulation of NGF. The cAMP-response element-binding protein (CREB) was also activated after MG-M2 polarization. Further, we verified that the sg3 promoter region of NGF (–1018 to –1011) is the key binding site for CREB-induced NGF transcription, which increased NGF expression and secretion. Finally, microglia-derived NGF was confirmed as an important mediator in microglia-neuron symphony to improve the neuronal microenvironment after CCS treatment. Conclusions: CCS improved the neuronal synaptic plasticity and senescence by promoting MG-M2 activation driven by CREB-induced NGF upregulation and facilitated symphony communication between the microglia and neuron in AD. This study provides a new perspective on the development of a novel strategy for anti-AD therapy and offers new targets for anti-AD drug development.

In general, modified starches provided a desirable feature so that they can be used in the food industry like food additive products. The awareness of eating healthy has become very evident. The food industry is willing to produce foods and food ingredients that not only maintain nutrition but also promote health and safety. Tartary buckwheat starch has been isolated to assess the effect of HMT on its digestibility, morphological structure, pasting, thermal and textural properties and compared with common buckwheat, sorghum, and broomcorn millet. HMT changed significantly the granular structure of native starches. The complete starch granular structure increased the size and changed into an irregular shape, with a rough surface. The modified starches exhibited higher onset and peak temperatures, while their amylose content, solubility, swelling power, gel hardness, and enthalpy of gelatinization were significantly reduced. In pasting properties, tartary buckwheat and sorghum modified starch had the highest thermal treatment stability with lower setback and breakdown viscosity. Moreover, after three hours of starch hydrolysis; Resistant (RS) starch was higher in tartary buckwheat followed by broomcorn millet and lastly sorghum. In this study, we reported that tartary buckwheat modified starch is more useful in the preparation of food with thermal stability combined with a high amount of resistant starch.

The copper/graphene (Cu/Gr) composites made of Gr/Cu/Gr foils with a thickness of 25 μm were prepared using spark plasma sintering diffusion bonding (SPS) and hot press diffusion bonding (HP) in an Ar atmosphere at 900 °C for 20 min under a pressure of 50 MPa. The electrical conductivity of the prepared Cu/Gr composites was measured by the van der Pauw method, the microstructure was characterized using Raman spectroscopy, scanning electron microscope and transmission electron microscope, and the corresponding mechanism was analyzed by employing the first-principles calculations. The result indicates that, SPS process reduces the interfacial impurities of Cu/Gr composites, rendering a much higher electrical conductivity (108.6% IACS) than that prepared by using HP (98.8% IACS). This finding is correlated to the reduced oxygen (O) impurities on Gr/Gr interface, which is attributed to the high temperature plasma sputtering effect of SPS. In the prepared Cu/Gr composites, the impurity-free Gr/Gr interface has an ideal spacing of ∼3.3 Å wherein carbon (C) across the interface do not bond. Despite the generated C–C covalent bonding within the same Gr layer bounds some of the electrons, the remaining electrons of the p orbital on each C atom are free electrons, leading to the excellent electrical conductivity. In contrast, absorption of O impurities on the Gr/Gr interface increases the spacing between the Gr layers to ∼3.8 Å, and generates covalent C–O–C bonding across the interface due to p orbital hybridization. This reduces the free electron concentration and the corresponding electrical conductivity.

Objective: Inflammation and oxidative stress play critical roles in sepsis-induced acute lung injury (ALI). Sprout4 (Spry4) is involved in regulating inflammation and tissue injury; however, its role and mechanism in sepsis-induced ALI remain elusive. Methods: Macrophage-specific Spry4 knockout (Spry4MKO), transgenic (Spry4MTG) mice and matched control littermates were generated and exposed to cecum ligation and puncture (CLP) surgery to establish bacterial sepsis-induced ALI. Bone marrow-derived macrophages (BMDMs) from Spry4MKO or Spry4MTG mice were isolated and subjected to lipopolysaccharide (LPS) stimulation to further validate the role of Spry4 in vitro. To verify the necessity of AMP-activated protein kinase (AMPK), Spry4 and AMPK double knockout mice and compound C were used in vivo and in vitro. BMDMs were treated with STO-609 to inhibit calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2). Results: We found that macrophage Spry4 was increased in CLP mice and positively correlated with sepsis-induced ALI. Macrophage Spry4 deficiency prevented, while macrophage Spry4 overexpression exacerbated sepsis-induced inflammation, oxidative stress and ALI in mice and BMDMs. Mechanistic studies revealed that macrophage Spry4 deficiency alleviated sepsis-induced ALI through activating CaMKK2/AMPK pathway. Conclusion: Our study identify macrophage Spry4 as a promising predictive and therapeutic target of sepsis-induced ALI.

