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Abstract Background Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC. Methods This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1–14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14–15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. Discussion In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer. Trial registration This study was registered at www.clinicaltrials.gov . Trial registration number: NCT05972655. Date of registration: 31 July 2023.

Abstract Recent studies have implicated the phenazine biosynthesis-like domain-containing protein (PBLD) in the negative regulation of the development and progression of various cancers. However, its function in viral infection remains unknown. In this study, we found that PBLD plays important roles in multiple virus infections including BPIV3, SeV, VSV, and HSV-1. Our study revealed that PBLD enhances the expression of type I interferon (IFN-I) and ISGs through interferon regulatory factor 3 (IRF3). Further study indicated that PBLD promotes transcriptional phosphorylation of IRF3 (S385/386), thereby facilitating virus-induced IFN-I production. Interestingly, PBLD mediates virus-triggered mitochondrial apoptosis through its dependence on IRF3 (K313/315). Mechanistically, PBLD facilitated virus-induced apoptosis by recruiting the Puma protein to the mitochondria via IRF3. Additionally, we performed mutational analyses of IRF3, showing that its loss of either transcriptional or apoptotic function markedly increased viral replication. Moreover, macrophages with PBLD deficiency during viral infection exhibited decreased the IFN-I and ISGs expression, exacerbating viral infection. Importantly, mice deficient in PBLD exhibited increased viral replication and susceptibility to SeV infection, leading to decreased survival. Notably, Cedrelone, a chemical activator of PBLD, has the ability to reduce SeV replication. Collectively, we first discovered the new function of PBLD in viral infection, broadening our understanding of potential therapeutic targets and offering new insights for antiviral drug development.

Abstract In engineered photonic lattices, topological photonic (TP) modes present a promising avenue for designing waveguides with suppressed backscattering. However, the integration of the TP modes in electromagnetic systems has faced longstanding challenges. The primary obstacle is the insufficient development of high‐efficiency coupling technologies between the TP modes and the conventional transmission modes. This dilemma leads to significant scattering at waveguide terminals when attempting to connect the TP waveguides with other waveguides. In this study, a topological photonic substrate‐integrated waveguide (TPSIW) is proposed that can seamlessly integrate into traditional microstrip line systems. It successfully addresses the matching problem and demonstrates efficient coupling of both even and odd TP modes with the quasi‐transverse electromagnetic modes of microstrip lines, resulting in minimal energy losses. In addition, topological leaky states are introduced through designed slots on the TPSIW top surface. These slots enable the creation of TP leaky‐wave antennas with beam steering capabilities. A wireless link based on TPSIWs are further established that enables the transmission of distinct signals toward different directions. This work is an important step toward the integration of TP modes in microwave systems, unlocking the possibilities for the development of high‐performance wireless devices.

The aim of this study was to identify Artemis as a predictive biomarker for guiding preoperative chemoradiotherapy in locally advanced rectal cancer. The resection specimens were collected from 50 patients with rectal cancer who underwent preoperative chemoradiotherapy. Artemis expression in biopsy tissues was evaluated using immunohistochemical staining according to the percentage of positively stained cells combined with staining intensity. Among the 50 patients, 36 (72%) had a weakly positive Artemis protein expression, 10 (20%) had a moderately positive expression, and 4 (8%) showed a strongly positive expression. The criteria of magnetic resonance imaging tumor regression grade (mrTRG) and pathological rectal cancer regression grade (RCRG) were used to assess the tumor response to chemoradiotherapy. Correlation analysis shows that there is a significant negative correlation between high Artemis immunoscore and treatment response (r = −0.532, p < 0.001). The results imply that high Artemis expression was associated with poor treatment response. Our study suggested a potential role of Artemis as a predictive biomarker of the tumor response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

Laccase (LAC), a copper-containing polyphenol oxidase, is an important pathogenic factor of pathogenic fungi, and has been identified as an important virulence factor in numerous pathogenic fungi. LAC is encoded by a gene family and belongs to the class of multicopper oxidases. The study aimed to identify the LAC genes in Athelia bombacina (Link) Pers, and their interactions with the host. The expression levels of the LAC genes were quantified using RT-qPCR. The LAC activity, level of malondialdehyde (MDA) and activities of protective enzymes in ‘Huangguan’ pears during the interaction were measured. The AbLac4 gene deletion mutant strain was constructed. Six LAC genes were identified in A. bombacina, distributed across three chromosomes. Interspecies collinearity analysis suggested that LAC genes could serve as crucial pathogenic factors in A. bombacina. The LAC gene family can be classified into three distinct subgroups. Among the subgroups, variations were observed in their characteristic sequences and conserved motifs. However, the LAC genes within the same subgroup exhibited a high degree of conservation. The genes showed diverse expression profiles, with their promoters harboring multiple stress-responsive elements. Signal peptide prediction showed that all LAC proteins, with the exception of the AbLac3 protein, possessed signal peptides, indicating that they are secretory proteins. The subcellular localization analysis showed that all LAC proteins may be localized extracellularly. RT-qPCR revealed differential expression patterns among LAC genes; specifically, AbLac1 and AbLac4 exhibited distinct expression dynamics during the infection process. The LAC activity first increased and then decreased, with the highest increase rate occurring in the early stage of culture. The MDA content and catalase (CAT) activity at the inoculated site were found to be significantly higher than the uninoculated control. In addition, the deletion of AbLac4 gene reduced the growth rate and pathogenic ability of A. bombacina. This investigation found that AbLac1 and AbLac4 may play pivotal roles in mediating host interactions, and the fruit may combat pathogen infection through increasing the activities of CAT, phenylalanine ammonia lyase and peroxidase. This study provides valuable new insights into the pathogenic mechanisms of A. bombacina, significantly contributing to the field.

