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Abstract To develop a simple scoring system based on baseline inflammatory and nutritional markers to predict the long-term prognosis of patients with nasopharyngeal carcinoma (NPC). Conducted a retrospective analysis of clinical data from 1024 newly diagnosed non-metastatic NPC patients. A total of 15 pre-treatment inflammatory and nutritional markers were collected as candidate variables. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff points for each parameter. Survival analysis was performed using Kaplan–Meier method and Cox regression analysis. Besides, the Inflammation Nutrition Risk Score (INRS) was calculated for each patient by assigning each independent prognostic factor a score of 1. Multivariate Cox regression analysis showed that serum albumin (ALB), systemic immune-inflammation index, and monocyte count (M) were independent prognostic factors for OS (P

Arming at the coexistence dilemma of inventory overhang and shortage of different maintenance equipment supply nodes, a steady-state coefficient of a supply node has been described with which contains inventory level, the support degree between nodes each other, the demand status of the area guaranteed by the node and the cost of risk when the demand cannot be met. The steady-state coefficient of the inventory network was calculated on the base of all of support nodes. The active adjustment is carried out flowing the corresponding algorithm according to the gap between the steady-state coefficient and the threshold which has been set before. The scientific, automatic and intelligent level of equipment adjustment can be greatly improved, consequently the success rate of maintenance support is improved if the passive stock adjustment is combined because of out of stock at the same time.

Developing practical microstructural solutions that simultaneously enable excellent corrosion resistance and mechanical properties in Al-Si-Cu-based alloys has been increasingly in demand. In this study, we attempt to tailor the microstructural evolution to manipulate the mechanical performance and corrosion resistance of Al-7Si-3Cu-(0.4 Mg)-(0.5Ge) alloys fabricated by GPa-level pressure combined with solution and/or aging treatments. It was found that as the solidification pressure increased, the dendritic growth tendency of the α-Al phase became less pronounced, and the modification of eutectic Si became increasingly significant. Complete solid solution alloys were even achieved under 6 GPa. The corresponding kinetic and thermodynamic mechanisms of pressure-induced microstructural evolution were explored in detail. Upon aging treatment, dense irregular Si precipitates emerged from the supersaturated matrix in Al-7Si-3Cu alloys solidified at 5 GPa and 6 GPa, while denser and finer Si precipitates growing along the 〈100〉Al directions dominated the matrix of Al-7Si-3Cu-0.4 Mg-0.5Ge alloys, which resulted in considerable enhancement of mechanical properties. The electrochemical corrosion behavior was evaluated in the as-cast and heat-treated conditions. The underlying corrosion mechanisms were discussed in terms of pressure, supersaturated solutes and precipitates. These results reveal the feasibility of designing high-strength and corrosion-resistant Al-Si-Cu series alloys via the manipulation of pressure and heat treatment.

The global outbreak of Mpox, caused by the monkeypox virus (MPXV), has attracted international attention and become another major infectious disease event after COVID-19. The mRNA cap N7 methyltransferase (RNMT) of MPXV methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs and plays a vital role in evading host antiviral immunity. MPXV RNMT is composed of the large subunit E1 and the small subunit E12. How E1 and E12 of MPXV assembly remains unclear. Here, we report the crystal structures of E12, the MTase domain of E1 with E12 (E1CTD-E12) complex, and the E1CTD-E12-SAM ternary complex, revealing the detailed conformations of critical residues and the structural changes upon E12 binding to E1. Functional studies suggest that E1CTD N-terminal extension (Asp545-Arg562) and the small subunit E12 play an essential role in the binding process of SAM. Structural comparison of the AlphaFold2-predicted E1, E1CTD-E12 complex, and the homologous D1-D12 complex of vaccinia virus (VACV) indicates an allosteric activating effect of E1 in MPXV. Our findings provide the structural basis for the MTase activity stimulation of the E1-E12 complex and suggest a potential interface for screening the anti-poxvirus inhibitors.