Recognizing multidrug-resistant (MDR) bacteria with high accuracy and precision from clinical samples has long been a difficulty. For reliable detection of MDR bacteria, we investigated a programmable molecular circuit called the Background-free isothermal circuital kit (BRICK). The BRICK method provides a near-zero background signal by integrating four inherent modules equivalent to the conversion, amplification, separation, and reading modules. Interference elimination is largely owing to a molybdenum disulfide nanosheets-based fluorescence nanoswitch and non-specific suppression mediated by molecular inhibitors. In less than 70 ​min, an accurate distinction of various MDR bacteria was achieved without bacterial lysis. The BRICK technique detected 6.73 ​CFU/mL of methicillin-resistant Staphylococcus aureus in clinical samples in a proof-of-concept trial. By simply reprogramming the sequence panel, such a high signal-to-noise characteristic has been proven in the four other superbugs. The proposed BRICK method can provide a universal platform for infection surveillance and environmental management thanks to its superior programmability.

Liver cancer presents a challenge in today’s healthcare system. This study aimed at investigating the effects of Fer-1 like family member 4 (FER1L4) on chemotherapy resistance and liver cancer development by using clinically collected liver cancer tissues and commercially purchased human liver cancer cisplatin-resistant cell line HUH-7/DDP. Bioinformatics analysis, dual luciferase reporter gene assay, and RNA pull-down were applied to predict and verify the possible binding relationships. The expressions of FER1L4, E2F transcription factor 1 (E2F1), microRNA-106a-5p (miR-106a-5p), or miR-372-5p were altered in the cells, followed by flow cytometry, Cell Counting Kit-8 (CCK-8), and Transwell assays to evaluate apoptotic, proliferative, and invasive abilities in vitro and nude mice xenografts to observe tumor growth in vivo. FER1L4 was highly expressed and miR-106-5p and miR-372-5p were poorly expressed in tumor cells and tissues. FER1L4 knockdown or the overexpression of miR-106-5p and miR-372-5p inhibited the cancerous cell proliferation and invasion while promoting apoptosis. FERIL4 silencing increased the miR-106-5p/miR-372-5p expression to inhibit the E2F1-activated nuclear factor κB (NF-κB) pathway. Besides, overexpressing FER1L4 led to an increased tumor growth in nude mice, which was reversed by the NF-κB inhibitor pyrollidine dithiocarbamate (PDTC). In conclusion, the results indicated that FER1L4 could inhibit the expression of miR-106a-5p/miR-372-5p, to activate E2F1-mediated NF-κB pathway, leading to drug resistance in liver cancer.

Bcr-Abl threonine 315 to isoleucine 315 (T315I) gatekeeper mutation induced drug resistance remains an unmet clinical challenge for the treatment of chronic myeloid leukemia (CML). Chemical degradation of Bcr-AblT315I protein has become a potential strategy to overcome drug resistance. Herein, we first described the design, synthesis, and evaluation of a new class of selective Bcr-AblT315I proteolysis-targeting chimeric (PROTAC) degraders based on GZD824 (reported as Bcr-AblT315I inhibitor by our group). One of the degrader 7o with 6-member carbon chain linkage with pomalidomide exhibits the most potent degradation efficacy with DR of 69.89% and 94.23% at 100 and 300 nmol/L, respectively, and has an IC50 value of 26.8 ± 9.7 nmol/L against Ba/F3T315I cells. Further, 7o also displays substantial tumor regression against Ba/F3-Bcr-AblT315I xenograft model in vivo.

Investigation of feces of wildlife, which is considered as reservoirs, melting pots, vectors and secondary sources of antimicrobial resistance genes (ARGs), provides insights into the risks and ecology of ARGs in the environment. Here, we investigated microbiomes, virulence factor genes (VFGs) of bacterial pathogens, and resistomes in environmental feces of Eurasian otters (Lutra lutra) and leopard cats (Prionailurus bengalensis) using shotgun metagenome sequencing. As expected, the taxonomic compositions of bacteria were significantly different between the animals. Importantly, we found that the compositions of ARGs were also significantly different between the animals. We detected ARGs including iri, tetA(P), tetB(P), floR, sulII, strA, strB, tetW and tetY. Some of them were significantly more abundant in either of the host animals, such as strA, strB and tetY in Eurasian otters, and tetA(P), tetW and iri in leopard cats. We also found that some ARGs were selectively correlated to particular VFGs-related bacteria, such as tetA(P) and tetB(P) to Clostridium, and iri to Mycobacterium. We also found that there were positive correlations between Acinetobacter and ARGs of multiple antimicrobial classes. The host-specific resistomes and VFGs-related bacteria may be due to differences in the host's gut microbiome, diet and/or habitat, but further investigation is needed. Overall, this study provided important baseline information about the resistomes of the wildlife in Korea, which may help the conservation of these endangered species and assessment of human health risks posed by ARGs and bacterial pathogens from wildlife.