Radiotherapy stands as a cornerstone in the treatment of numerous malignant tumors, including non-small cell lung cancer. However, the critical challenge of amplifying the tumoricidal effectiveness of radiotherapy while minimizing collateral damage to healthy tissues remains an area of significant research interest. Radiosensitizers, by methods such as amplifying DNA damage and fostering the creation of free radicals, play a pivotal role in enhancing the destructive impact of radiotherapy on tumors. Over recent decades, nano-dimensional radiosensitizers have emerged as a notable advancement. Their mechanisms include cell cycle arrest in the G2/M phase, combating tumor hypoxia, and others, thereby enhancing the efficacy of radiotherapy. This review delves into the evolving landscape of nanomaterials used for radiosensitization in non-small cell lung cancer. It provides insights into the current research progress and critically examines the challenges and future prospects within this burgeoning field.

Valosin-containing protein (VCP), an ATPase-associated protein, is emerging as a crucial regulator in cardiac pathologies. However, the pivotal role of VCP in the heart under physiological conditions remains undetermined. In this study, we tested a hypothesis that sufficient VCP expression is required for cardiac development and physiological cardiac function. Thus, we generated a cardiac-specific VCP knockout (KO) mouse model and assessed the consequences of VCP suppression on the heart through physiological and molecular studies at baseline. Our results reveal that homozygous KO mice are embryonically lethal, whereas heterozygous KO mice with a reduction in VCP by ~40% in the heart are viable at birth but progressively develop heart failure and succumb to mortality at the age of 10 to 12 months. The suppression of VCP induced a selective activation of the mammalian target of rapamycin complex 1 (mTORC1) but not mTORC2 at the early age of 12 weeks. The prolonged suppression of VCP increased the expression (by ~2 folds) and nuclear translocation (by >4 folds) of protein phosphatase 1 (PP1), a key mediator of protein dephosphorylation, accompanied by a remarked reduction (~80%) in AKTSer473 phosphorylation in VCP KO mouse hearts at a later age but not the early stage. These temporal molecular alterations were highly associated with the progressive decline in cardiac function. Overall, our findings shed light on the essential role of VCP in the heart under physiological conditions, providing new insights into molecular mechanisms in the development of heart failure.

BackgroundInjuries are a leading cause of death in the United States. Trauma systems aim to ensure all injured patients receive appropriate care. Hospitals that participate in a trauma system, trauma centers (TCs), are designated with different levels according to guidelines that dictate access to medical and research resources but not specific surgical care. This study aimed to identify patterns of injury care that distinguish different TCs and hospitals without trauma designation, non-trauma centers (non-TCs).Study designWe extracted hospital-level features from the state inpatient hospital discharge data in Washington state, including all TCs and non-TCs, in 2016. We provided summary statistics and tested the differences of each feature across the TC/non-TC levels. We then conducted 3 sets of unsupervised clustering analyses using the Partition Around Medoids method to determine which hospitals had similar features. Set 1 and 2 included hospital surgical care (volume or distribution) features and other features (e.g., the average age of patients, payer mix, etc.). Set 3 explored surgical care without additional features.ResultsThe clusters only partially aligned with the TC designations. Set 1 found the volume and variation of surgical care distinguished the hospitals, while in Set 2 orthopedic procedures and other features such as age, social vulnerability indices, and payer types drove the clusters. Set 3 results showed that procedure volume rather than the relative proportions of procedures aligned more, though not completely, with TC designation.ConclusionUnsupervised machine learning identified surgical care delivery patterns that explained variation beyond level designation. This research provides insights into how systems leaders could optimize the level allocation for TCs/non-TCs in a mature trauma system by better understanding the distribution of care in the system.

Abstract Background Health literacy is closely related to health status. Measuring public health literacy levels helps to warn of health status and manage health problems through timely interventions. The items of relevant evaluation tools are complex and numerous in China, and there is no recognized health literacy brief scale for the whole population. To translate the 12-item short-form health literacy scale (HLS-SF12) and test the validity and reliability of the Chinese version of the HLS-SF12 in the Chinese population. Methods The HLS-SF12 was translated into Chinese using the procedures of translation, back translation, and cultural debugging. 10,951 residents were selected by quota sampling method to test the validity and reliability of the scale, and 33 people were selected to retest after 2 weeks. The reliability was tested by using internal consistency coefficient and test-retest reliability. The validity was tested by using confirmatory factor analysis, content validity, convergent validity and discriminant validity. Results The Cronbach’s Alpha coefficient for the total scale was 0.94, and the test-retest reliability was 0.89. The Cronbach’s Alpha coefficients for the three subscales of health care, disease prevention, and health promotion respectively were 0.86, 0.86, 0.87, and the test-retest reliability respectively were 0.91, 0.79, 0.63. The confirmatory factor analysis identified a three factors model and showed nice goodness of fit indices for Chinese HLS-SF12 (GFI = 0.96, CFI = 0.97, IFI = 0.97, TLI = 0.96, and RMSEA = 0.07). Conclusion The Chinese version of the HLS-SF12 has good reliability and validity, and can be used as a tool to evaluate the health literacy of Chinese people.