IntroductionThis study aims to investigate whether exercise adherence and positive mental character significantly affect subjective well-being among Chinese college students during the COVID-19 pandemic and whether positive mental character plays a mediating role.MethodsThe study employed questionnaires, including the Exercise Adherence Scale, the Positive Mental Character Scale, and the Subjective Well-Being Scale, which were administered to students across seven universities in Henan Province, China. A total of 1,001 participants were analyzed in the final sample. Data were analyzed using SPSS 21.0 for descriptive statistics, independent samples T-test, correlation, and regression analyses. Furthermore, structural equation model with AMOS was conducted to examine the potential mediating effect of positive mental characteristics on the relationship between exercise adherence and subjective well-being.ResultsThe results indicated significant differences in exercise adherence, positive mental character, and subjective well-being between male and female participants, with males scoring higher in all three domains. Among Chinese university students during the COVID-19 pandemic, there was a significant correlation among exercise adherence, positive mental character, and subjective well-being. Exercise adherence was found to have a significant and positive impact on both positive mental character and subjective well-being. Additionally, it was found that positive mental character had a significant positive association with subjective well-being. The mediating role of positive mental character in the relationship between exercise adherence and subjective well-being was partially supported.DiscussionExercise adherence among Chinese college students had a significant positive association on both positive mental character and subjective well-being throughout the COVID-19 pandemic. The exercise adherence can directly or indirectly enhance subjective well-being through its association with positive mental character. Therefore, positive mental and subjective well-being can be enhanced by consistent physical activity even during a pandemic.

This paper uses panel data of 260 prefecture-level cities from 2000 to 2019 to explore spatial characteristics such as spatiotemporal divergence and dynamic convergence based on measuring the level of human capital misallocation in Chinese cities and empirically tests the green development effect of human capital misallocation. The study finds that: ① the human capital misallocation levels of the country and the eight major urban agglomerations show a fluctuating downward trend. ② Divergences in human capital misallocation continue to narrow across the country and urban agglomerations, and the difference between inter-urban agglomerations is the primary source of regional difference. ③ The YRD, PRD, MYR, HC, and CP have significant σ-convergence characteristics of human capital misallocation. Meanwhile, the country and each urban agglomeration show significant spatial absolute β-convergence and conditional β-convergence trends. ④ Human capital misallocation significantly negatively affects green economic efficiency, inhibiting green economy efficiency. Therefore, in the future, it is necessary to improve the match between regional industrial structure and human capital allocation through a combination of targeted policy guidance and market mechanisms tailored to local conditions to enhance the efficiency of the green economy. The significance of the study lies in accelerating the accumulation of human capital while realizing the appropriate matching of human capital, releasing the human capital dividend to the maximum extent, and boosting the structural reform of the labor market to realize the transformation of the green economy.

IntroductionViral infections have been implicated as a risk factor for laryngeal cancer. Given the possible effects of Corona virus disease 2019 (COVID-19) on the laryngeal tissue, we investigated the causal link between COVID-19 and laryngeal cancer using a two-sample Mendelian randomization (MR) approach.MethodsWe utilized genetic data from the 5th Genome-wide association studies (GWAS) edition of the COVID-19 Host Genetics Initiative (published on January 18, 2021) and a large-scale laryngeal cancer GWAS comprising 180 cases and 218,612 controls of European ancestry. We applied inverse variance weighting, MR Egger, and weighted median methods to infer causality. We performed sensitivity analysis using the “leave-one-out” method to verify robustness.ResultsWe found no evidence of a causal association between gene-predicted COVID-19 and laryngeal cancer [Odds ratio (OR)=0.24 (95% Confidence intervals (CI), 0.05–1.26), P=0.09]. However, we observed significant inverse associations between gene-predicted COVID-19 hospitalization [OR=0.51 (95% CI, 0.28–0.95), P=0.03] and severe patients [OR=0.62 (95% CI, 0.43–0.90), P=0.01] and laryngeal cancer. Notably, the study detected important genetic variants, such as rs13050728, that modulate the expression of interferon alpha receptor 2 (IFNAR2), indicating possible roles for immune response pathways in both COVID-19 and cancer.DiscussionThis study reveals a potential interaction between COVID-19 severity, genetic factors, and laryngeal cancer, underscoring the importance of investigating the immune response mechanisms in both conditions. These findings contribute to the understanding of the complex interactions between COVID-19 and laryngeal cancer and may guide future research on the role of immune response, particularly involving IFNAR2.