Background: A growing body of studies have reported the health benefits of greenness. However, less is known about the potential beneficial effects of residential greenness on gut microbiota, which is essential to human health. In this study, we aim to examine the association between residential greenness and gut microbiota in a population-based cohort study. Methods: We included 1758 participants based on the China Multi-Ethnic Cohort (CMEC) study and collected their stool samples for 16S sequencing to derive gut microbiota data. Residential greenness was estimated using the satellite-based data on enhanced vegetation index (EVI) and the normalized differential vegetation index (NDVI) in circular buffers of 250 m, 500 m, and 1000 m. The relationships between residential greenness levels and the composition of gut microbiota, measured by standardized α-diversity and taxonomic composition, were assessed using linear regression and Spearman correlation weighted by generalized propensity scores. Results: Higher greenness levels were significantly positively associated with standardized α-diversity. Per interquartile range (IQR) increase of EVI and NDVI in the circular buffer of 250 m were associated with the increments of 0.995(95% confidence interval (CI): 0.212–1.778) and 0.653(95% CI: 0.160–1.146) in the standardized Shannon index. For the taxonomic composition of gut microbiota, higher greenness levels were significantly correlated with 29 types of microbial taxonomic composition. NDVI in the circular buffer of 250 m was associated with increased Firmicutes (r = 0.102, adjusted p value = 0.004), which was the dominant composition in the gut microbiota. Conclusions: Increased amounts of residential greenness may support healthy gut microbiota by benignly altering their composition. These findings suggested that green spaces should be designed to support diverse gut microbiota and ultimately optimize health benefits.

The most severe form of epilepsy, status epilepticus (SE), causes brain damage and results in the development of recurring seizures. Currently, the management of SE remains a clinical challenge because patients do not respond adequately to conventional treatments. Evidence suggests that neural cell death worsens the occurrence and progression of SE. The main forms of cell death are apoptosis, necroptosis, pyroptosis, and ferroptosis. Herein, these mechanisms of neuronal death in relation to SE and the alleviation of SE by potential modulators that target neuronal death have been reviewed. An understanding of these pathways and their possible roles in SE may assist in the development of SE therapies and in the discovery of new agents.

Cordycepin (Cor) is a potent bioactive constituent of Cordyceps militaris, which has been used as a daily tonic food and herbal medicine in Asia. Cadmium (Cd) is a widespread neurotoxic environmental contaminant, and it has been detected as a pollutant in Cordyceps militaris. However, the potential effects of Cor on Cd neurotoxicity remains unknown. This study aimed to investigate the effects and possible mechanisms of Cor on neurotoxicity in Cd-induced cell and preclinical models. It was observed that Cor administration aggravated Cd-induced cognitive impairment and neurotoxicity in mice, exerted synergistic growth inhibition, and promoted apoptosis of SH-SY5Y cells. These effects were found to be mediated through the activation of endoplasmic reticulum (ER) stress. Overall, our findings suggest that Cor can increase Cd-induced neurotoxicity via promoting ER stress-associated apoptosis. These observations may support the implementation of stricter criterion for the detection of Cd in Cordyceps militaris, to keep the consumers safe.

Background: Streptococcus suis (SS) is a major swine pathogen and a serious zoonotic pathogen causing septicemia and meningitis in piglets and humans. Using an immunoproteomic approach, we previously brought evidence that ornithine carbamoytransferase (OCT) may represent a vaccine candidate to protect against S. suis biofilm-related and acute infections. Method: In this study, the gene encoding OCT was cloned into the expression vector pET-28a and the recombinant protein was expressed in Escherichia coli BL21. The immunogenicity and protective efficacy of the SS OCT was further investigated in a mouse model. Results: The protein was found to be expressed in vivo and elicited high antibody titers following SS infections in mice. An animal challenge experiment with SS showed that 62.5% of mice immunized with the OCT protein were protected. Using an in vitro competitive adherence inhibition assay of adherence, evidence was obtained that OCT could significantly reduce the number of SS cells adhered to porcine kidney PK-15 cells. The bacterial levels recovered in mice of the OCT immunized group were significantly decreased in some organs, compared with the control group. Conclusion: In summary, our results suggest that the recombinant SS OCT protein, which is involved in bacterial adherence, may efficiently stimulate an immune response conferring protection against SS infections. It may therefore be considered as a potential vaccine candidate, although further studies are necessary to evaluate their use in swine. Keywords: Strepcotoccus suis, Ornithine carbamoyltransferase, Adherence, Vaccine