IntroductionThe efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear.Methods3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer’s tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment.ResultsBased on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs.DiscussionThe use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

BackgroundThe obesity rate in the Chinese population is increasing and there is a lack of short and reliable scales for measuring obesity-related eating behavior in China. The EBS-SF (Sakata Eating Behavior Scale short form) has only 7 entries and has shown good reliability in studies such as those in Japan.ObjectiveTo translate the EBS-SF into Chinese, check its reliability, validity and explore the related factors.MethodThe EBS-SF was translated into Chinese. 3,440 residents were investigated and 34 respondents were retested. Item analysis and reliability and validity tests were carried out. Personality characteristics, family health status and depression were investigated using the BFI-10, FHS-SF and PHQ-9 to investigate the factors associated with EBS-SF. The t-test, ANOVA and Pearson correlation was used to explore the related factors of its scores.ResultAmong 3,440 residents, 1,748 (50.81%) were male and 1,692 (49.19%) were female; 1,373 (39.91%) were aged 36–50 years. All 7 items were qualified in the item analysis. As for reliability, the Cronbach's α was 0.870, the split-half reliability was 0.830, the test-retest correlation coefficient was 0.868. As for the structural validity, the standardized factor loadings were above 0.50, χ2 / df = 2.081,GFI = 0.999; NFI = 0.999; RFI = 0.996; RMSEA = 0.018, all qualified. The characteristics, personality, family health and depression were correlated with the score of the Chinese version of EBS short form.ConclusionThe structural validity and reliability of the Chinese version of the EBS-SF are good and it can be used as a measurement tool to evaluate the eating behavior of Chinese. The scores of the EBS-SF may be related to the sociological characteristics, personality, family health, and depression status.

Barbituric acid derivative (TDPT) is an achiral molecule, and its adsorption on a surface results in two opposite enantiomerically oriented motifs, namely TDPT-Sp and Rp. Two types of building blocks can be formed; block I is enantiomer-pure and is built up of the same motifs (format SpSp or RpRp) whereas block II is enantiomer-mixed and composes both motifs (format SpRp), respectively. The organization of the building blocks determines the formation of different nanoarchitectures which are investigated using scanning tunneling microscopy at a liquid/HOPG interface. Sophisticated, highly symmetric “nanowaves” are first formed from both building blocks I and II and are heterochiral. The “nanowaves” are metastable and evolve stepwisely into more close-packed “nanowires” which are formed from enantiomer-pure building block I and are homochiral. A dynamic hetero- to homochiral transformation and simultaneous multi-scale phase transitions are demonstrated at the single-molecule level. Our work provides novel insights into the control and the origin of chiral assemblies and chiral transitions, revealing the various roles of enantiomeric selection and chiral competition, driving forces, stability and molecular coverage.

In recent years, with the rapid development of integrated circuits, the filtering antenna (FA) circuit of the substrate integrated waveguide (SIW) has attracted widespread attention in wireless communications. Numerous structures have been proposed to improve the performance of SIW FA. Hence, this paper presents the development and miniaturization trend of the SIW FA, and briefly introduces the structure and historical development of the SIW FA. In terms of the mode, multi-mode cavities and incomplete mode cavities are constructed. Multi-layer structures, special structures and the slow-wave technology are constructed in physical structure. Several methods and design examples of the SIW FA miniaturization are introduced from these two aspects. Based on the combination of the filter and antenna, the FA remains the advantages of the SIW structure, mainly including small size, low insertion loss, high quality-factors, and easy integration in planar radio frequency components. Therefore, it can further reduce the circuit, allowing SIW FAs to be applied in many aspects such as the 5G (5th generation mobile communication technology) and wireless local area network communications.

Current treatments for advanced hepatocellular carcinoma (HCC) have limited success in improving patients’ quality of life and prolonging life expectancy. The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies. Recently, there has been increased interest in oncolytic viruses (OVs) as a therapeutic modality for HCC. OVs undergo selective replication in cancerous tissues and kill tumor cells. Strikingly, pexastimogene devacirepvec (Pexa-Vec) was granted an orphan drug status in HCC by the U.S. Food and Drug Administration (FDA) in 2013. Meanwhile, dozens of OVs are being tested in HCC-directed clinical and preclinical trials. In this review, the pathogenesis and current therapies of HCC are outlined. Next, we summarize multiple OVs as single therapeutic agents for the treatment of HCC, which have demonstrated certain efficacy and low toxicity. Emerging carrier cell-, bioengineered cell mimetic- or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described. In addition, we highlight the combination treatments between oncolytic virotherapy and other modalities. Finally, the clinical challenges and prospects of OV-based biotherapy are discussed, with the aim of continuing to develop a fascinating approach in HCC patients.

This research focuses on one of the three components of the fraud triangle, namely opportunity, and empirically tests the tendency to commit fraud. The perceived opportunity to commit fraud can be considered in terms of temptation and obstacles. This research employs concepts from cognitive psychology, i.e., desire and motivation for action, which affect people’s decision-making processes when presented with an opportunity to commit fraud. Questionnaires were used to analyze the tendency to commit fraud. First, dispositional differences among people differing in self-control were observed, which may influence the likelihood of fraudulent behavior. That is, low self-control mediates the relationship between self-regard and fraud tendency. Second, strong relationships of both personal disposition and self-efficacy with the tendency to commit fraud were revealed; high self-efficacy enhances the tendency to commit fraud. This research offers a new psychological perspective on fraud opportunity, and showing for the first time that fraud can be reduced not only by improved internal control and external supervision, as suggested in previous studies, but also by changing people’s perceptions of fraud opportunity, given the fallibility of both internal control and external supervision.