Abstract Mycoplasma pneumoniae pneumonia (MPP) often overlaps with the clinical manifestations and chest imaging manifestations of other types of community-acquired pneumonia (CAP). We retrospectively analyzed the clinical and imaging data of a group of patients with CAP, summarized their clinical and imaging characteristics, and discussed the diagnostic significance of their certain HRCT findings. The HRCT findings of CAP researched in our study included tree-in-bud sign (TIB), ground-glass opacity (GGO), tree fog sign (TIB + GGO), bronchial wall thickening, air-bronchogram, pleural effusion and cavity. The HRCT findings of all cases were analyzed. Among the 200 cases of MPP, 174 cases showed the TIB, 193 showed the GGO, 175 showed the tree fog sign, 181 lacked air-bronchogram. In case taking the tree fog sign and lack of air-bronchogram simultaneously as an index to distinguish MPP from OCAP, the sensitivity was 87.5%, the specificity was 97.5%, the accuracy was 92.5%. This study showed that that specific HRCT findings could be used to distinguish MPP from OCAP. The combined HRCT findings including the tree fog sign and lacked air-bronchogram simultaneously would contribute to a more accurate diagnosis of MPP.

Urban green spaces (UGSs) provide important support for the health of urban residents and the realization of sustainable urban development. However, the spatiotemporal pattern of urban resident exposure to UGSs in cities is unclear, especially at the national scale in China. Based on the annual 30 m resolution Normalized Difference Vegetation Index (NDVI) data of the Landsat satellite, we quantitatively analyzed the change in UGS coverage from 2000 to 2020 for 320 cities in China and combined it with population data to understand the changing patterns of urban population exposure to different UGS coverage. The results indicated that the average UGS coverage decreased from 63% to 44% from 2000 to 2020 in China, which could be divided into two stages: a rapid decline phase (2000–2014) and a progressive decline phase (2015–2020). Geographically, UGS coverage declined faster in southwestern and eastern cities than in other regions, particularly in medium-sized cities. We also found that urban pixel-based areas in cities with the highest UGS coverage (80–100%) decreased rapidly, and the proportion of the urban population exposed to the highest UGS coverage also declined significantly from 2000 to 2020. Urban pixel-based areas with low UGS coverage (20–40%) continued to expand, and there was a rapid increase in the proportion of the urban population exposed to low UGS coverage, with an increase of 146 million people from 2000 to 2020. The expansion of impervious surfaces had the most significant effect on the change in UGS coverage during different periods (2000–2020, 2000–2014, and 2015–2020). Natural factors such as precipitation, surface maximum temperature, and soil moisture also affected UGS coverage change. These findings provide insights into the impact of urbanization on the natural environment of cities, availability of UGS for residents, and sustainable urban development under rapid urbanization.

It is essential to determine the occurrence of emerging organic contaminants (EOCs), such as pharmaceuticals and personal care products (PPCPs), in the ambient environment to address growing public concerns. However, such analysis is quite challenging due to the low trace level of such contaminants in water, which therefore requires several litres of water samples. In this study, a large volume solid phase extraction (LV-SPE) device was developed and evaluated for its performance in monitoring PPCPs as an example. Relatively good recoveries and reproducibility were obtained under specific operating conditions: a water sample volume of no more than 20 L, a flow rate not exceeding 120 mL/min, and a methanol elution volume of at least 30 mL. In addition, the results from the onsite enrichment approach using LV-SPE were compared with those from the conventional approach using a standard SPE device in the laboratory for real groundwater samples. Among the eight selected PPCPs (nalidixic acid, carbamazepine, bezafibrate, clofibric acid, sulfadiazine, sulfamethoxypyridazine, sulfamethazine and sulfamonomethoxine), LV-SPE approach detected more target compounds. While the detected concentrations were generally comparable, slightly higher concentrations were observed for carbamazepine, clofibric acid, sulfadiazine and sulfamethazine using the LV-SPE method. The developed LV-SPE device provides an alternative approach for trace analysis of PPCPs and may also be applicable for other emerging organic contaminants.

