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Abstract Primary retroperitoneal liposarcoma (RLPS) is a rare heterogeneous tumor occurring within retroperitoneal space, and its overall survival has not improved much in the past few decades. Based on a small-sample clinical practice at our center, patients with RLPS can greatly benefit from anlotinib and eribulin combination. In this study, we investigated the combinational effect of anlotinib and eribulin on RLPS. In vitro experiments revealed that a low dose of anlotinib significantly enhances the cytotoxic effects of eribulin, leading to a remarkable suppression of RLPS cell proliferation, viability, colony formation, migration, and cell-cycle progression compared to individual drug treatments. At the organoid level, the combination treatment causes the spheroids in Matrigel to disintegrate earlier than the single-drug group. In vivo, RLPS patient-derived xenograft (PDX) models demonstrated that the combination of these two drugs can obviously exert a safe and effective anti-tumor effect. Through transcriptome analysis, we uncovered and validated that the synergistic effect mainly is induced by the endoplasmic reticulum stress (ERS) pathway both in vitro and in vivo. Further analyses indicate that anlotinib plus eribulin treatment results in micro-vessel density and PD-L1 expression alterations, suggesting a potential impact on the tumor microenvironment. This study extensively explored the combination regimen at multiple levels and its underlying molecular mechanism in RLPS, thus providing a foundation for translational medicine research.

Author(s): DAMPE Collaboration; G. Ambrosi [1]; Q. An [2, 3]; R. Asfandiyarov [4]; P. Azzarello [4]; P. Bernardini [5, 6]; B. Bertucci [1, 7]; M. S. Cai [8, 9]; J. [...]

Abstract Chronic Painful Temporomandibular Disorders (TMD) are challenging to diagnose and manage due to their complexity and lack of understanding of brain mechanism. In the past few decades’ neural mechanisms of pain regulation and perception have been clarified by neuroimaging research. Advances in the neuroimaging have bridged the gap between brain activity and the subjective experience of pain. Neuroimaging has also made strides toward separating the neural mechanisms underlying the chronic painful TMD. Recently, Artificial Intelligence (AI) is transforming various sectors by automating tasks that previously required humans’ intelligence to complete. AI has started to contribute to the recognition, assessment, and understanding of painful TMD. The application of AI and neuroimaging in understanding the pathophysiology and diagnosis of chronic painful TMD are still in its early stages. The objective of the present review is to identify the contemporary neuroimaging approaches such as structural, functional, and molecular techniques that have been used to investigate the brain of chronic painful TMD individuals. Furthermore, this review guides practitioners on relevant aspects of AI and how AI and neuroimaging methods can revolutionize our understanding on the mechanisms of painful TMD and aid in both diagnosis and management to enhance patient outcomes.

Abstract Emerging evidence indicates that SOX2 is an oncogene for esophageal squamous cell carcinoma (ESCC). However, direct targeting of SOX2 is not feasible given that this transcription factor plays important roles in the maintenance of tissues such as the brain. Here, we identified CDP (Homeobox protein cut-like 1 or CASP) as a unique SOX2 binding partner enriched in ESCC with Duolink proximity ligation assay, bimolecular fluorescence complementation (BiFc) and immunoprecipitation. We then screened a peptide aptamer library using BiFc and immunoprecipitation and identified several peptide aptamers, including P58, that blocked the CDP/SOX2 interaction, leading to the inhibition of ESCC progress in vitro and in vivo. Upon administration, synthetic peptide P58, containing the YGRKKRRQRRR cell-penetrating peptide and the fluorophore TAMRA, also blocked the growth and metastasis of ESCC in both mice and zebrafish. Therefore, targeting the SOX2 binding partner CDP with peptide P58 offers an alternative avenue to treat ESCC with increased SOX2 levels.

Abstract Ferroptosis is a form of regulated cell death induced by iron-dependent lipid peroxidation, and it has been studied extensively since its discovery in 2012. Induced by iron overload and ROS accumulation, ferroptosis is modulated by various cellular metabolic and signaling pathways. The GSH-GPX4 pathway, the FSP1-CoQ10 pathway, the GCH1-BH4 pathway, the DHODH-CoQH2 system and the sex hormones suppress ferroptosis. Mitochondrial iron metabolism regulates ferroptosis and mitochondria also undergo a morphological change during ferroptosis, these changes include increased membrane density and reduced mitochondrial cristae. Moreover, mitochondrial energy metabolism changes during ferroptosis, the increased oxidative phosphorylation and ATP production rates lead to a decrease in the glycolysis rate. In addition, excessive oxidative stress induces irreversible damage to mitochondria, diminishing organelle integrity. ROS production, mitochondrial membrane potential, mitochondrial fusion and fission, and mitophagy also function in ferroptosis. Notably, some ferroptosis inhibitors target mitochondria. Ferroptosis is a major mechanism for cell death associated with the progression of cancer. Metastasis-prone or metastatic cancer cells are more susceptible to ferroptosis. Inducing ferroptosis in tumor cells shows very promising potential for treating drug-resistant cancers. In this review, we present a brief retrospect of the discovery and the characteristics of ferroptosis, then we discuss the regulation of ferroptosis and highlight the unique role played by mitochondria in the ferroptosis of cancer cells. Furthermore, we explain how ferroptosis functions as a double-edged sword as well as novel therapies aimed at selectively manipulating cell death for cancer eradication.

Abstract Cancer stem cells(CSCs) play a key role in regulating tumorigenesis, progression, as well as recurrence, and possess typical metabolic characteristics. Autophagy is a catabolic process that can aid cells to survive under stressful conditions such as nutrient deficiency and hypoxia. Although the role of autophagy in cancer cells has been extensively studied, CSCs possess unique stemness, and their potential relationship with autophagy has not been fully analyzed. This study summarizes the possible role of autophagy in the renewal, proliferation, differentiation, survival, metastasis, invasion, and treatment resistance of CSCs. It has been found that autophagy can contribute to the maintenance of CSC stemness, facilitate the tumor cells adapt to changes in the microenvironment, and promote tumor survival, whereas in some other cases autophagy acts as an important process involved in the deprivation of CSC stemness thus leading to tumor death. Mitophagy, which has emerged as another popular research area in recent years, has a great scope when explored together with stem cells. In this study, we have aimed to elaborate on the mechanism of action of autophagy in regulating the functions of CSCs to provide deeper insights for future cancer treatment.

Amino-acid and structural similarities between the newly discovered E5-1 gene on chromosome 1 and the S182 gene on chromosome 14q24.3 along with their associations with early-onset familial Alzheimer's disease subtype AD3 indicate the existence of other AD susceptibility genes. Both genes have missense mutations that are present in persons with AD3, suggesting that they serve similar functions on the same biochemical pathway with aberrations leading to heightened Alzheimer's risk.