How plant competition varies with the changes of biotic and abiotic factors has been debated for a long time in the field of ecology. The aim of this study was to explore how neighbors and soil fertility influenced the intensity and importance of competition on species Stipa grandis and S. krylovii. We conducted a target species (S. grandis and S. krylovii) × soil fertility (low and high fertility) × competition treatment (4 treatments: two target species grown in monoculture and in mixture with each other, and in mixture with Leymus chinensis or Agropyron cristatum) microcosm experiment. We calculated the intensity (NIntA) and importance (NImpA) of neighbor-effect with additive symmetry for each target species under different treatments, and explored how the NIntA and NImpA were influenced by the target species, neighbor identity and soil fertility. We calculated the fertilizer-addition effect index on each target species to explore how neighbor identity influenced the index. (1) When target species in mixture with L. chinensis, both the NIntA and NImpA decreased with the increase of soil fertility. The NImpA was significantly negative on S. grandis under both soil fertility treatments and on S. krylovii under the high soil fertility treatment. (2) When target species in mixture with A. cristatum, the NIntA significantly influenced by the interaction between target species and soil fertility. The NImpA was significantly negative on S. grandis under the low soil fertility treatment and on S. krylovii under the high soil fertility treatment. (3) When in S. grandis – S. krylovii mixture system, the NIntA increased with the increase of soil fertility, and the NImpA showed no significant effects on each target species. (4) The fertilizer-addition effect was higher than zero for all treatments except the one on S. grandis in mixture with L. chinensis. The effect on S. krylovii was relatively lower than that on S. grandis in mixture with A. cristatum but was relatively higher in any of the other three competition treatments. The present findings demonstrated that the identities of both target and neighbor species influenced the fertilizer-addition effect and the responses of intensity and importance of competition to the changes of soil fertility. The present study showed the complexity of target species and neighbor identities in influencing the outcomes of plant competition, and provided novel insights into how plant competition driving the community dynamics in the context of soil fertility changes.

Herein, a printing strategy was proposed and expended, which allows fabricating diverse geometries of cellular continuous fiber-reinforced composites (CFRCs) with fiber distribution and interlacement in the cellular structure uniformly. A class of printed triangle-filled cellular structure composites was prepared to present the detail of the printing strategy. The effects of printing and structural parameters on the mechanical properties, as well as shape memory performance of printed CFRCs, were studied precisely, and thereafter, a Finite Element (FE) model was developed on the basis of the printing path to stimulate and analyze the tensile process. Experimental results showed that introducing only 3.8% fiber content into the composite can significantly improve the tensile strength by more than 300%. An increment of cell length was capable of strengthening tensile features compellingly due to changing orientation and alignment degree of fiber in the structure. By contrast, sizing the cell length and embedding further fiber have represented a reverse pattern against the composite's shape recovery ratio, which witnessed an adverse impact on shape-changing materials. A conclusion was given that the mechanical properties and shape memory effect of the 3D-printed continuous fiber-reinforced composite can be optimized by adjusting the geometric parameters and fiber content.

Retinal ischemia reperfusion injury (IRI) is a leading cause of visual impairment or blindness, and an effective way to prevent the visual loss needs to be developed. Although decades of clinical application of Huoxue-Tongluo-Lishui-Decoction (HTLD) has demonstrated its reliable clinical efficacy against retinal IRI, no convincing randomized controlled trials were conducted in humans or animals, and the associated mechanism still needs to be explored. To confirm the protective effect of HTLD against retinal IRI and to explore its underlying mechanisms, a standard retinal IRI animal model, randomized controlled trials, objective evaluation and examination methods were adopted in this study. Flash visual evoked potentials (F-VEP) was performed 8 weeks post-reperfusion. The results showed that the medium dose of HTLD had better treatment effects than low dose of HTLD. High dose of HTLD did not further improve visual function relative to medium dose of HTLD, but had poor performance in the latency of P2 wave. The angio-optical coherence tomography (angio-OCT) examination showed that retinal nerve fiber layer (RNFL) became edematous in the early stage, then the edema subsided, and RNFL became thinning in the late stage. HTLD reduced the swelling of RNFL in the early stage and prevented the thinning of RNFL in the late stage. Similar to F-VEP, medium dose of HTLD has the best neural-protective effects against retinal IRI. In mechanisms, HTLD treatment not only enhanced autophagy at 6 h after reperfusion, but extended the enhancing effect until at least 24 h. HTLD treatment significantly reduced the cleaved Caspase-3, cleaved PARP and Caspase-3 activity at 48 h after reperfusion. HTLD inhibited neuro-toxic cytokines expression in retinal IRI by modulating Akt/NF-kB signaling. HTLD treatment enhanced the expressions of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS), and lower the concentration of free glutamate in retina after reperfusion. The phosphorylation of iNOS increased significantly in retinal IRI at 6 h, and HTLD treatment suppressed the phosphorylation of Inducible nitric oxide synthetase (iNOS). In conclusion, HTLD is visual-protective against retinal IRI, and the regulation of autophagy, apoptosis and neuro-toxic mediators may be the underlying mechanisms. These findings may provide new ideas for the clinical treatment of retinal IRI related diseases.