Summary: The molecular mechanism of ibrutinib-induced atrial fibrillation (AF) remains unclear. We here demonstrate that treating rats with ibrutinib for 4 weeks resulted in the development of inducible AF, left atrial enlargement, atrial fibrosis, and downregulation of connexin expression, which were associated with C-terminal Src kinase (CSK) inhibition and Src activation. Ibrutinib upregulated angiotensin-converting enzyme (ACE) protein expression in human pulmonary microvascular endothelial cells (HPMECs) by inhibiting the PI3K-AKT pathway, subsequently increasing circulating angiotensin II (Ang II) levels. However, the expression of ACE and Ang II in the left atria was not affected. Importantly, we observed that perindopril significantly mitigated ibrutinib-induced left atrial remodeling and AF promotion by inhibiting the activation of the ACE and its downstream CSK-Src signaling pathway. These findings indicate that the Ibrutinib-induced activation of the ACE contributes to AF development and could serve as a novel target for potential prevention strategies.

Auxiliary information sources, a subset of target recognition data sources, play a significant role in target recognition. The reliability and importance of these sources can vary, thereby affecting the effectiveness of the data provided. Consequently, it is essential to integrate these auxiliary information sources prior to their utilization for identification. The Dempster-Shafer (DS) evidence theory, a well-established data-fusion method, offers distinct advantages in handling and combining uncertain information. In cases where conflicting evidence sources and minimal disparities in fundamental probability allocation are present, the implementation of DS evidence theory may demonstrate deficiencies. To address these concerns, this study refined DS evidence theory by introducing the notion of invalid evidence sources and determining the similarity weight of evidence sources through the Pearson correlation coefficient, reflecting the credibility of the evidence. The significance of evidence is characterized by entropy weights, taking into account the uncertainty of the evidence source. The proposed asymptotic adjustment compression function adjusts the basic probability allocation of evidence sources using comprehensive weights, leading to symmetric compression and control of the influence of evidence sources in data fusion. The simulation results and their application in ship target recognition demonstrate that the proposed method successfully incorporates basic probability allocation calculations for ship targets in various environments. In addition, the method effectively integrates data from multiple auxiliary information sources to produce accurate fusion results within an acceptable margin of error, thus validating its efficacy. The superiority of the proposed method is proved by comparing it with other methods that use the calculated weights to weight the basic probability allocation of the evidence sources.

In order to adapt to the current rapid development of aerospace，automotive，and high-end equipment manufacturing industries，using graphene quantum dots (GQDs) with unique properties as the second phase additive，Ni-based nanocomposite coatings were prepared by supercritical pulse electrodeposition technology.The effect of pulse frequency on the microstructure，corrosion resistance，microhardness，wear resistance and other properties of composite coatings under supercritical conditions was investigated.Results showed that when the pulse frequency was 2 000 Hz under supercritical conditions，the microstructure of the prepared coating was densified and uniform，with better sphericity.XRD results showed that supercritical conditions could change the preferred orientation of crystallization and the appropriate pulse frequency could refine the coating grains and reduce the grain size.At a pulse frequency of 2 000 Hz under supercritical conditions，the properties of the prepared coating were more excellent.Electrochemical experiments showed that it had the largest capacitive arc radius，the highest self-corrosion potential，the lowest corrosion current density，and the largest capacitive modulus，so the coating had the most excellent corrosion resistance.The coating prepared at 2 000 Hz pulse frequency had the highest microhardness，reaching 835.4 HV2 N，and had the best wear resistance with a wear scar cross-sectional area of the coating of 1 582 μm2.The microhardness and wear scar cross-sectional area were 126%，107%，121%and 134%，and 47.6%，57.1%，71.5%and 44.3%of the coatings prepared with pulse frequencies of 100，1 000，3 000 Hz and under room temperature and pressure，respectively.Under supercritical conditions，the graphene quantum dot composite coating prepared at a pulse frequency of 2 000 Hz had excellent corrosion resistance and wear resistance.