The locus AD3 which encodes 19 different transcripts is associated with susceptibility to an aggressive early-onset form of Alzheimer's disease (AD). Samples taken from sufferer of this form of AD show five missense mutations in S182, one of the transcripts encoded by AD3 but non-sufferers do not show these mutations. The mutations involve heterozygous nucleotide substitution and may cause early-onset of AD. Studies show that the S182 protein is an integral membrane protein which might be either a receptor or channel protein.

Abstract Diabetic nephropathy (DN) is one of the serious chronic microvascular complications of diabetes, and leads to the increased morbidity and mortality in diabetic patients. Gasdermin E (GSDME)-dependent pyroptosis signaling pathway plays important roles in a variety of physiological and pathological processes. However, its role and mechanism in DN are still unclear. In this study, we established a rat DN model by intraperitoneal injection of streptozotocin (STZ) successfully. Structural and functional disorders in the kidney were exhibited on the 12th week after STZ injection; the expressions of caspase-3 and GSDME at protein level in renal cortex were significantly up-regulated. At the 20th week, GSDME-N increased significantly, accompanied by the upregulation of caspase-1 in renal cortex and the release of mature IL-1β (mIL-1β) in serum. Furthermore, we found the protein levels of GSDME, caspase-3, caspase-1 and IL-1β were all increased in HK2 and HBZY-1 cells under high-glucose conditions. We also found that the expression of GSDME-N significantly decreased when caspase-3 was knockdown. In contrast, knockdown of GSDME has no effect on caspase-3. Interestingly, either caspase-3, caspase-1 or GSDME knockdown reduced the release of mIL-1β. Finally, injection of adeno-associated virus (AAV) 9-shGSDME into the rat kidney reduced kidney damage and renal cell pyroptosis in comparison with wild-type diabetic rats. These results indicated that the activation of caspase-1 induced IL-1β maturation, and the activation of caspase-3 mediated cleavage of GSDME responsible for the formation of plasma membrane pore, followed by cytoplasmic release of mIL-1β. Overall, we identified a pro-pyroptosis role for GSDME in DN, which does provide an important basis for clinical therapeutic studies.

Abstract Hepatocellular carcinoma (HCC), one of the most malignant tumors, is characterized by its stubborn immunosuppressive microenvironment. As one of the main members of the tumor microenvironment (TME) of HCC, tumor-associated macrophages (TAMs) play a critical role in its occurrence and development, including stimulating angiogenesis, enhancing immunosuppression, and promoting the drug resistance and cancer metastasis. This review describes the origin as well as phenotypic heterogeneity of TAMs and their potential effects on the occurrence and development of HCC and also discusses about various adjuvant therapy based strategies that can be used for targeting TAMs. In addition, we have highlighted different treatment modalities for TAMs based on immunotherapy, including small molecular inhibitors, immune checkpoint inhibitors, antibodies, tumor vaccines, adoptive cellular immunotherapy, and nanocarriers for drug delivery, to explore novel combination therapies and provide feasible therapeutic options for clinically improving the prognosis and quality of life of HCC patients.

Abstract Sepsis is a systemic inflammatory syndrome (SIRS) caused by acute microbial infection, and it has an extremely high mortality rate. Tumor necrosis factor-α (TNF-α)-induced necroptosis contributes to the pathophysiology of sepsis, so inhibiting necroptosis might be expected to improve clinical outcomes in septic patients. Here we predicted candidate drugs for treating sepsis in silico by combining genes differentially expressed in septic patients and controls combined with interrogation of the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 perturbation database. Sixteen candidate drugs were screened out through bioinformatics analysis, and the top candidate linifanib was validated in cellular and mouse models of TNF-α-induced necroptosis. Cell viability was measured using a luminescent ATP assay, while the effects of linifanib on necroptosis were investigated by western blotting, immunoprecipitation, and RIPK1 kinase assays. Linifanib effectively protected cells from necroptosis and rescued SIRS mice from TNF-α-induced shock and death. In vitro, linifanib directly suppressed RIPK1 kinase activity. In vivo, linifanib effectively reduced overexpressed IL-6, a marker of sepsis severity, in the lungs of SIRS mice. Our preclinical evidence using an integrated in silico and experimental drug repositioning approach supports the potential clinical utility of linifanib in septic patients. Further clinical validation is now warranted.

Abstract The solar X-ray and Extreme Ultraviolet Imager (X-EUVI), developed by the Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), is the first space-based solar X-ray and Extreme ultraviolet (EUV) imager of China loaded on the Fengyun-3E (FY-3E) satellite supported by the China Meteorological Administration (CMA) for solar observation. Since started work on July 11, 2021, X-EUVI has obtained many solar images. The instrument employs an innovative dual-band design to monitor a much larger temperature range on the Sun, which covers 0.6–8.0 nm in the X-ray region with six channels and 19.5 nm in the EUV region. X-EUVI has a field of view of 42′, an angular resolution of 2.5″ per pixel in the EUV band and an angular resolution of 4.1″ per pixel in the X-ray band. The instrument also includes an X-ray and EUV irradiance sensor (X-EUVS) with the same bands as its imaging optics, which measures the solar irradiance and regularly calibrates the solar images. The radiometric calibration of X-EUVS on the ground has been completed, with a calibration accuracy of 12%. X-EUVI is loaded on the FY-3E satellite and rotates relative to the Sun at a uniform rate. Flat-field calibration is conducted by utilizing successive rotation solar images. The agreement between preliminarily processed X-EUVI images and SDO/AIA and Hinode/XRT images indicates that X-EUVI and the data processing algorithm operate properly and that the data from X-EUVI can be applied to the space weather forecast system of CMA and scientific investigations on solar activity.

Abstract Mesenchymal/stromal stem cells (MSCs) are a crucial component of the tumour microenvironment (TME). They can be recruited from normal tissues into the TME and educated by tumour cells to transform into tumour-associated MSCs, which are oncogenic cells that promote tumour development and progression by impacting or transforming into various kinds of cells, such as immune cells and endothelial cells. Targeting MSCs in the TME is a novel strategy to prevent malignant processes. Exosomes, as communicators, carry various RNAs and proteins and thus link MSCs and the TME, which provides options for improving outcomes and developing targeted treatment.