GZD824 is a novel third-generation BCR-ABL inhibitor. It entered Phase II clinical trials in China and Phase Ib clinical trials in USA in 2019 for treatment of patients with resistant chronic myeloid leukemia (CML). We found that at concentrations below 10 nM, GZD824 significantly suppresses FLT3, FGFR1 and PDGFRα kinase activities and inhibits their signal pathways in MV4-11Flt3-ITD, KG-1FGFR1OP2-FGFR1 and EOL-1FIP1L1-PDGFRa leukemia cells. It selectively inhibits the growth of MV4-11Flt3-ITD, KG-1FGFR1OP2-FGFR1 and EOL-1FIP1L1-PDGFRa cells, and also effectively suppresses the growth of Ba/F3-FLT3-ITD cells harboring F691I and other mutations with IC50 values

We present a practical computational framework for the coarse-graining of cross-linked epoxies by developing a machine-learning technique, which integrates molecular dynamics simulations with artificial neural network (ANN) assisted particle swarm optimization (PSO) algorithm. Key features of the framework include two aspects: (1) determining the bonded interactions via the iterative Boltzmann inversion method to emulate the local structures of the epoxies and, (2) optimizing the nonbonded interaction potentials through the machine-learning approach to reproduce the mechanical properties. Such machine-learning based technique is computationally efficient in searching for the optimal solution of nonbonded potential parameters and enables the CG model to become transferable within a wide range of cross-linking degrees. This is mainly attributed to the fact that ANN can give good predictions based on training database obtained from CG simulations and thus greatly accelerates the PSO algorithm in achieving the optimal solution. On the basis of the DOC-transferable CG model, the cohesive interaction strength is phenomenologically adjusted to preserve the temperature-dependent properties. The CG model allows the mechanical properties of cross-linked epoxies to be predicted with reasonable accuracy over wide ranges of cross-linking degrees and temperature. The proposed framework will become highly beneficial to the design of high performance epoxy-matrix nanocomposites. Keywords: Machine-learning approach, Cross-linked epoxy, Coarse-grained model, Molecular dynamics

In this paper, we demonstrated that a 90°-bended imaging of spoof surface acoustic waves with subwavelength resolution of 0.316λ can be realized by a 45° prism-shaped surface phononic crystal (SPC), which is composed of borehole arrays with square lattice in a rigid plate. Furthermore, by combining two identical prism-shaped phononic crystal to form an interface (to form a line-defect), the excited spoof surface acoustic waves can be split into bended and transmitted parts. The power ratio between the bended and transmitted surface waves can be tuned arbitrarily by adjusting the defect size. This acoustic system is believed to have potential applications in various multifunctional acoustic solutions integrated by different acoustical devices.

Background: Phalaenopsis is an important ornamental flowering plant that belongs to the Orchidaceae family and is cultivated worldwide. Phalaenopsis has a long juvenile phase; therefore, it is important to understand the genetic elements regulating the transition from vegetative phase to reproductive phase. In this study, FLOWERING LOCUS T (FT) homologs in Phalaenopsis were cloned, and their effects on flowering were analyzed. Results: A total of five FT-like genes were identified in Phalaenopsis. Phylogenetic and expression analyses of these five FT-like genes indicated that some of these genes might participate in the regulation of flowering. A novel FT-like gene, PhFT-1, distantly related to previously reported FT genes in Arabidopsis and other dicot crops, was also found to be a positive regulator of flowering as heterologous expression of PhFT-1 in Arabidopsis causes an early flowering phenotype. Conclusions: Five FT homologous genes from Phalaenopsis orchid were identified, and PhFT-1 positively regulates flowering.

This paper describes the combinational surface kinetics enhancement and surface states passivation of nickel-borate (Ni-Bi) co-catalyst for a hematite (Fe2O3) photoanode. The Ni-Bi-modified Fe2O3 photoanode exhibits a cathodic onset potential shift of 230 mV and a 2.3-fold enhancement of the photocurrent at 1.23 V, versus the reversible hydrogen electrode (RHE). The borate (Bi) in the Ni-Bi film promotes the release of protons for the oxygen evolution reaction (OER).