Globisporangium, especially G. sylvaticum, causes devastating root rot, blight, and other diseases in various species of cash crops. To investigate the distribution and host range of G. sylvaticum in Guizhou, a suitable habitat for this pathogen, we collected 156 root-diseased samples, isolated the pathogens, and found that G. sylvaticum is widespread and has eleven host plants, including four novel hosts. Furthermore, to effectively identify G. sylvaticum, we developed a simple and dependable method based on loop-mediated isothermal amplification (LAMP), which used a primer set designed from the internal transcribed spacer sequences with high specificity and sensitivity of 1 pg/μL. Additionally, to perform field identification, we used the “Plant-LAMP” method with crude DNA extraction to detect the pathogen in 45 root samples from nine species of plants. Our results showed that this method could effectively detect G. sylvaticum in diseased roots. Therefore, our findings not only enrich existing research on the diversity of pathogenic Globisporangium in Guizhou but also present an efficient LAMP field detection method that could significantly contribute to plant disease management and prevention.

As a devastating wheat disease, Fusarium head blight (FHB) causes large losses in yield and quality. The purpose of this study was to detect the genetic loci for FHB resistance based on a genome-wide association study (GWAS) using two panels genotyped by the Wheat 660 K SNP array and Wheat 90 K SNP array. Phenotypic investigation results showed that 43.6–51.6% of the test varieties showed an infection type of more than 3, indicating that substantial improvement in the level of resistance was urgently required. GWAS detected 1264 SNPs associated with FHB response distributed on all wheat chromosomes. Fourteen QTL were stably detected in two environments. gFHB-1B (582.9~607.9 Mb on chromosome 1B) and gFHB-5A (577.9~596.5 Mb on 5A) were two novel resistance loci that were detected in two wheat panels. Haplotype analysis of both gFHB-1B and gFHB-5A indicated that varieties with gFHB-1B_R and gFHB-5A_R had consistently less FHB than varieties carrying a one or no resistance QTL. The application frequency of the FHB-resistant alleles gFHB-1B and gFHB-5A showed a gradually decreasing trend in FHB resistance breeding. This study identified new genetic loci for the control of FHB and provides useful information for marker-assisted selection in wheat FHB resistance.

(1) Background: An increasing amount of research has supported the role of radiomics for predicting pathological complete response (pCR) to neoadjuvant chemoradiation treatment (nCRT) in order to provide better management of locally advanced rectal cancer (LARC) patients. However, the lack of validation from prospective trials has hindered the clinical adoption of such studies. The purpose of this study is to validate a radiomics model for pCR assessment in a prospective trial to provide informative insight into radiomics validation. (2) Methods: This study involved a retrospective cohort of 147 consecutive patients for the development/validation of a radiomics model, and a prospective cohort of 77 patients from two institutions to test its generalization. The model was constructed using T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI to understand the associations with pCR. The consistency of physicians’ evaluations and agreement on pathological complete response prediction were also evaluated, with and without the aid of the radiomics model. (3) Results: The radiomics model outperformed both physicians’ visual assessments in the prospective test cohort, with an area under the curve (AUC) of 0.84 (95% confidence interval of 0.70–0.94). With the aid of the radiomics model, a junior physician could achieve comparable performance as a senior oncologist. (4) Conclusion: We have built and validated a radiomics model with pretreatment MRI for pCR prediction of LARC patients undergoing nCRT.

BackgroundLocally advanced rectal cancers (LARC) show a highly variable response to neoadjuvant chemoradiotherapy (nCRT), and the impact of the tumor immune response in this process is poorly understood. This study aimed to characterize the immune-related gene expression profiles (GEP), pathways, and cell types associated with response or resistance to neoadjuvant chemoradiotherapy.MethodsThe transcriptomic and clinical data of Rectal carcinoma from the Gene Expression Omnibus database and Immune-related genes (IRGs) from ImmPort were downloaded to identify the differentially expressed immune-related genes (DEIRGs) between responder and non-responder to neoadjuvant chemoradiotherapy. Gene set enrichment analyses were performed to uncover significantly enriched GO terms and KEGG pathways. Immune cell infiltration was estimated from RNA-sequencing data using ImmuCellAI. Afterward, we constructed an immune-related gene-based predictive model (IRGPM) by Support Vector Machine and validated it in an external cohort.ResultA 15-gene signature (HLA-DPB1, HLA-DQA1, CXCL9, CXCL10, TAP2, INHBB, BMP2, CD74, IL33, CCL11, CXCL11, DEFB1, HLA-DPA1, CCN3, STAT1) was identified as DEIRGs and found to be significantly associated with nCRT outcomes. Gene set enrichment analyses indicated that the 15 genes play active roles in inflammation-related biological processes. In addition, ImmuCellAI revealed that CD4 naive T cells, Tex, Th1 were significantly up-regulated (p=0.035, p=0.02, p=0.0086, respectively), while Tfh were significantly down-regulated (p=0.015) in responder subgroup. Finally, a novel predictive model was developed by SVM based on DEIRGs with an AUC of 80% (internal validation) and 73.5% (external validation).ConclusionOur team conducted a genomic study of the relationship between gene expression profile and response to nCRT in LARC. Our data suggested that the DEIRGs signature could help predict the efficacy of nCRT. And a DEIRGs‐based SVM model was developed to monitor the outcomes of nCRT in LARC.