Abstract Purpose Circular RNAs (circRNAs) are recently identified as a class of non-coding RNAs that participate in the incidence of acute myocardial infarction (AMI). However, circRNAs expression pattern in obstructive sleep apnea (OSA) with AMI remains unknown. The aim was to investigate circRNAs expression alteration in serum exosomes derived from OSA patients with AMI. Methods The serum exosomal circRNAs profile of three healthy subjects, three OSA without AMI and three OSA with AMI were analyzed using high-throughput sequencing. Bioinformatic analyses were carried out to assess potential core circRNAs and functional analyses were conducted to study biological functions. Results Compared to healthy subjects, there were 5225 upregulated and 5798 downregulated circRNAs in exosomes from OSA with AMI patients. And our study also identified 5210 upregulated and 5813 downregulated circRNAs in OSA with AMI patients compared to OSA without AMI. The differential expression of 2 circRNAs (hsa_circRNA_101147, hsa_circRNA_101561) between healthy subjects and OSA without AMI, and 4 circRNAs (hsa_circRNA_101328, hsa_circRNA_104172, hsa_circRNA_104640, hsa_circRNA_104642) between healthy subjects and OSA with AMI were confirmed by qRT-PCR. In addition, we demonstrated that miR-29a-3p targeted hsa_circRNA_104642 directly. Conclusions This study demonstrated that there were a number of dysregulated circRNAs in exosomes from OSA with AMI patients, which might be effectively served as a promising diagnostic biomarker and therapeutic targets.

Targeting translation factor proteins holds promise for developing innovative anti-tuberculosis drugs. During protein translation, many factors cause ribosomes to stall at messenger RNA (mRNA). To maintain protein homeostasis, bacteria have evolved various ribosome rescue mechanisms, including the predominant trans-translation process, to release stalled ribosomes and remove aberrant mRNAs. The rescue systems require the participation of translation elongation factor proteins (EFs) and are essential for bacterial physiology and reproduction. However, they disappear during eukaryotic evolution, which makes the essential proteins and translation elongation factors promising antimicrobial drug targets. Here, we review the structural and molecular mechanisms of the translation elongation factors EF-Tu, EF-Ts, and EF-G, which play essential roles in the normal translation and ribosome rescue mechanisms of Mycobacterium tuberculosis (Mtb). We also briefly describe the structure-based, computer-assisted study of anti-tuberculosis drugs.

In recent years, β-glucan has been widely researched in various related fields due to its significant physiological activity and health characteristics. β-glucan exists in highland barley, barley, oats, and microorganisms such as yeast, bacteria fungi and other natural plants, and is a kind of renewable polysaccharide with high nutritional values. Different physical properties due to its extensive sources also affect the development and application of β-glucan in various bioactive functional fields. We have reviewed different sources of β-glucan and its structure-activity relationship, and summarized its research status in digestive system, nervous system, immune system and other aspects, indicating that β-glucan has special physiological activities such as regulating glucose and lipid metabolism disorders, improving immunity and brain function, regulating intestinal microenvironment. It can be used as a dietary supplement and functional factor to intervene and regulate body health, and also has broad application value and prospects in the field of health product research and development. This review will provide theoretical reference and scientific basis for the further development and utilization of β-glucan.