Abstract The activity of integrin-linked kinase (ILK) in cancerous cells is often oncogenic and associated with malignant properties, such as uncontrolled cell cycle progression and evasion from senescence. However, the role of ILK in cellular senescence in gastric cancer (GC) has not been previously examined. We generated single-cell clones of ILK knock-out using CRISPR-Cas9 in human GC lines with mesenchymal or epithelial histology. Cells with no residual ILK expression exhibited strong cellular senescence with diminished clathrin-mediated endocytosis, Surprisingly, ILK loss-induced cellular senescence appeared to be independent of its function in integrin signaling. The low dose of CPD22, a small molecule inhibitor of ILK activity-induced senescence in three GC cell lines with different histologies. Furthermore, senescent cells with ILK depletion transfected with N-terminal truncated ILK mutant remaining catalytic domains displayed the reduction of senescent phenotypes. RNA sequencing and cytokine array results revealed the enrichment of multiple pro-inflammatory signaling pathways in GC lines in the absence of ILK. Our study identified the important role and the potential mechanism of ILK in the cellular senescence of cancerous epithelial cells. The inhibition of ILK activity using small molecule compounds could have a pro-senescent effect as a therapeutic option for GC.

Abstract A high intratumoral nerve density is correlated with poor survival, high metastasis, and high recurrence across multiple solid tumor types. Recent research has revealed that cancer cells release diverse neurotrophic factors and exosomes to promote tumor innervation, in addition, infiltrating nerves can also mediate multiple tumor biological processes via exosomes and neurotransmitters. In this review, through seminal studies establishing tumor innervation, we discuss the communication between peripheral nerves and tumor cells in the tumor microenvironment (TME), and revealed the nerve-tumor regulation mechanisms on oncogenic process, angiogenesis, lymphangiogenesis, and immunity. Finally, we discussed the promising directions of ‘old drugs newly used’ to target TME communication and clarified a new line to prevent tumor malignant capacity.

Abstract Acetaminophen (APAP)-induced liver injury (AILI) is the most frequent cause of acute liver failure; but the underlying mechanisms still remain obscure. Macrophages and endoplasmic reticulum (ER) stress play an important role in the pathogenesis of AILI. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a newly identified 18-kDa soluble protein, whose expression and secretion are stimulated by ER stress. To investigate the role of myeloid cell MANF in the pathogenesis of AILI, we assayed serum and liver samples from AILI model mice and patients with drug-induced liver injury (DILI). We demonstrated that the levels of MANF were elevated in patients with DILI and in mice with AILI. Moreover, myeloid-specific MANF knockout mice were generated and used. It was observed that a delayed liver recovery from myeloid-specific MANF gene knockout mice following APAP overdose compared to that from wild-type mice. MANF deficiency in myeloid cells resulted in increased infiltrating monocyte-derived macrophages (MoMFs) but reduced restorative Ly6Clow macrophages after APAP treatment. MANF supplementation increased restorative Ly6Clow macrophages and subsequently alleviated liver injury. Moreover, MANF could enhance IL-10 expression and phagocytosis in macrophages via p38 MAPK pathway. Altogether, MANF seems to be a critical immune modulator in promoting liver repair via reducing and reprogramming MoMFs. MANF perhaps promoted the phenotype conversion of pro-inflammatory MoMFs to pro-restorative Ly6Clow MoMFs via p38 MAPK pathway, particularly through enhancing IL-10 and phagocytosis.

Abstract Autophagy is a conserved method of quality control in which cytoplasmic contents are degraded via lysosomes. Lipophagy, a form of selective autophagy and a novel type of lipid metabolism, has recently received much attention. Lipophagy is defined as the autophagic degradation of intracellular lipid droplets (LDs). Although much remains unknown, lipophagy appears to play a significant role in many organisms, cell types, metabolic states, and diseases. It participates in the regulation of intracellular lipid storage, intracellular free lipid levels (e.g., fatty acids), and energy balance. However, it remains unclear how intracellular lipids regulate autophagy. Impaired lipophagy can cause cells to become sensitive to death stimuli and may be responsible for the onset of a variety of diseases, including nonalcoholic fatty liver disease and metabolic syndrome. Like autophagy, the role of lipophagy in cancer is poorly understood, although analysis of specific autophagy receptors has helped to expand the diversity of chemotherapeutic targets. These studies have stimulated increasing interest in the role of lipophagy in the pathogenesis and treatment of cancer and other human diseases.

Abstract Proper follicle development is very important for the production of mature oocytes, which is essential for the maintenance of female fertility. This complex biological process requires precise gene regulation. The most abundant modification of mRNA, N 6-methyladenosine (m6A), is involved in many RNA metabolism processes, including RNA splicing, translation, stability, and degradation. Here, we report that m6A plays essential roles during oocyte and follicle development. Oocyte-specific inactivation of the key m6A methyltransferase Mettl3 with Gdf9-Cre caused DNA damage accumulation in oocytes, defective follicle development, and abnormal ovulation. Mechanistically, combined RNA-seq and m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) data from oocytes revealed, that we found METTL3 targets Itsn2 for m6A modification and then enhances its stability to influence the oocytes meiosis. Taken together, our findings highlight the crucial roles of mRNA m6A modification in follicle development and coordination of RNA stabilization during oocyte growth.

Abstract Pain of the orofacial region is the primary complaint for which patients seek treatment. Of all the orofacial pain conditions, one condition that possess a significant global health problem is temporomandibular disorder (TMD). Patients with TMD typically frequently complaints of pain as a symptom. TMD can occur due to complex interplay between peripheral and central sensitization, endogenous modulatory pathways, and cortical processing. For diagnosis of TMD pain a descriptive history, clinical assessment, and imaging is needed. However, due to the complex nature of pain an additional step is needed to render a definitive TMD diagnosis. In this review we explicate the role of different biomarkers involved in painful TMD. In painful TMD conditions, the role of biomarkers is still elusive. We believe that the identification of biomarkers associated with painful TMD may stimulate researchers and clinician to understand the mechanism underlying the pathogenesis of TMD and help them in developing newer methods for the diagnosis and management of TMD. Therefore, to understand the potential relationship of biomarkers, and painful TMD we categorize the biomarkers as molecular biomarkers, neuroimaging biomarkers and sensory biomarkers. In addition, we will briefly discuss pain genetics and the role of potential microRNA (miRNA) involved in TMD pain.