Teachers and parents are key participants in the growth of secondary vocational students, and can jointly support them. This study aimed to explore how the support of teachers and parents affects the academic performance of secondary vocational students and to reveal the ‘black box’ mechanism for their interaction and relationship. We adapted a Chinese version of a scale for secondary vocational students’ perception of teacher and parent support, drawing on self-determination theory. A survey was conducted through the Chinese questionnaire platform wjx.cn, and respondents were fully informed about the research. Data were collected from 710 secondary vocational students in Shanghai and analyzed using SPSS and AMOS. Our hypothesis model was verified, with results indicating that the support of autonomy, emotion, and ability provided by parents and teachers has a significant impact on students’ academic performance. The degree of learning engagement plays a mediating role in the relationship between support and achievement. The achievement goal orientation of students can adjust individual learning engagement, and further, affect the influence of teacher and parent support on academic performance. Teacher and parent support interactively influence learning engagement. The study findings suggest that an optimization strategy is needed to promote the academic improvement of secondary vocational students to meet students’ basic psychological needs and promote cooperation between family and school. Parents and teachers should also consider the impact of learning engagement and the learning process, and offer guidance in developing an appropriate achievement goal orientation and a positive learning concept.

Curriculum sequencing problem is crucial to e-learning system, which is a NP-hard optimization problem and commonly solved by swarm intelligence. As a form of swarm intelligence, particle swarm optimization (PSO) is widely used in various kinds of optimization problems. However, PSO is found ineffective in complex optimization problems. The main reason is that PSO is ineffective in diversity preservation, leading to high risks to be trapped by the local optima. To solve this problem, a novel hybrid PSO algorithm is proposed in this study. First, a competitive-genetic crossover strategy is proposed for PSO to balance the convergence and diversity. Second, an adaptive polynomial mutation is introduced in PSO to further improve its diversity preservation ability. Furthermore, a curriculum scheduling model is proposed, where several constraints are taken into considerations to ensure the practicability of the curriculum sequencing. The numerical comparison experiments show that the proposed algorithm is effective in solving function optimization in comparison to several popular PSO variants; furthermore, for the optimization of the designed curriculum sequencing problem, the proposed algorithm shows significant advantages over the compared algorithms with respect to the degree of the satisfaction of the objectives, i.e., 20, 14, and 5 percentages higher, respectively.

Diarylethene is a prototypical molecular switch that can be reversibly photoisomerized between its open and closed forms. Ligands bpy-DAE-bpy, consisting of a phenyl-diarylethene-phenyl (DAE) central core and bipyridine (bpy) terminal substituents, are able to self-organize. They are investigated by scanning tunneling microscopy at the solid–liquid interface. Upon light irradiation, cooperative photochromic switching of the ligands is recognized down to the submolecular level. The closed isomers show different electron density of states (DOS) contrasts, attributed to the HOMO or LUMO molecular orbitals observed. More importantly, the LUMO images show remarkable differences between the open and closed isomers, attributed to combined topographic and electronic contrasts mainly on the DAE moieties. The electronic contrasts from multiple HOMO or LUMO distributions, combined with topographic distortion of the open or closed DAE, are interpreted by density functional theory (DFT) calculations.

Polymers obtained by on-surface chemistry have emerged as a class of promising materials. Here, we propose a new strategy to obtain self-assembled 1D polymers by using photochemical [2+2] cyclo-addition or by using a mild thermal annealing. All nanostructures are fully characterized by using scanning tunneling microscopy at ambient conditions on a graphite surface. We demonstrated that nature of the stimulus strongly alters the overall quality of the resulting polymers in terms of length and number of defects. This new way is an efficient method to elaborate on-surface self-assembled 1D polymers.

To provide the general information on corneal transplantation (CT) in China, China Cornea Society designed a questionnaire on CT from 2014 to 2018 and entrusted it to 31 committee members for implementation of the survey nationwide. This article presents the results of the survey and compares the indicators used in the survey and those in the annual statistical report released by the Eye Bank Association of America (EBAA). The number of corneal transplantations completed by the 64 hospitals from 2014 to 2018 was respectively 5377, 6394, 7595, 8270 and 8980, totally 36,616 (22,959 male and 13,657 female). The five largest hospitals by the number of corneal transplantations completed 15,994 surgeries in total, accounting for 43.68% of all the surgeries performed in the 64 hospitals. The most common indication for corneal transplantations was corneal leukoma (7683, 20.98%), followed by bacterial keratitis (4209, 11.49%), corneal dystrophies (4189, 11.44%), keratoconus (3578, 9.77%) and corneal perforation (2839, 7.75%). The main surgical techniques were penetrating keratoplasty (PK) (19,896, 54.34%), anterior lamellar keratoplasty (ALK) (13,869, 37.88%). The proportion of PK decreased from 57.97% in 2014 to 52.88% in 2018 while the proportion of ALK increased from 36.04% in 2014 to 37.92% in 2018. The geographical distribution of keratoplasties performed in China is unbalanced. PK and ALK were the main techniques of CT and corneal leukoma, bacterial keratitis and corneal dystrophies were the main indications for CT in China.