Abstract Background Atrial fibrosis plays a critical role in the development of atrial fibrillation (AF). Exosomes are a promising cell-free therapeutic approach for the treatment of AF. The purposes of this study were to explore the mechanisms by which exosomes derived from atrial myocytes regulate atrial remodeling and to determine whether their manipulation facilitates the therapeutic modulation of potential fibrotic abnormalities during AF. Methods We isolated exosomes from atrial myocytes and patient serum, and microRNA (miRNA) sequencing was used to analyze exosomal miRNAs in exosomes derived from atrial myocytes and patient serum. mRNA sequencing and bioinformatics analyses corroborated the key genes that were direct targets of miR-210-3p. Results The miRNA sequencing analysis identified that miR-210-3p expression was significantly increased in exosomes from tachypacing atrial myocytes and serum from patients with AF. In vitro, the miR-210-3p inhibitor reversed tachypacing-induced proliferation and collagen synthesis in atrial fibroblasts. Accordingly, miR-210-3p knock out (KO) reduced the incidence of AF and ameliorated atrial fibrosis induced by Ang II. The mRNA sequencing analysis and dual-luciferase reporter assay showed that glycerol-3-phosphate dehydrogenase 1-like (GPD1L) is a potential target gene of miR-210-3p. The functional analysis suggested that GPD1L regulated atrial fibrosis via the PI3K/AKT signaling pathway. In addition, silencing GPD1L in atrial fibroblasts induced cell proliferation, and these effects were reversed by a PI3K inhibitor (LY294002). Conclusions Atrial myocyte-derived exosomal miR-210-3p promoted cell proliferation and collagen synthesis by inhibiting GPD1L in atrial fibroblasts. Preventing pathological crosstalk between atrial myocytes and fibroblasts may be a novel target to ameliorate atrial fibrosis in patients with AF. Graphical Abstract

Purpose: Vonoprazan (VPZ) produces a strong acid-inhibitory effect, which can potentially eradicate Helicobacter Pylori (H. pylori). We aimed to assess whether a 14-day VPZ-containing triple therapy was safe and effective in the Chinese population and the potential mechanism.Methods: Enrolled patients confirmed to be infected with H. pylori were randomly divided into four groups: VPZ + doxycycline + furazolidone, VPZ + doxycycline + amoxicillin, esomeprazole (EPZ) + bismuth + doxycycline + furazolidone, and EPZ + colloidal bismuth + doxycycline + amoxicillin for 14 days. The eradication rate, medication adherence, and incidence of adverse events (AEs) were evaluated. Inhibition of H. pylori by VPZ and EPZ in vitro was assessed. H. pylori treated with appropriate concentrations of VPZ and EPZ were sequenced by transcriptome analysis to explore the antibacterial mechanism.Results: A higher eradication rate were observed in VPZ-containing triple therapy. No obvious differences were observed in medication adherence or the incidence of AEs. VPZ had no direct inhibitory effect on H. pylori, whereas EPZ directly inhibited H. pylori may through downregulated genes related to the ribosome.Conclusion: In the Chinese population, 14-day VPZ-containing triple therapy was safe and more effective and can be used clinically as first-line H. pylori treatment.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT05097846

Nickel-based alloys that contain chromium are widely used in corrosion-resistant applications in industry, but they are sensitive to the environment when the passive chromium oxide layer is damaged. In Ni600 and Ni625 alloys, precipitates can deplete the surface layer of chromium oxide. To better characterize and analyze the nickel alloy surfaces and their chromium carbides, chemical etching with different etchants and electrolytic etching were applied to sample surfaces. This paper revealed their efficacy in etching various carbides within the nickel alloys, and orange phases ranging from 2 to 20 μm in optical micrographs were identified as titanium-containing compounds. Carbides located on the grain boundaries were determined to be Cr23C6 and were surrounded by chromium-depleted zones. The findings and figures in this paper provide a more intuitive reference for future analysis of carbides and titanium nitrides, enhancing the understanding of their impact on the corrosion resistance of these alloys, which will not only contribute to the material science field but also aid in developing the Ni-based alloys for industrial applications.

Abstract Background and aims It is crucial to manage the recurrence of Crohn’s disease (CD). This study is aimed to explore whether visceral adipose tissue (VAT) and skeletal muscle (SM) are associated with the recurrence of CD upon different treatments. Methods All patients with a definite diagnosis of CD were retrospectively divided into three groups according to distinct treatment regimens: 5-amino salicylic acid group (Group A), steroids + azathioprine (Group B) and biologics (Group C). The pretreatment computerized tomography (CT) images and clinical data were collected. The VAT area, mesenteric fat index (MFI), the ratio of VAT area to fat mass (VAT area/FM) were assessed. The primary end point was the recurrence of CD within 1 year of follow-up. Results A total of 171 CD patients were enrolled, including 57 (33.33%) patients in Group A, 70 (40.94%) patients in Group B and 44 (25.73%) patients in Group C. Patients with 1-year recurrence had higher MFI (P = 0.011) and VAT area/FM (P = 0.000). ROC curve demonstrated that patients with the ratio of VAT area/FM and MFI higher than 0.578 and 1.394 tended to have recurrence with the AUC of 0.707 and 0.709. Similar results could be observed in Group A & B but not in Group C. Conclusions High VAT area/FM and MFI are related to recurrence within 1 year for newly diagnosed CD patients treated by 5-amino salicylic or azathioprine + steroids rather than biologics. We could not observe any radiological data associated with the recurrence of CD patients under biological treatment.