Leukemia is a leading cause of cancer death. Recently, the latexin (Lxn) gene was identified as a potential tumor suppressor in several types of solid tumors and lymphoma, and Lxn expression was found to be absent or downregulated in leukemic cells. Whether Lxn functions as a tumor suppressor in leukemia and what molecular and cellular mechanisms are involved are unknown. In this study, the myeloid leukemogenic FDC-P1 cell line was used as a model system and Lxn was ectopically expressed in these cells. Using the protein pull-down assay and mass spectrometry, ribosomal protein subunit 3 (Rps3) was identified as a novel Lxn binding protein. Ectopic expression of Lxn inhibited FDC-P1 growth in vitro. More surprisingly, Lxn enhanced gamma irradiation-induced DNA damages and induced cell-cycle arrest and massive necrosis, leading to depletion of FDC-P1 cells. Mechanistically, Lxn inhibited the nuclear translocation of Rps3 upon radiation, resulting in abnormal mitotic spindle formation and chromosome instability. Rps3 knockdown increased the radiation sensitivity of FDC-P1, confirming that the mechanism of action of Lxn is mediated by Rps3 pathway. Moreover, Lxn enhanced the cytotoxicity of chemotherapeutic agent, VP-16, on FDC-P1 cells. Our study suggests that Lxn itself not only suppresses leukemic cell growth but also potentiates the cytotoxic effect of radio- and chemotherapy on cancer cells. Lxn could be a novel molecular target that improves the efficacy of anti-cancer therapy.

Asymmetric optical transmission (AOT) has been an enduring hot topic of interest in various fields, including optical communication, information processing, and so on. Particularly, the development of reciprocal micro-nanostructures achieving AOT further facilitates and accelerates the miniaturization and integration of traditional optical components. However, most of these optical components merely consider a single AOT band and transmission in a specified direction, limiting the development of their versatile functions. In this paper, we theoretically propose an all-dielectric metamaterial consisting of a nanograting and a defective multilayer photonic crystal, exhibiting multi-band and bidirectional multiplexing AOT. More specifically, the proposed metamaterial demonstrates both narrowband and wideband AOT for incidence from the nanograting to the photonic crystal, and a completely different narrowband AOT for the opposite incidence, namely, from the photonic crystal to the nanograting. These distinctive AOT spectral features are achieved by matching the diffraction effect of the nanograting with the special energy band of the defective multilayer photonic crystal. Remarkably, the device exhibits a transmittance difference of up to 0.974 and a contrast ratio of up to 0.997 (transmittance ratio of up to 673), with a transmission bandwidth of 62.7 nm for incident light with a wavelength of 624 nm illuminating from the nanograting to the defective multilayer photonic crystal. Furthermore, the bandwidth and number of transmission bands can be flexibly tuned by changing the polarization angle of the incident light, showcasing its excellent polarization multiplexing characteristics. The designed metamaterial provides an effective strategy for the realization of versatile AOT devices and is conducive to expanding the application scenarios of AOT devices., (© 2024. The Author(s).)

Diabetic nephropathy (DN) is one of the most important comorbidities of diabetic patients, which places large physiological and economic burdens on patients. Safflower yellow, a natural pigment extracted from the petals of safflower, has been put into adjuvant therapy. Databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, MEDLINE and etc. will be searched for relevant articles. A meta-analysis was carried out to assess the efficacy and safety of safflower yellow adjuvant to conventional treatment regimen using mean differences (MD) and rate ratios (RR). A cost-effectiveness analysis was also conducted based on the result of meta-analysis. Finally, 28 articles involving 2251 patients were included in meta-analysis. The results showed that compared with conventional treatment, the fasting blood-glucose (FBG) [MD = 0.40], urinary albumin ejection rate (UAER) within 24 h [MD = 48.16], serum creatinine (Scr) [MD = 9.63], blood urea nitrogen (BUN) [MD = 1.73] were significantly lower and the clinical efficacy [RR = 1.28] was more remarkable in safflower yellow adjuvant to conventional treatment group. Our analysis suggested that safflower yellow adjuvant to conventional treatment regimen not only had better clinical efficacy but more cost-effective than conventional treatment regimen., (© 2024. The Author(s).)

Alzheimer's disease (AD) is the most common cause of dementia, characterized by memory loss, cognitive decline, personality changes, and various neurological symptoms. The role of blood-brain barrier (BBB) injury, extracellular matrix (ECM) abnormalities, and oligodendrocytes (ODCs) dysfunction in AD has gained increasing attention, yet the detailed pathogenesis remains elusive. This study integrates single-cell sequencing of AD patients' cerebrovascular system with a genome-wide association analysis. It aims to elucidate the associations and potential mechanisms behind pericytes injury, ECM disorder, and ODCs dysfunction in AD pathogenesis. Finally, we identified that abnormalities in the pericyte PI3K-AKT-FOXO signaling pathway may be involved in the pathogenic process of AD. This comprehensive approach sheds new light on the complex etiology of AD and opens avenues for advanced research into its pathogenesis and therapeutic strategies., (© 2024. The Author(s).)

There is considerable uncertainty regarding the associations between various risk factors and Parkinson's Disease (PD). This study systematically screened and validated a wide range of potential PD risk factors from 502,364 participants in the UK Biobank. Baseline data for 1851 factors across 11 categories were analyzed through a phenome-wide association study (PheWAS). Polygenic risk scores (PRS) for PD were used to diagnose Parkinson's Disease and identify factors associated with PD diagnosis through PheWAS. Two-sample Mendelian randomization (MR) analysis was employed to assess causal relationships. PheWAS results revealed 267 risk factors significantly associated with PD-PRS among the 1851 factors, and of these, 27 factors showed causal evidence from MR analysis. Compelling evidence suggests that fluid intelligence score, age at first sexual intercourse, cereal intake, dried fruit intake, and average total household income before tax have emerged as newly identified risk factors for PD. Conversely, maternal smoking around birth, playing computer games, salt added to food, and time spent watching television have been identified as novel protective factors against PD. The integration of phenotypic and genomic data may help to identify risk factors and prevention targets for PD., (© 2024. The Author(s).)