Background/Aims: Bile duct cancer, although not among the most common tumors, still accounts for more and more worldwide deaths each year. By attempting to verify an overexpression of ALDOA in cholangiocarcinoma tissues and cells and explore the underlying molecular mechanism regulated by miR-122-5p, this study was designed to provide a potential molecular target in bile duct cancer treatment. Methods: Western blot and immunohistochemistry were performed to detect the ALDOA protein level in duct carcinoma tissues. The transfection efficiency was confirmed by western blot and/or RT-qPCR assay. The proliferation of bile duct carcinoma cells was determined by MTT and colony formation assay. The invasion ability of bile duct carcinoma cells was evaluated with Transwell invasion assay. Flow cytometry detected cell apoptosis of bile duct carcinoma cells. The miRNAs which modulate ALDOA were filtrated from bioinformatics software and clinical specimens. The target relationship was confirmed by dual luciferase reporter assay. Furthermore, a xenograft model was completed to verify the impact of miRNA on inhibition growth of bile duct carcinoma cells. Results: ALDOA was found up-regulated in bile duct carcinoma tissues and cells. Knockdown of ALDOA promoted the apoptosis of cells and inhibited the proliferation and invasion of bile duct carcinoma cells. Bioinformatics and clinical specimens indicated the negative correlation and targeted regulation between miR-122-5p and ALDOA. By down-regulating ALDOA, overexpression of miR-122-5p appeared to promote cell apoptosis and significantly inhibit cell proliferation, invasion in vitro and suppress the tumor growth in vivo. Conclusion: miR-122-5p inhibited proliferation and invasion of bile duct carcinoma cells and promoted cell apoptosis by targeting ALDOA expression.

Abstract With high sensitivity at single molecule level, surface-enhanced Raman scattering (SERS) is considered as an ultrasensitive optical detection technology with broad application prospects in lots of fields. However, the complicated fabrication and unaffordable price of SERS substrate are still a roadblock on the way to be widely used in industry. In this work, the SERS spectra on a commercial laser engraved Teflon (PTFE) film with engraved microarray are investigated. The wettability of film surface modulated by laser engraving make the microarray have the ability to decrease the contact area on film surface while water evaporation. The SEM image of the engraved area points out the micro/nanostructures generated engraving process is crucial to its superhydrophobic property. The probing molecules (i.e., methylene blue and rhodamine6G) were utilized to investigate with the limit of detection (1 × 10−14 M). Furthermore, the biomolecule (bovine serum albumin) was used to demonstrate its benefits in biological applications. The measured intensities of Raman spectra on this PTFE with laser engraved microarray demonstrate its potential value for a SERS substrate. Our work on this simple, cheap SERS substrate with high sensitivity has a great commercial value and plenty of application in lots of fields.

Abstract Benefiting from the induced image charge on metal film, the light energy is confined on a film surface under metal nanoparticle dimer, which is called electromagnetic field redistribution. In this work, electromagnetic field distribution of metal nanoparticle monomer or dimer on graphene is investigated through finite-difference time-domain method. The results point out that the electromagnetic field (EM) redistribution occurs in this nanoparticle/graphene hybrid system at infrared region where light energy could also be confined on a monolayer graphene surface. Surface charge distribution was analyzed using finite element analysis, and surface-enhanced Raman spectrum (SERS) was utilized to verify this phenomenon. Furthermore, the data about dielectric nanoparticle on monolayer graphene demonstrate this EM redistribution is attributed to strong coupling between light-excited surface charge on monolayer graphene and graphene plasmon-induced image charge on dielectric nanoparticle surface. Our work extends the knowledge of monolayer graphene plasmon, which has a wide range of applications in monolayer graphene-related film.

Small heat shock protein 22 (HSP22) belongs to the superfamily of heat shock proteins and is predominantly expressed in the heart, brain, skeletal muscle, and different types of cancers. It has been found that HSP22 is involved in variant cellular functions in cardiomyocytes and plays a vital role in cardiac protection against cardiomyocyte injury under diverse stress. This review summarizes the multiple functions of HSP22 in the heart and the underlying molecular mechanisms through modulating gene transcription, post-translational modification, subcellular translocation of its interacting proteins, and protein degradation, facilitating mitochondrial function, cardiac metabolism, autophagy, and ROS production and antiapoptotic effect. We also discuss the association of HSP22 in cardiac pathologies, including human dilated cardiomyopathy, pressure overload-induced heart failure, ischemic heart diseases, and aging-related cardiac metabolism disorder. The collected information would provide insights into the understanding of the HSP22 in heart diseases and lead to discovering the therapeutic targets.

Valosin-containing protein (VCP) was found to play a vital protective role against cardiac stresses. Genetic mutations of VCP are associated with human dilated cardiomyopathy. However, the essential role of VCP in the heart during the physiological condition remains unknown since the VCP knockout in mice is embryonically lethal. We generated a cardiac-specific dominant-negative VCP transgenic (DN-VCP TG) mouse to determine the effects of impaired VCP activity on the heart. Using echocardiography, we showed that cardiac-specific overexpression of DN-VCP induced a remarkable cardiac dilation and progressively declined cardiac function during the aging transition. Mechanistically, DN-VCP did not affect the endogenous VCP (EN-VCP) expression but significantly reduced cardiac ATPase activity in the DN-VCP TG mouse hearts, indicating a functional inhibition. DN-VCP significantly impaired the aging-related cytoplasmic/nuclear shuffling of EN-VCP and its co-factors in the heart tissues and interrupted the balance of the VCP-cofactors interaction between the activating co-factors, ubiquitin fusion degradation protein 1 (UFD-1)/nuclear protein localization protein 4 (NPL-4) complex, and its inhibiting co-factor P47, leading to the binding preference with the inhibitory co-factor, resulting in functional repression of VCP. This DN-VCP TG mouse provides a unique functional-inactivation model for investigating VCP in the heart in physiological and pathological conditions.