Here we provide data describing the time-course of blood-glucose and fluid-intake profiles of diabetic hemizygous human-amylin (hA) transgenic mice orally treated with rutin, and matched control mice treated with water. We employed “parametric change-point regression analysis” for investigation of differences in time-course profiles between the control and rutin-treatment groups to extract, for each animal, baseline levels of blood glucose and fluid-intake, the change-point time at which blood glucose (diabetes-onset) and fluid-intake (polydipsia-onset) accelerated away from baseline, and the rate of this acceleration. The parametric change-point regression approach applied here allowed a much more accurate determination of the exact time of onset of diabetes than do the standard diagnostic criteria. These data are related to the article entitled “Rutin suppresses human-amylin/hIAPP misfolding and oligomer formation in-vitro, and ameliorates diabetes and its impacts in human-amylin/hIAPP transgenic mice” (J.F. Aitken, K.M. Loomes, I. Riba-Garcia, R.D. Unwin, G. Prijic, A.S. Phillips, A.R.J. Phillips, D. Wu, S.D. Poppitt, K. Ding, P.E. Barran, A.W. Dowsey, G.J.S. Cooper. 2016) [1].

In this paper, we present a study of acoustic wave propagation in layered sonic crystals (SCs) with periodic slits, and demonstrate the extraordinary acoustic refractions induced by acoustic backward and forward wave effects in SCs. By tuning the parameters of geometry structures and incident angles of acoustic waves, the positive, negative and zero acoustic refractions are demonstrated respectively. Taking advantage of the exotic acoustic refraction, we present the splitting of acoustic beams through the layered SCs, which is a new method to achieve acoustic beam splitting. Keywords: Sonic crystals, Backward effects, Forward effects, Beam splitting