Hypoxia is a common feature of lung squamous cell carcinoma (LUSC), and hypoxia-inducible factor-1 (HIF-1) overexpression is associated with poor clinical outcome in LUSC. NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) is a recently identified target of HIF-1, but its roles in LUSC remain unclear. Herein, the expression and regulatory mechanisms of NDUFA4L2 were investigated in LUSC, and the influences on LUSC cell oxidative metabolism and survival of NDUFA4L2 were determined. The potential microRNA targeting to NDUFA4L2 was identified and its roles on LUSC cell were detected. We found that NDUFA4L2 were overexpressed in LUSC tissues, and that NDUFA4L2 expression correlated with shorter overall survival. NDUFA4L2 was regulated by HIF-1α under hypoxia, and NDUFA4L2 decreased mitochondrial reactive oxygen species (mitoROS) production through inhibiting mitochondrial complex I activity in LUSC cells. NDUFA4L2 silencing effectively suppressed LUSC cell growth and enhanced apoptosis by inducing mitoROS accumulation. Additionally, NDUFA4L2 was a target for miR-183-5p, and LUSC patients with high miR-183-5p levels had better prognoses. MiR-183-5p significantly induced mitoROS production and suppressed LUSC survival through negatively regulating NDUFA4L2 in vitro and in vivo. Our results suggested that regulation of NDUFA4L2 by HIF-1α is an important mechanism promoting LUSC progression under hypoxia. NDUFA4L2 inhibition using enforced miR-183-5p expression might be an effective strategy for LUSC treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The power industry's low carbon transition is pivotal for achieving carbon reduction and sustainable development. This study uses the super epsilon-based measurement (Super-EBM) model and the Malmquist index to evaluate the power industry's low carbon transition efficiency using data from 30 provinces in China from 2010 to 2020, and utilizes the Tobit model to comprehensively analyze the factors affecting the low carbon transition of power industry. In addition, this paper examines the spatial differences in the power industry's low carbon transition efficiency as well as its distributional characteristics and dynamic evolutionary patterns. Conclusion is drawn as follows this paper analyzes the regional differences, spatial distribution characteristics and dynamic evolutionary trends of the power industry's low carbon transition. The main conclusions are as follows: (1) The power industry's low carbon transition efficiency in China shows an uptrend, with the western China region having the highest overall level of efficiency, greater fluctuations in the central China region, and more stability in the eastern China region, technological progress is a central factor in increasing total factor productivity, the efficiency of the power industry's low carbon transition is positively influenced by the electricity prices, and negatively influenced by the energy structure, environmental regulations and economic structure; (2) the Intraregional differences and hypervariable density are the main reasons sources of the overall differences in the efficiency of the power industry's low carbon transition; Intraregional differences in the eastern, central, and western China regions are decreasing year by year, but the efficiency of the power industry's low carbon transition in the western China region is still distributed in a multipolar way; (3) The dynamic evolutionary trends of the efficiency distribution of the low carbon transition in power industry is influenced by the type of spatial lag in the neighboring area. Where areas with low efficiency makes it difficult to achieve short-term leapfrog development, and areas with a cluster of high-efficiency provinces are prone to "Siphon Effect". The findings provide a theoretical basis for promoting the efficiency of the power industry's low carbon transition and coordinating the strategic adjustment of economic and environmental green development., (© 2024. The Author(s).)

Radiation-free one-stage bedside endoscopic stone removal and biliary drainage for severe acute cholangitis (SAC) caused by choledocholithiasis in intensive care unit (ICU) has not been reported. Herein, we introduce our preliminary experience of such intervention. Radiation-free bedside digital cholangioscope-assisted one-stage endoscopic stone removal and biliary drainage was performed in an urgent manner. Data on clinical outcomes and follow-up from thirty patients were retrospectively analyzed. Time interval was 7.6 ± 4.7 (2-18) h between ICU admission and endoscopic intervention, and was 35.5 ± 14.5 (5-48) h between the seizure and endoscopic intervention. A 100% technical success was achieved. Except for one mild pancreatitis, no other complication occurred. Patients showed good responses to endoscopic interventions, which were reflected by ameliorated disease severities and laboratory findings. Time lengths of ICU stay and total in-hospital stay were 8.7 ± 4.9 (2-23) days and 14.5 ± 7.4 (5-39) days, respectively. In-hospital mortality occurred in three patients. According to a 6-month follow-up, two patients died of pneumonia and acute myocardial infarction. No SAC and/or biliary stone residual occurred. The current intervention demonstrated favorable results compared to traditional endoscopic retrograde cholangiopancreatography. Our study provides a novel bedside endoscopic intervention method for SAC caused by choledocholithiasis., (© 2024. The Author(s).)

As a class of biologically active molecules with significant immunomodulatory and anti-inflammatory effects, anti-inflammatory peptides have important application value in the medical and biotechnology fields due to their unique biological functions. Research on the identification of anti-inflammatory peptides provides important theoretical foundations and practical value for a deeper understanding of the biological mechanisms of inflammation and immune regulation, as well as for the development of new drugs and biotechnological applications. Therefore, it is necessary to develop more advanced computational models for identifying anti-inflammatory peptides. In this study, we propose a deep learning model named DAC-AIPs based on variational autoencoder and contrastive learning for accurate identification of anti-inflammatory peptides. In the sequence encoding part, the incorporation of multi-hot encoding helps capture richer sequence information. The autoencoder, composed of convolutional layers and linear layers, can learn latent features and reconstruct features, with variational inference enhancing the representation capability of latent features. Additionally, the introduction of contrastive learning aims to improve the model's classification ability. Through cross-validation and independent dataset testing experiments, DAC-AIPs achieves superior performance compared to existing state-of-the-art models. In cross-validation, the classification accuracy of DAC-AIPs reached around 88%, which is 7% higher than previous models. Furthermore, various ablation experiments and interpretability experiments validate the effectiveness of DAC-AIPs. Finally, a user-friendly online predictor is designed to enhance the practicality of the model, and the server is freely accessible at http://dac-aips.online ., (© 2024. The Author(s).)

Precise forecasting of satellite clock bias is crucial for ensuring service quality and enhancing the efficiency of real-time precise point positioning (PPP).The grey model with many benefits is an excellent choice for predicting real-time clock bias. However, the absolute prediction error of a small number of satellites is very high in actual forecasting process. In order to address this issue, a non-homogeneous white exponential law grey model has been constructed specifically for predicting clock bias sequences with non-homogeneous class ratio approximating constants. Considering that any model is difficult to apply to different kinds of satellite clocks and clock bias signals, an adaptive selection strategy for forecast model is proposed to ensure more excellent prediction accuracy. Afterwards, a prediction scenario based on the observed products of the BeiDou satellite navigation system (BDS) is created to demonstrate the effectiveness of the approach described in this article. The outcomes of the method are then compared with those of a single grey model and the ultra-rapid predicted products. The outcomes demonstrate that this strategy's prediction accuracy is less than 1 ns/day and that its prediction uncertainty is much decreased, which may improve data selection for real-time applications like real-time kinematics (RTK) and PPP., (© 2024. The Author(s).)