Heat shock protein 22 (Hsp22) is a small heat shock protein predominantly expressed in skeletal and cardiac muscle. Previous studies indicate that Hsp22 plays a vital role in protecting the heart against cardiac stress. However, the essential role of Hsp22 in the heart under physiological conditions remains largely unknown. In this study, we used an Hsp22 knockout (KO) mouse model to determine whether loss of Hsp22 impairs cardiac growth and function with increasing age under physiological conditions. Cardiac structural and functional alterations at baseline were measured using echocardiography and invasive catheterization in Hsp22 KO mice during aging transition compared to their age-matched wild-type (WT) littermates. Our results showed that Hsp22 deletion induced progressive cardiac dilation along with declined function during the aging transition. Mechanistically, the loss of Hsp22 impaired BCL-2–associated athanogene 3 (BAG3) expression and its associated cardiac autophagy, undermined cardiac energy metabolism homeostasis and increased oxidative damage. This study showed that Hsp22 played an essential role in the non-stressed heart during the early stage of aging, which may bring new insight into understanding the pathogenesis of age-related dilated cardiomyopathy.

We deduced that leukocyte-derived H2S would also play a pivotal role regarding nutrition homeostasis in hypertensive subjects. Plasma was obtained from patients with hypertension (n = 151) as well as control (n = 41). Leukocyte-derived H2S speed was determined, and biochemical indices of glucose and lipid metabolism were measured. Western blot analyses of CSE were also performed. Inflammation factors were measured. Leukocyte-derived H2S is produced at a significantly lower rate in overweight or obese patients (p < 0.05). There is a significant negative correlation between H2S and the levels of HOMA-RI and insulin in overweight patients and has a positive relationship with HDL-C only in overweight hypertensive patients (p < 0.05). Patients with high insulin levels showed down-regulation of CSE (p < 0.05). The levels of IL-10 decreased in both the obese and the overweight which showed significant relationship with all metabolism parameters such as HDL-C(r = 0.176, p = 0.031), insulin (r = −0.181, p = 0.027), HOMA-IR (r = −0.166, p = 0.045), and H2S speed (r = 0.995, p = 0.001). Linear regression analysis showed that insulin levels will increase (β = −1.685, p = 0.041) with the slower speed of H2S. Leukocyte-derived H2S production varied according to the nutritional status of hypertensive subjects, and the H2S/IL-10 signaling pathway may be the junction point among hypertension, disturbance of nutritional status, and inflammation.

Abstract Background Immuno-inflammation plays a major role in the process of hypertension. We aimed to evaluate the association between inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW) and all-cause mortality in elderly patients with hypertension. Methods A total of 341 hypertensive patients over 80 years of age were included to this study. The NLR and RDW were measured on admission and all the selected patients were followed up for up to 90 days. Kaplan–Meier curves were plotted to evaluate the association between the NLR and the all-cause mortality at follow-up. Using Cox regression models, we investigated the prognostic value of NLR and RDW for all-cause mortality. Results Patients with higher quartile of NLR linked to high mortality in hypertensive patients at 90 day after admission (16.47%,13.25%,1.14%,1.17% respectively; χ2 = 20.581,P = 0.000). Surviving patients had lower RDW (13.61 ± 1.37 VS 14.18 ± 1.38, p = 0.041) and NLR (4.97 ± 5.72 VS 7.95 ± 6.88,p = 0.011). The receiver operating curve (ROC) of the NLR for all-cause mortality had an area under the curve (AUC) =0.714 (95%CI: 0.629–0.798, P = 0.000), with acritical value of 2.97, with sensitivity of 92.6%, and a specificity of 52.5%. The ROC of the RDW to predict all-cause mortality, had an AUC =0.654 (95%CI:0.548–0.761, P = 0.008), with acritical value of 13.2%.The Kaplan–Meier curve showed a significant difference between different NLR levels (p = 0.002). Multivariate Cox proportional hazard analysis shown 3rd quartile of NLR(RR = 9.646, 95% CI 1.302–34.457, P = 0.041) and 4th quartiles(RR = 16.451, 95% CI 2.137–66.643, P = 0.007) were found to independently predict all-cause death in hypertensive patients over 80 years of age. Higher rank of NLR was link to higher incidence of all-cause death for such patients. Conclusion The findings of the present study demonstrate the potential utility of NLR in risk stratification of elderly patients with hypertension to provide information for clinical treatment strategies.

SMYD3 plays a key role in cancer cell viability, adhesion, migration and invasion. SMYD3 promotes formation of inducible regulatory T cells and is involved in reducing autoimmunity. However, the nearly “closed” substrate-binding site and poor in vitro H3K4 methyltransferase activity have obscured further understanding of this oncogenically related protein. Here we reveal that SMYD3 can adopt an “open” conformation using molecular dynamics simulation and small-angle X-ray scattering. This ligand-binding-capable open state is related to the crystal structure-like closed state by a striking clamshell-like inter-lobe dynamics. The two states are characterized by many distinct structural and dynamical differences and the conformational transition pathway is mediated by a reversible twisting motion of the C-terminal domain (CTD). The spontaneous transition from the closed to open states suggests two possible, mutually non-exclusive models for SMYD3 functional regulation and the conformational selection mechanism and allostery may regulate the catalytic or ligand binding competence of SMYD3. This study provides an immediate clue to the puzzling role of SMYD3 in epigenetic gene regulation.