Synaptic plasticity relies on rapid, yet spatially precise signaling to alter synaptic strength. Arc is a brain enriched protein that is rapidly expressed during learning-related behaviors and is essential for regulating metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). We previously showed that disrupting the ubiquitination capacity of Arc enhances mGluR-LTD; however, the consequences of Arc ubiquitination on other mGluR-mediated signaling events is poorly characterized. Here we find that pharmacological activation of Group I mGluRs with S-3,5-dihydroxyphenylglycine (DHPG) increases Ca2+ release from the endoplasmic reticulum (ER). Disrupting Arc ubiquitination on key amino acid residues enhances DHPG-induced ER-mediated Ca2+ release. These alterations were observed in all neuronal subregions except secondary branchpoints. Deficits in Arc ubiquitination altered Arc self-assembly and enhanced its interaction with calcium/calmodulin-dependent protein kinase IIb (CaMKIIb) and constitutively active forms of CaMKII in HEK293 cells. Colocalization of Arc and CaMKII was altered in cultured hippocampal neurons, with the notable exception of secondary branchpoints. Finally, disruptions in Arc ubiquitination were found to increase Arc interaction with the integral ER protein Calnexin. These results suggest a previously unknown role for Arc ubiquitination in the fine tuning of ER-mediated Ca2+ signaling that may support mGluR-LTD, which in turn, may regulate CaMKII and its interactions with Arc.

Abstract Background The azygos lobe (AL) combined with partial anomalous pulmonary venous return (PAPVR) is comparatively uncommon as well as in radical surgery for right lung cancer. Case presentation We herein present an extremely rare case of lung cancer coexisting with AL and asymptomatic PAPVR, which was diagnosed with preoperative contrast three-dimensional reconstruction and received radical surgery by thoracoscopy. During the surgery, we preserved azygos vein successfully and found a split type of PAPVR in right upper pulmonary vein. Conclusions AL combined with PAPVR may cause confusion on the vascular separation and disconnection of the right pulmonary hilar. However, preoperative 3D reconstruction is more conducive to the correct performing of this type of surgery.

Forest ecological function is one of the key indicators reflecting the quality of forest resources. The traditional weighting method to assess forest ecological function is based on a large amount of ground survey data; it is accurate but costly and time-consuming. This study utilized three machine learning algorithms to estimate forest ecological function levels based on multi-source data, including Sentinel-2 optical remote sensing images and digital elevation model (DEM) and forest resource planning and design survey data. The experimental results showed that Random Forest (RF) was the optimal model, with overall accuracy of 0.82, recall of 0.66, and F1 of 0.62, followed by CatBoost (overall accuracy = 0.82, recall = 0.62, F1 = 0.58) and LightGBM (overall accuracy = 0.76, recall = 0.61, F1 = 0.58). Except for the indicators from remote sensing images and DEM data, the five ground survey indicators of forest origin (QI_YUAN), tree age group (LING_ZU), forest category (LIN_ZHONG), dominant species (YOU_SHI_SZ), and tree age (NL) were used in the modeling and prediction. Compared to the traditional methods, the proposed algorithm has lower cost and stronger timeliness.

Poorly differentiated hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis. Here the authors show that GDF1, a member of the TGF-β superfamily, is highly expressed in high-grade poorly differentiated HCC and is associated with tumor plasticity, and that GDF1-induced reexpression of cancer testis antigens could render tumors sensitive to immune checkpoint inhibition.