Hot-carrier transistors are a class of devices that leverage the excess kinetic energy of carriers. Unlike regular transistors, which rely on steady-state carrier transport, hot-carrier transistors modulate carriers to high-energy states, resulting in enhanced device speed and functionality. These characteristics are essential for applications that demand rapid switching and high-frequency operations, such as advanced telecommunications and cutting-edge computing technologies 1-5 . However, the traditional mechanisms of hot-carrier generation are either carrier injection 6-11 or acceleration 12,13 , which limit device performance in terms of power consumption and negative differential resistance 14-17 . Mixed-dimensional devices, which combine bulk and low-dimensional materials, can offer different mechanisms for hot-carrier generation by leveraging the diverse potential barriers formed by energy-band combinations 18-21 . Here we report a hot-emitter transistor based on double mixed-dimensional graphene/germanium Schottky junctions that uses stimulated emission of heated carriers to achieve a subthreshold swing lower than 1 millivolt per decade beyond the Boltzmann limit and a negative differential resistance with a peak-to-valley current ratio greater than 100 at room temperature. Multi-valued logic with a high inverter gain and reconfigurable logic states are further demonstrated. This work reports a multifunctional hot-emitter transistor with significant potential for low-power and negative-differential-resistance applications, marking a promising advancement for the post-Moore era., (© 2024. The Author(s).)

The position of the internal os of the cervix reported in the literature was inconsistent on MRI images. Additionally, the practical impactful data influencing the internal os located by MRI is limited. We aimed to confirm the position of the internal os of the cervix on MRI images, and the influencing factors locating the the internal os by MRI. A single-center retrospective study was conducted. Data from 175 patients who underwent total hysterectomy for stage I endometrial cancer were collected. The internal os of the cervix is positioned as the starting point for measuring the length of the cervix on MRI images. On dynamic contrast-enhanced MRI (DCE-MRI), the section formed by the enhancement difference between the uterus and cervix, and on T2-weighted imaging(T2WI), the section formed by the physiological curvature of the uterus and the low signal intensity of the cervical stroma were used as starting points. The results showed no statistically significant difference compared with the removed uterus specimens (p = 0.208, p = 0.571, p = 0.804). A history of cesarean section(p < 0.001), irregular vaginal bleeding for more than three months(p < 0.001), cervical adenomyosis(p = 0.043), and premenopause(p = 0.001) were not conducive to locating the internal os of the cervix by MRI. Our findings provide valuable information and confirm the position of the internal os of the cervix on MRI images, and the several important infuencing factors. We hope that some patients will benefit from our study., (© 2024. The Author(s).)

The CRISPR/Cas9 system has shown great potential for treating human genetic diseases through gene therapy. However, there are concerns about the safety of this system, specifically related to the use of guide-free Cas9. Previous studies have shown that guide-free Cas9 can induce genomic instability in vitro. However, the in vivo safety risks associated with guide-free Cas9 have not been evaluated, which is necessary for the development of gene therapy in clinical settings. In this study, we used doxycycline-inducible Cas9-expressing pigs to evaluate the safety risks of guide-free Cas9 in vivo. Our findings demonstrated that expression of guide-free Cas9 could induce genomic damages and transcriptome changes in vivo. The severity of the genomic damages and transcriptome changes were correlate with the expression levels of Cas9 protein. Moreover, prolonged expression of Cas9 in pigs led to abnormal phenotypes, including a significant decrease in body weight, which may be attributable to genomic damage-induced nutritional absorption and metabolic dysfunction. Furthermore, we observed an increase in whole-genome and tumor driver gene mutations in pigs with long-term Cas9 expression, raising the risk of tumor occurrence. Our in vivo evaluation of guide-free Cas9 in pigs highlights the necessity of considering and monitoring the detrimental effects of Cas9 alone as genome editing via the CRISPR/Cas9 system is implemented in clinical gene therapy. This research emphasizes the importance of further study and implementation of safety measures to ensure the successful and safe application of the CRISPR/Cas9 system in clinical practice., (© 2024. The Author(s).)

The role of tumor-resident microbiota in modulating tumor immunity remains unclear. Here, we discovered an abundance of intra-tumoral bacteria, such us E.coli, residing and resulting in Colorectal cancer liver metastasis (CRLM). E.coli enhanced lactate production, which mediated M2 macrophage polarization by suppressing nuclear factor-κB -gene binding (NF-κB) signaling through retinoic acid-inducible gene 1 (RIG-I) lactylation. Lactylation of RIG-I suppressed recruitment of NF-κB to the Nlrp3 promoter in macrophages, thereby reducing its transcription. This loss of Nlrp3 affected the immunosuppressive activities of regulatory T cells (Tregs) and the antitumor activities of and CD8 + T cells. Small-molecule compound screening identified a RIG-I lactylation inhibitor that suppressed M2 polarization and sensitized CRLM to 5-fluorouracil (5-FU). Our findings suggest that tumor-resident microbiota may be a potential target for preventing and treating CRLM., (© 2024. The Author(s).)

Eucommia ulmoides is a traditional Chinese herbal medicine, with pharmacological effects such as lowering blood pressure and enhancing immune function. The effects of dietary Eucommia ulmoides polysaccharide (EUP) on immune function and meat quality were studied in Songliao Black Pigs. Blood lymphocyte counts and percentage, concentrations of serum total protein and of albumin increased, whereas those of urea nitrogen and triglyceride decreased. White blood cell and lymphocyte counts, and serum IgA, IgE, IgG2 a and IFN-γ increased. Average daily weight gain, slaughter weight, lean meat rate and cooked meat rate increased, whereas pH 24 , feed-weight ratio, fat rate, yellowness (b # ) and centrifugal dehydration rate decreased. Transcriptome sequencing of longissimus dorsi muscle detected 32 differentially expressed genes (DEGs), of which 26 were up-regulated and 6 down-regulated. A total of 19 genes were differentially expressed in the four groups, 18 of which were up-regulated. The DEGs included ADAMTS4, PER1, STAC, SERPINE1, FASN, THRSP, SP7 and KRT80 and the protein interaction network showed 20 up-regulated nodes, three down-regulated nodes and 14 DEGs. GO functional annotation and enrichment analysis showed that 34 items were significantly enriched, including transferase activity, actin binding, acetyl coenzyme A, acyl coenzyme A metabolism, adipose tissue development and acyl glycerol homeostasis. KEGG pathway analysis showed that the AMPK and PPAR signaling pathways were enriched. Dietary Eucommia polysaccharide enhanced immune function in Songliao Black Pigs, improved growth and carcass performance, increased the expression of genes related to meat quality traits and improved meat quality., (© 2024. The Author(s).)

The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health., (© 2024. The Author(s).)