Mitochondria undergo structural and functional remodeling to meet the cell demand in response to the intracellular and extracellular stimulations, playing an essential role in maintaining normal cellular function. Merging evidence demonstrated that dysregulation of mitochondrial remodeling is a fundamental driving force of complex human diseases, highlighting its crucial pathophysiological roles and therapeutic potential. In this review, we outlined the progress of the molecular basis of mitochondrial structural and functional remodeling and their regulatory network. In particular, we summarized the latest evidence of the fundamental association of impaired mitochondrial remodeling in developing diverse cardiac diseases and the underlying mechanisms. We also explored the therapeutic potential related to mitochondrial remodeling and future research direction. This updated information would improve our knowledge of mitochondrial biology and cardiac diseases’ pathogenesis, which would inspire new potential strategies for treating these diseases by targeting mitochondria remodeling.

Quaternary chalcogenide Cu2CdSnSe4 distributed with ex-situ homogeneous nanoinclusions has been synthesized by ball milling, followed by spark plasma sintering. The Cu2CdSnSe4 nanocrystallites with sizes ranging from 20 to 30 nm were prepared via colloidal synthesis, while the Cu2CdSnSe4 matrix was made by the traditional solid state reaction method. It is found that nanocrystallite inclusions strongly enhance electrical conductivity while preserving the Seebeck coefficient. In addition, these inclusions significantly reduce the lattice thermal conductivity through scattering phonons with all-scale length due to the polymorphous structure feature of Cu2CdSnSe4 composites. These concomitant effects result in an enhanced thermoelectric performance with the dimensionless figure of merit ZT reaching a peak value of 0.5 at 760 K, which is a 65% improvement compared to that of the pure Cu2CdSnSe4 matrix. These observations demonstrate an exciting scientific opportunity to raise the figure of merit via ex-situ homogeneous nanoinclusions, not only for quaternary chalcogenides but also for other promising thermoelectric materials.

Endoplasmic reticulum (ER) and mitochondrion are the key organelles in mammal cells and play crucial roles in a variety of biological functions in both physiological and pathological conditions. Valosin-containing protein (VCP), a newly identified calcium-associated ATPase protein, has been found to be involved in both ER and mitochondrial function. Impairment of VCP, caused by structural mutations or alterations of expressions, contributes to the development of various diseases, through an integrating effect on ER, mitochondria and the ubiquitin–proteasome system, by interfering with protein degradation, subcellular translocation and calcium homeostasis. Thus, understanding the role and the molecular mechanisms of VCP in these organelles brings new insights to the pathogenesis of the associated diseases, and leads to the discovery of new therapeutic strategies. In this review, we summarized the progress of studies on VCP, in terms of its regulation of ER and mitochondrial function and its implications for the associated diseases, focusing on the cancers, heart disease, and neurodegenerative disorders.

Tylototriton anhuiensis (Salamandridae, Urodela), collected from Yaoluoping Nature Reserve, was identified as a new species. The complete mitogenome sequence of T. anhuiensis is 16,259 by in length, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and D-loop region. The base composition of the mitogenome was 33.6%A, 26.3% C, 14.5% G, and 25.6% T. The ND6 subunit gene and eight tRNA genes were encoded on the L-strand, the others were encoded on the H-strand.

SMYD proteins are an exciting field of study as they are linked to many types of cancer-related pathways. Cardiac and skeletal muscle development and function also depend on SMYD proteins opening a possible avenue for cardiac-related treatment. Previous crystal structure studies have revealed that this special class of protein lysine methyltransferases have a bilobal structure, and an open-closed motion may regulate substrate specificity. Here we use the molecular dynamics simulation to investigate the still-poorly-understood SMYD2 dynamics. Cross-correlation analysis reveals that SMYD2 exhibits a negative correlated inter-lobe motion. Principle component analysis suggests that this correlated dynamic is contributed to by a twisting motion of the C-lobe with respect to the N-lobe and a clamshell-like motion between the lobes. Dynamical network analysis defines possible allosteric paths for the correlated dynamics. There are nine communities in the dynamical network with six in the N-lobe and three in the C-lobe, and the communication between the lobes is mediated by a lobe-bridging β hairpin. This study provides insight into the dynamical nature of SMYD2 and could facilitate better understanding of SMYD2 substrate specificity.

Hollow noble metal nanoparticles have excellent performance not only in surface catalysis but also in optics. In this work, the hollow Au–Ag alloy nanorices are fabricated by the galvanic replacement reaction. The dark-field spectrum points out that there is a big difference in the optical properties between the pure Ag nanorices and the hollow alloy nanorices that exhibit highly tunable localized surface plasmon resonances (LSPR) and that possess larger radiative damping, which is also indicated by the finite element method. Furthermore, the surface enhanced Raman scattering (SERS) and oxidation test indicate that hollow Au–Ag alloy nanorices show good anti-oxidation and have broad application prospects in surface-plasmon-related fields.