Abstract Human gastrointestinal malignancies are highly heterogeneous cancers. Clinically, heterogeneity largely contributes to tumor progression and resistance to therapy. Heterogeneity within gastrointestinal cancers is defined by molecular subtypes in genomic and transcriptomic analyses. Cancer stem cells (CSCs) have been demonstrated to be a major source of tumor heterogeneity; therefore, assessing tumor heterogeneity by CSC trait-guided classification of gastrointestinal cancers is essential for the development of effective therapies. CSCs share critical features with embryonic stem cells (ESCs). Molecular investigations have revealed that embryonic genes and developmental signaling pathways regulating the properties of ESCs or cell lineage differentiation are abnormally active and might be oncofetal drivers in certain tumor subtypes. Currently, multiple strategies allow comprehensive identification of tumor subtype-specific oncofetal signatures and evaluation of subtype-specific therapies. In this review, we summarize current knowledge concerning the molecular classification of gastrointestinal malignancies based on CSC features and elucidate their clinical relevance. We also outline strategies for molecular subtype identification and subtype-based therapies. Finally, we explore how clinical implementation of tumor classification by CSC subtype might facilitate the development of more effective personalized therapies for gastrointestinal cancers.

Abstract Mode matching is a widely used method in various electromagnetic problems due to its dimensional advantages. However, the numerical implementation of mode matching is challenged by its high computational complexity in solving eigenvalue problems. The Lanczos method approximates the original eigenvalue problem in an efficient way and transforms the mode matching into an implicit form. The price of efficiency enhancement is the loss of eigenmode accuracy and behaviour interpretation. Its numerical efficiency is also influenced by block matrix dimensions while solving multi‐junctional waveguide structures. This work proposes a novel structure eigenmode restoration algorithm based on the Krylov subspace method. The method takes the conventional explicit mode matching strategy, but the efficiency enhancement for solving eigenmodes is prominent. The overall computational complexity is reduced from the original O(N3) to O(N1.5) without the cost of eigenmode accuracy loss. Numerical benchmark cases verify the proposed method’s accuracy and efficiency. The efficiency advantage is outstanding especially in computational time. Extra discussions about eigenmode selection strategies based on accuracy controlling indicate that the proposed method possesses better flexibility in solving complicated waveguide problems.

Summary: Here, we present a detailed protocol for the identification of potential oncofetal targets for hepatocellular carcinoma (HCC) patients through a hepatocyte differentiation model and a sorafenib refractory cell-line-derived xenograft model. We describe the procedures of tumor sphere formation, organoid generation, and subcutaneous tumor formation for functional studies. We then detail the procedures of immunohistochemistry and immunofluorescence for examination of changes in lineage-specific markers. Finally, we describe the development of antibody-based therapeutics targeting tumor lineage plasticity in HCC.For complete details on the use and execution of this protocol, please refer to Kong et al. (2021).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Autophagy is an important biological process in normal cells. However, how it affects tumor progression still remains poorly understood. Herein, we demonstrated that the oncogenic protein Chromodomain-helicase-DNA-binding-protein 1-like gene (CHD1L) might promote HCC cells migration and metastasis through autophagy. CHD1L could bind to the promotor region of Zinc finger with KRAB and SCAN domain 3 (ZKSCAN3), a pivotal autophagy suppressor, and inhibit its transcription. We established inducible CHD1L conditional knockout cell line (CHD1L-iKO cell) and found that the deletion of CHD1L significantly increased ZKSCAN3 expression both at mRNA and protein level. Deletion of CHD1L impaired the autophagic flux and migration of HCC cells, while specifically inhibiting ZKSCAN3 blocked these effects. Further exploration demonstrated that the enhanced tumor cell migration and metastasis induced by CHD1L was mediated through ZKSCAN3-induced autophagic degradation of Paxillin. In summary, we have characterized a previously unknown function of CHD1L in regulating tumor migration via ZKSCAN3-mediated autophagy in HCC. Further inhibition of CHD1L and its downstream autophagy signaling might shed new light on cancer therapeutics.