Triple-negative breast cancer (TNBC) is an exceptionally aggressive subtype of breast cancer. Despite the recognized interplay between tumors and tumor-associated macrophages in fostering drug resistance and disease progression, the precise mechanisms leading these interactions remain elusive. Our study revealed that the upregulation of collagen type V alpha 1 (COL5A1) in TNBC tissues, particularly in chemoresistant samples, was closely linked to an unfavorable prognosis. Functional assays unequivocally demonstrated that COL5A1 played a pivotal role in fueling cancer growth, metastasis, and resistance to doxorubicin, both in vitro and in vivo. Furthermore, we found that the cytokine IL-6, produced by COL5A1-overexpressing TNBC cells actively promoted M2 macrophage polarization. In turn, TGFβ from M2 macrophages drived TNBC doxorubicin resistance through the TGFβ/Smad3/COL5A1 signaling pathway, establishing a feedback loop between TNBC cells and macrophages. Mechanistically, COL5A1 interacted with TGM2, inhibiting its K48-linked ubiquitination-mediated degradation, thereby enhancing chemoresistance and increasing IL-6 secretion. In summary, our findings underscored the significant contribution of COL5A1 upregulation to TNBC progression and chemoresistance, highlighting its potential as a diagnostic and therapeutic biomarker for TNBC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The prognosis for patients with colorectal cancer (CRC) remains worse than expected due to metastasis, recurrence, and resistance to chemotherapy. Colorectal cancer stem cells (CRCSCs) play a vital role in tumor metastasis, recurrence, and chemotherapy resistance. However, there are currently no prognostic markers based on CRCSCs-related genes available for clinical use. In this study, single-cell transcriptome sequencing was employed to distinguish cancer stem cells (CSCs) in the CRC microenvironment and analyze their properties at the single-cell level. Subsequently, data from TCGA and GEO databases were utilized to develop a prognostic risk model for CRCSCs-related genes and validate its diagnostic performance. Additionally, functional enrichment, immune response, and chemotherapeutic drug sensitivity of the relevant genes in the risk model were investigated. Lastly, the key gene RPS17 in the risk model was identified as a potential prognostic marker and therapeutic target for further comprehensive studies. Our findings provide new insights into the prognostic treatment of CRC and offer novel perspectives for a systematic and comprehensive understanding of CRC development., (© 2024. The Author(s).)

Peripheral CD8 + T cell number is tightly controlled but the precise molecular mechanism regulating this process is still not fully understood. In this study, we found that epilepsy patients with loss of function mutation of DEPDC5 had reduced peripheral CD8 + T cells, and DEPDC5 expression positively correlated with tumor-infiltrating CD8 + T cells as well as overall cancer patient survival, indicating that DEPDC5 may control peripheral CD8 + T cell homeostasis. Significantly, mice with T cell-specific Depdc5 deletion also had reduced peripheral CD8 + T cells and impaired anti-tumor immunity. Mechanistically, Depdc5-deficient CD8 + T cells produced high levels of xanthine oxidase and lipid ROS due to hyper-mTORC1-induced expression of ATF4, leading to spontaneous ferroptosis. Together, our study links DEPDC5-mediated mTORC1 signaling with CD8 + T cell protection from ferroptosis, thereby revealing a novel strategy for enhancing anti-tumor immunity via suppression of ferroptosis., (© 2024. The Author(s).)

Necroptosis is a lytic form of cell death that is mediated by the kinase RIPK3 and the pseudokinase MLKL when caspase-8 is inhibited downstream of death receptors, toll-like receptor 3 (TLR3), TLR4, and the intracellular Z-form nucleic acid sensor ZBP1. Oligomerization and activation of RIPK3 is driven by interactions with the kinase RIPK1, the TLR adaptor TRIF, or ZBP1. In this study, we use immunohistochemistry (IHC) and in situ hybridization (ISH) assays to generate a tissue atlas characterizing RIPK1, RIPK3, Mlkl, and ZBP1 expression in mouse tissues. RIPK1, RIPK3, and Mlkl were co-expressed in most immune cell populations, endothelial cells, and many barrier epithelia. ZBP1 was expressed in many immune populations, but had more variable expression in epithelia compared to RIPK1, RIPK3, and Mlkl. Intriguingly, expression of ZBP1 was elevated in Casp8 -/- Tnfr1 -/- embryos prior to their succumbing to aberrant necroptosis around embryonic day 15 (E15). ZBP1 contributed to this embryonic lethality because rare Casp8 -/- Tnfr1 -/- Zbp1 -/- mice survived until after birth. Necroptosis mediated by TRIF contributed to the demise of Casp8 -/- Tnfr1 -/- Zbp1 -/- pups in the perinatal period. Of note, Casp8 -/- Tnfr1 -/- Trif -/- Zbp1 -/- mice exhibited autoinflammation and morbidity, typically within 5-7 weeks of being born, which is not seen in Casp8 -/- Ripk1 -/- Trif -/- Zbp1 -/- , Casp8 -/- Ripk3 -/- , or Casp8 -/- Mlkl -/- mice. Therefore, after birth, loss of caspase-8 probably unleashes RIPK1-dependent necroptosis driven by death receptors other than TNFR1., (© 2024. The Author(s).)

Thrombin generation (TG) and fibrin clot formation represent the central process of blood coagulation. Up to 95% of thrombin is considered to be generated after the clot is formed. However, this was not investigated in depth. In this study, we conducted a quantitative analysis of the Thrombin at Clot Time (TCT) parameter in 5758 simultaneously recorded TG and clot formation assays using frozen plasma samples from commercial sources under various conditions of activation. These samples were supplemented with clotting factor concentrates, procoagulant lipid vesicles and a fluorogenic substrate and triggered with tissue factor (TF). We found that TCT is often close to a 10% of thrombin peak height (TPH) yet it can be larger or smaller depending on whether the sample has low or high TPH value. In general, the samples with high TPH are associated with elevated TCT. TCT appeared more sensitive to some procoagulant phenotypes than other commonly used parameters such as clotting time, TPH or Thrombin Production Rate (TPR). In a minority of cases, TCT were not predicted from TG parameters. For example, elevated TCT (above 15% of TPH) was associated with either very low or very high TPR values. We conclude that clotting and TG assays may provide complementary information about the plasma sample, and that the TCT parameter may serve as an additional marker for the procoagulant potential in plasma sample., (© 2024. The Author(s).)