This review delves into the burgeoning field of explainable artificial intelligence (XAI) in the detection and analysis of lung diseases through vocal biomarkers. Lung diseases, often elusive in their early stages, pose a significant public health challenge. Recent advancements in AI have ushered in innovative methods for early detection, yet the black-box nature of many AI models limits their clinical applicability. XAI emerges as a pivotal tool, enhancing transparency and interpretability in AI-driven diagnostics. This review synthesizes current research on the application of XAI in analyzing vocal biomarkers for lung diseases, highlighting how these techniques elucidate the connections between specific vocal features and lung pathology. We critically examine the methodologies employed, the types of lung diseases studied, and the performance of various XAI models. The potential for XAI to aid in early detection, monitor disease progression, and personalize treatment strategies in pulmonary medicine is emphasized. Furthermore, this review identifies current challenges, including data heterogeneity and model generalizability, and proposes future directions for research. By offering a comprehensive analysis of explainable AI features in the context of lung disease detection, this review aims to bridge the gap between advanced computational approaches and clinical practice, paving the way for more transparent, reliable, and effective diagnostic tools., Competing Interests: Declaration of competing interest As the authors of the manuscript titled "Exploring Explainable AI Features in the Vocal Biomarkers of Lung Disease," we declare that there are no conflicts of interest regarding the publication of this paper. We have no financial, consultant, institutional, or other relationships that might lead to a conflict of interest. All data and materials support our published claims and comply with field standards. Furthermore, there has been no significant ethical concern in the conduct of this research. Our submission is in agreement with all authors, and we collectively take responsibility for the work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fibrosis, a pathological state characterized by the excessive accumulation of extracellular matrix components, is primarily driven by the overactivation of fibroblasts. This condition becomes particularly pronounced under chronic inflammatory conditions. Fibrosis can occur in several tissues throughout the body. Among the notable discoveries in the study of fibrosis is the role of Collagen Triple Helix Repeat Containing-1 (CTHRC1), a protein that has emerged as a critical regulator in the fibrotic process. CTHRC1 is rapidly expressed on the outer membrane of fibroblasts and intimal smooth muscle cells following vascular injury, such as that induced by balloon angioplasty. This expression denotes the organism efforts to repair and restructure compromised tissue, signifying a critical component of the tissue repair mechanism in reaction to fibrosis. It plays a pivotal role in promoting cell migration and aiding tissue repair post-injury, contributing significantly to various pathophysiological processes including revascularization, bone formation, developmental morphological changes, inflammatory arthritis, and the progression of cancer. Significantly, researchers have observed marked expression of CTHRC1 across a variety of fibrotic conditions, closely associating it with the progression of the disease. Intervention with CTHRC1 can affect the occurrence and progression of fibrosis. This review aims to comprehensively explore the role and underlying mechanisms of CTHRC1 in fibrotic diseases, highlighting its potential as a key target for therapeutic interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Intraparticle domains are the critical locations for storing contaminants and retarding contaminant transport in subsurface environments. While the kinetics and extent of antibiotics sorption and desorption in subsurface materials have been extensively studied, their behaviors in intraparticle domains have not been well understood. This study investigated the sorption and desorption of antibiotics (ATs) in the intraparticle domains using quartz grains and clay, and antibiotic tetracycline (TC) and levofloxacin (LEV) as examples that are commonly present in groundwater systems. Batch experiments coupled with the analyses using various microscopic and spectroscopic techniques were performed to investigate the sorption and desorption kinetics, and to provide insights into the intraparticle sorption and desorption of TC and LEV. Results indicated that both TC and LEV with different physiochemical properties can migrate into intraparticle domains that were consistent with sorptive diffusion. The rate and extent of the sorption are a function of intraparticle surface area and properties, pore volume and connectivity, and ionic properties of the ATs. The sorptive diffusion led to the slow desorption of both TC and LEV after their sorption, apparently showing an irreversible desorption behavior (with desorption percentage about 1.86-20.51%). These results implied that intraparticle domains can be important locations for storing ATs, retarding ATs transport, and may serve as a long-term secondary source for groundwater contamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Curcumin ameliorates bone loss by inhibiting osteoclastogenesis. Curcumin inhibits RANKL-promoted autophagy in osteoclast precursors (OCPs), which mediates its anti-osteoclastogenic effect. But the role of RANKL signaling in curcumin-regulated OCP autophagy is unknown. This study aimed to explore the relationship between curcumin, RANKL signaling, and OCP autophagy during osteoclastogenesis., Methods: We investigated the role of curcumin in RANKL-related molecular signaling in OCPs, and identified the significance of RANK-TRAF6 signaling in curcumin-treated osteoclastogenesis and OCP autophagy using flow sorting and lentiviral transduction. Tg-hRANKL mice were used to observe the in vivo effects of curcumin on RANKL-regulated bone loss, osteoclastogenesis, and OCP autophagy. The significance of JNK-BCL2-Beclin1 pathway in curcumin-regulated OCP autophagy with RANKL was explored via rescue assays and BCL2 phosphorylation detection., Results: Curcumin inhibited RANKL-related molecular signaling in OCPs, and repressed osteoclast differentiation and autophagy in sorted RANK + OCPs but did not affect those of RANK - OCPs. Curcumin-inhibited osteoclast differentiation and OCP autophagy were recovered by TRAF6 overexpression. But curcumin lost these effects under TRAF6 knockdown. Furthermore, curcumin prevented the decrease in bone mass and the increase in trabecular osteoclast formation and autophagy in RANK + OCPs in Tg-hRANKL mice. Additionally, curcumin-inhibited OCP autophagy with RANKL was reversed by JNK activator anisomycin and TAT-Beclin1 overexpressing Beclin1. Curcumin inhibited BCL2 phosphorylation at Ser70 and enhanced protein interaction between BCL2 and Beclin1 in OCPs., Conclusions: Curcumin suppresses RANKL-promoted OCP autophagy by inhibiting signaling pathway downstream of RANKL, contributing to its anti-osteoclastogenic effect. Moreover, JNK-BCL2-Beclin1 pathway plays an important role in curcumin-regulated OCP autophagy., Competing Interests: Conflicts of interest The authors declare that there is no conflict of interests., (© 2023 Chang Gung University. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Diabetic patients often experience long-term risks due to chronic inflammation and delayed re-epithelialization during impaired wound healing. Although the severity of this condition is well known, the treatment options for diabetic wounds are limited. Rhubarb charcoal, a well-known traditional Chinese medicine, has been used to treat skin wounds for thousands of years. We produced a chitosan/silk fibroin sponge scaffold loaded with natural carbonized rhubarb and crosslinked it by freeze-drying to create a highly efficient RCS/SF scaffold. Rhubarb carbon and carboxymethyl chitosan exhibit antibacterial activity and promote wound healing. Owing to its 3D porous structure, this scaffold is antibacterial and pro-angiogenic. It also possesses remarkable properties, such as excellent swelling and biocompatibility. The supportive effect of carbonized rhubarb on mouse fibroblast migration is mediated at the cellular/tissue level by increased skin neovascularization and re-epithelization. Compared to the control group, RCS/SF scaffolds promoted faster healing, increased neovascularization, enhanced collagen deposition, and re-epithelialization within two weeks. The scaffold's pro-healing properties and efficient release of carbonized rhubarb, with rapid hemostatic and good sterilization effects, make it an outstanding candidate for treating diabetic wounds and novel therapeutic interventions for diabetic ulcers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Aims: Immunotherapy has shown remarkable effects on several malignancies; however, its impact on gastric cancers has been limited. Therefore, a novel strategy to overcome resistance to immunotherapy is required. In this study, we compared the gene expression profiles of two murine GC cell lines that exhibited different effects on tumor immunity. The functions of specific genes related to negative tumor immunity and the impact of a specific inhibitor were evaluated in syngeneic GC mouse models., Materials and Methods: RT-PCR and Western blotting validated Gas6 and AXL expression in murine cell lines. RT-PCR compared YTN16 and YTN3 GC cell's impact on T cell activation. AXL, the receptor for GAS6 in YTN16, was validated by western blotting. Gas6 was inhibited in YTN16 cells using shRNA, and then the gene expression pattern, effects to T cell activation, and tumor growth were assessed. YTN16 cells were injected into mice and treated with CCB-3233, anti-PD-1 antibody, or both. Immunohistochemistry and flow cytometry evaluated tumor-infiltrating immune cells., Key Findings: YTN16 cells expressed more Gas6 and had reduced T cell activation compared to YTN3 cells. AXL activation was higher in YTN16. CCB-3233 reduced AXL phosphorylation. Knocking down Gas6 in YTN16 reduced immunosuppression-related genes and increased tumor-infiltrating T cells. Combined CCB-3233 and anti-PD-1 treatment reduced tumor growth and increased T-cell infiltration. Human GC data revealed a negative correlation between GAS6 and immune activation-related genes., Significance: The GAS6/AXL pathway contributes to immunotherapy resistance in GC. Targeting this pathway may be a novel therapeutic strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cervical cancer is one of the most leading causes of cancer death worldwide, and ferroptosis is implicated in the progression of cervical cancer. Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) is involved in the progression of various human cancers; however, its function in cervical cancer remains unclear. The present study aims to investigate the role and mechanism of CNIH4 in cervical cancer using gain- and loss-of-function studies in vitro. SiHa and CaSki cells were infected with lentiviral vectors to manipulate the expression of CNIH4 in vitro, and cell viability, migration, invasion as well as ferroptosis were evaluated. Transcriptome sequencing analysis was performed to further validate the mechanism through which CNIH4 regulated the progression of cervical cancer. The expression of CNIH4 was upregulated in human cervical cancer tissues and cells, and strongly correlated with the decreases in overall survival and disease free survival rates of cervical cancer patients. CNIH4 silence inhibited, while CNIH4 overexpression facilitated the survival of human cervical cancer cells. Mechanistically, CNIH4 elevated solute carrier family 7 member 11 (SLC7A11)-mediated cystine import, and subsequently increased intracellular glutathione synthesis and glutathione peroxidase 4 activity, thereby inhibiting ferroptosis of human cervical cancer cells. SLC7A11 silence significantly abolished CNIH4-mediated inhibition of ferroptosis in cervical cancer cells in vitro. Our study for the first time reveals that CNIH4 inhibits ferroptosis of human cervical cancer cells through upregulating SLC7A11, defining CNIH4 as an attractive therapeutic and prognostic target for cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Researchers agree that there is substantial evidence of an increasing trend in both the frequency and duration of extreme temperature events. Increasing extreme temperature events will place more pressure on public health and emergency medical resources, and societies will need to find effective and reliable solutions to adapt to hotter summers. This study developed an effective method to predict the number of daily heat-related ambulance calls. Both national- and regional-level models were developed to evaluate the performance of machine-learning-based methods on heat-related ambulance call prediction. The national model showed a high prediction accuracy and can be applied over most regions, while the regional model showed extremely high prediction accuracy in each corresponding region and reliable accuracy in special cases. We found that the introduction of heatwave features, including accumulated heat stress, heat acclimatization, and optimal temperature, significantly improved prediction accuracy. The adjusted coefficient of determination (adjusted R 2 ) of the national model improved from 0.9061 to 0.9659 by including these features, and the adjusted R 2 of the regional model also improved from 0.9102 to 0.9860. Furthermore, we used five bias-corrected global climate models (GCMs) to forecast the total number of summer heat-related ambulance calls under three different future climate scenarios nationally and regionally. Our analysis demonstrated that, at the end of the 21st century, the total number of heat-related ambulance calls in Japan will reach approximately 250,000 per year (nearly four times the current amount) under SSP-5.85. Our results suggest that disaster management agencies can use this highly accurate model to forecast potential high emergency medical resource burden caused by extreme heat events, allowing them to raise and improve public awareness and prepare countermeasures in advance. The method proposed in Japan in this paper can be applied to other countries that have relevant data and weather information systems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Deng Ke reports financial support was provided by National Institute for Environmental Studies. The Corresponding author completed this study during an internship at the National Institute for Environmental Studies (NIES), Japan., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The transport and retention of microorganisms are typically described using attachment/detachment and straining/liberation models. However, the parameters in the models varied significantly, posing a significant challenge to describe microbial transport under different environmental conditions. A neural network (ANN) model was developed in this study to link the parameters in the model with the factors influencing microbial transport including the properties of microorganisms such as size and surface potentials, and the properties of porous media such as grain size and porosity, and flow conditions. Exhaustive search of literature renders 420 sets of experimental data of microbial transport, which were fitted using the microbial transport model to obtain model parameters. The model parameters, together with the factors influencing microbial transport, were then used to train an ANN model to search for their relationship. An ANN-based parameter relationship was derived and was then used to simulate microbial transport. The simulated results using the relationship roughly matched with the experimental data under different environmental conditions, indicating that a unified relationship was established between the parameters of the microbial transport model and the factors influencing microbial transport, and that microbial transport can be described using the microbial transport model with the ANN-based unified relationship for model parameters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)