Sexual dysfunction is common in males with chronic kidney disease (CKD), but yet the prevalence and specific relationship between CKD and sexual dysfunction, especially premature ejaculation (PE), remain to be investigated in China; This study aims to examine the prevalence and association between CKD and sexual dysfunction in male patients in China; In this cross-sectional, non-interventional, observational study conducted at a single center. 72 male patients with CKD were enrolled. Data collection included socio-demographic information, assessments via the 5-item version of the International Index of Erectile Function (IIEF-5), the Chinese version of the Premature Ejaculation Diagnostic Tool, the Patient Health Quentionnnaire-9 and the General Anxiety Disorder-7. Data analysis was performed using R version 3.5.2 and SPSS software version 25.0; Among the 72 CKD patients, 56.9% experienced erectile dysfunction and 29.2% had PE. Various factors including estimated Glomerular Filtration Rate, Albumin-to-Creatinine Ratio, psychological aspects, medication use were found to be associated with sexual dysfunction in these CKD patients; Sexual dysfunction is prevalent in males with CKD and is, influenced by multiple factors. It is important for clinicians to focus on sexual dysfunction in this patient group and further investigate its underlying mechanisms., (© 2024. The Author(s).)

The current challenge in effectively treating atrial fibrillation (AF) stems from a limited understanding of the intricate structure of the human atria. The objective and quantitative interpretation of the right atrium (RA) in late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) scans relies heavily on its precise segmentation. Leveraging the potential of artificial intelligence (AI) for RA segmentation presents a promising solution. However, the successful implementation of AI in this context necessitates access to a substantial volume of annotated LGE-MRI images for model training. In this paper, we present a comprehensive 3D cardiac dataset comprising 50 high-resolution LGE-MRI scans, each meticulously annotated at the pixel level. The annotation process underwent rigorous standardization through crowdsourcing among a panel of medical experts, ensuring the accuracy and consistency of the annotations. Our dataset represents a significant contribution to the field, providing a valuable resource for advancing RA segmentation methods., (© 2024. The Author(s).)

Analyzing the stability of footings is a significant step in civil/geotechnical engineering projects. In this work, two novel predictive tools are suggested based on an artificial neural network (ANN) to analyze the bearing capacity of a footing installed on a two-layered soil mass. To this end, backtracking search algorithm (BSA) and equilibrium optimizer (EO) are employed to train the ANN for approximating the stability value (SV) of the system. After executing a set of finite element analyses, the settlement values lower/higher than 5 cm are considered to indicate the stability/failure of the system. The results demonstrated the efficiency of these algorithms in fulfilling the assigned task. In detail, the training error of the ANN (in terms of root mean square error-RMSE)) dropped from 0.3585 to 0.3165 (11.72%) and 0.2959 (17.46%) by applying the BSA and EO, respectively. Moreover, the prediction accuracy of the ANN climbed from 93.7 to 94.3% and 94.1% (in terms of area under the receiving operating characteristics curve-AUROC). A comparison between the elite complexities of these algorithms showed that the EO enjoys a larger accuracy, while BSA is a more time-effective optimizer. Lastly, an explicit mathematical formula is derived from the EO-ANN model to be conveniently used in predicting the SV., (© 2024. The Author(s).)

Concrete-filled steel tube columns (CFSTCs) are important elements in the construction sector and predictive analysis of their behavior is essential. Recent works have revealed the potential of metaheuristic-assisted approximators for this purpose. The main idea of this paper, therefore, is to introduce a novel integrative model for appraising the axial compression capacity (P u ) of CFSTCs. The proposed model represents an artificial neural network (ANN) supervised by satin bowerbird optimizer (SBO). In other words, this metaheuristic algorithm trains the ANN optimally to find the best contribution of input parameters to the P u . In this sense, column length and the compressive strength of concrete, as well as the characteristics of the steel tube (i.e., diameter, thickness, yield stress, and ultimate stress), are considered input data. The prediction results are compared to five ANNs supervised by backtracking search algorithm (BSA), earthworm optimization algorithm (EWA), social spider algorithm (SOSA), salp swarm algorithm (SSA), and wind-driven optimization. Evaluating various accuracy indicators showed that the proposed model surpassed all of them in both learning and reproducing the P u pattern. The obtained values of mean absolute percentage error of the SBO-ANN was 2.3082% versus 4.3821%, 17.4724%, 15.7898%, 4.2317%, and 3.6884% for the BSA-ANN, EWA-ANN, SOSA-ANN, SSA-ANN and WDA-ANN, respectively. The higher accuracy of the SBO-ANN against several hybrid models from earlier literature was also deduced. Moreover, the outcomes of principal component analysis on the dataset showed that the yield stress, diameter, and ultimate stress of the steel tube are the three most important factors in P u prediction. A predictive formula is finally derived from the optimized SBO-ANN by extracting and organizing the weights and biases of the ANN. Owing to the accurate estimation shown by this model, the derived formula can reliably predict the P u of concrete-filled steel tube columns., (© 2024. The Author(s).)

Low-energy and efficient coal gangue sorting is crucial for environmental protection. Multispectral imaging (MSI) has emerged as a promising technology in this domain. This work addresses the challenge of low resolution and poor recognition performance in underground MSI equipment. We propose an attention-based multi-level residual network (ANIMR) within a super-resolution reconstruction model (ANIMR-GAN) inspired by CycleGAN. This model incorporates improvements to the discriminator and loss function. We trained the model on 600 coal and gangue MSI samples and validated it on an independent set of 120 samples. The ANIMR-GAN, combined with a random forest classifier, achieved a maximum accuracy of 97.78% and an average accuracy of 93.72%. Furthermore, the study identifies the 959.37 nm band as optimal for coal and gangue classification. Compared to existing super-resolution methods, ANIMR-GAN offers advantages, paving the way for intelligent and efficient coal gangue sorting, ultimately promoting advancements in sustainable mineral processing., (© 2024. The Author(s).)

Vicenistatin (1) is a 20-membered polyketide macrocyclic antibiotic with potent antimicrobial and cytotoxic activities. In this study, to further explore the potential of 1 as candidates of antibacterial drug development, 4'-N-demethyl vicenistatin (2), a secondary metabolite obtained from the ∆vicG mutant strain of Monodonata labio-associated Streptomyces parvus SCSIO Mla-L010, was utilized as a starting material for modifications of 4'-amino group of vicenistatin. Six new vicenistatin derivatives (3-8) were semi-synthesized through a concise route of amino modification with various aliphatic and aromatic aldehydes. Our study reveals that the bioactivity of vicenistatin is closely related to amino modification in sugar moiety, which results from the length of alkyl side chain as well as the presence of electron withdrawing/denoting group on the benzene ring. Importantly, compounds 4 with a butyl group and 8 with a 3,5-dihydroxyl-benzyl group at 4'-amino group, respectively, exhibited good antimicrobial activities, with MIC values spanning 0.5-4 μg ml -1 to Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Micrococcus luteus and Bacillus subtilis, with low cytotoxicity. This research promotes the further exploration of structure-activity relationships of vicenistatin and provides new vicenistatin derivatives for development of future anti-infectious agents with reduced cytotoxicity., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)