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Abstract Objective The International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system for endometrial cancer (EC) was released with incorporating histology, lympho-vascular space invasion, and molecular classification together. Our objective is to further explore the clinical utility and prognostic significance of the 2023 FIGO staging system in China. Methods A retrospective analysis was conducted for patients who received standard surgeries and underwent genetic testing using multigene next-generation sequencing (NGS) panels between December 2018 and December 2023 at Fudan University Shanghai Cancer Center, Shanghai, China. The genomic and clinical data of all patients were analyzed, and stages were determined by both the 2009 and 2023 FIGO staging systems. Kaplan–Meier estimators and Cox proportional hazards models were used for survival analysis. Results A total of 547 patients were enrolled in the study. After the restaged by the FIGO 2023 staging system, stage shifts occurred in 147/547 (26.9%) patients. In patients with early stages in FIGO 2009 (stage I-II), 63 cases were rearranged to IAmPOLEmut and 53 cases to IICmp53abn due to the molecular classification of POLEmut and p53abn. Altogether 345 cases were in stage I, 107 cases in stage II, 69 cases in stage III, and 26 cases in stage IV according to the FIGO 2023 staging criteria. For stage I diseases, the 3-year PFS rate was 92.7% and 95.3% in 2009 and 2023 FIGO staging systems, respectively. The 3-year PFS of stage II in 2023 FIGO was lower than that of FIGO 2009 (3-year PFS: 85.0% versus 90.9%), especially in substage IIC and IICmp53abn. Three cases (12%) of stage IIIA in FIGO 2009 were shifted to stage IA3 FIGO 2023, with 3-year PFS rates of 90.9% versus 100%, respectively. In NGS analysis, the most prevalent gene alterations were observed in PTEN and PIK3CA. Conclusion The FIGO 2023 staging system was proved to be a good predictor of survival for EC patients with enhanced precision compared to FIGO 2009. Predominant stage shifts were observed in early-stage diseases. Distinct gene alterations of different subtypes may help to explore more accurate target therapies.

ABSTRACT Aims/Introduction To analyze the association between HbA1c level and the risk of all‐cause mortality in community patients with type 2 diabetes mellitus, and to provide a scientific basis for the management of type 2 diabetes mellitus in the community. Materials and Methods Based on a Zhejiang rural community type 2 diabetes mellitus cohort, a total of 10,310 patients with type 2 diabetes mellitus with complete baseline and follow‐up data were selected. The Cox proportional hazards regression model and the restricted cubic spline model were used to evaluate the relationship between the HbA1c level and the risk of all‐cause mortality. Results During a mean follow‐up of 5.5 years, 971 patients died. With HbA1c levels of 6.5–7.0% as the reference, after adjusting for relevant confounding factors, the HR(95%CI) of all‐cause mortality with HbA1c levels of 0.05). Conclusions The HbA1c levels were associated with the risk of all‐cause mortality in type 2 diabetes mellitus in a “J‐shaped” manner, a too high or a too low HbA1c level could increase the risk of death. Attention should be paid to the individual evaluation of patients and the setting of appropriate glycemic control goals.

Abstract Caustics occur in diverse physical systems, spanning the nano-scale in electron microscopy to astronomical-scale in gravitational lensing. As envelopes of rays, optical caustics result in sharp edges or extended networks. Caustics in structured light, characterized by complex-amplitude distributions, have innovated numerous applications including particle manipulation, high-resolution imaging techniques, and optical communication. However, these applications have encountered limitations due to a major challenge in engineering caustic fields with customizable propagation trajectories and in-plane intensity profiles. Here, we introduce the “compensation phase” via 3D-printed metasurfaces to shape caustic fields with curved trajectories in free space. The in-plane caustic patterns can be preserved or morphed from one structure to another during propagation. Large-scale fabrication of these metasurfaces is enabled by the fast-prototyping and cost-effective two-photon polymerization lithography. Our optical elements with the ultra-thin profile and sub-millimeter extension offer a compact solution to generating caustic structured light for beam shaping, high-resolution microscopy, and light-matter-interaction studies.

Abstract Background Diffuse large B-cell lymphoma (DLBCL), an aggressive and heterogenic malignant entity, is still a challenging clinical problem, since around one-third of patients are not cured with primary treatment. Next-generation sequencing (NGS) technologies have revealed common genetic mutations in DLBCL. We devised an NGS multi-gene panel to discover genetic features of Chinese nodal DLBCL patients and provide reference information for panel-based NGS detection in clinical laboratories. Methods A panel of 116 DLBCL genes was designed based on the literature and related databases. We analyzed 96 Chinese nodal DLBCL biopsy specimens through targeted sequencing. Results The most frequently mutated genes were KMT2D (30%), PIM1 (26%), SOCS1 (24%), MYD88 (21%), BTG1 (20%), HIST1H1E (18%), CD79B (18%), SPEN (17%), and KMT2C (16%). SPEN (17%) and DDX3X (6%) mutations were highly prevalent in our study than in Western studies. Thirty-three patients (34%) were assigned as genetic classification by the LymphGen algorithm, including 12 cases MCD, five BN2, seven EZB, seven ST2, and two EZB/ST2 complex. MYD88 L265P mutation, TP53 and BCL2 pathogenic mutations were unfavorable prognostic biomarkers in DLBCL. Conclusions This study presents the mutation landscape in Chinese nodal DLBCL, highlights the genetic heterogeneity of DLBCL and shows the role of panel-based NGS to prediction of prognosis and potential molecular targeted therapy in DLBCL. More precise genetic classification needs further investigations.

Objective: This study aims to analyze how changes in pathological diagnosis practice and molecular detection technology have affected clinical outcomes for colorectal cancer (CRC) patients in Fudan University Shanghai Cancer Center (FUSCC). Methods: This retrospective cohort study analyzed 21,141 pathologically confirmed CRC cases diagnosed at FUSCC from 2008 to 2020. Patients were divided into five groups for different analytical purposes: (1) the before vs. since 2014 groups to analyze the influence of the changes in the classification criteria of pT3 and pT4 staging on the survival of patients; (2) the partial vs. total mesorectal excision (TME) groups to analyze whether evaluation of completeness of the mesorectum have impact on the survival of patients; (3) the tumor deposit (TD)(+)N0 vs. TD(+)N1c groups to analyze the influence of the changes in the pN staging on the survival of patients with positive TD and negative regional lymph node metastasis (LNM); (4) the before vs. since 2013 groups to analyze the influence of the changes in the testing process of deficient mismatch repair on the survival of patients; and (5) the groups with vs. without RAS/BRAF gene mutation testing to analyze the influence of these testing on the survival of patients. Patients’ clinicopathological parameters, including age at diagnosis, sex, tumor size, location, differentiation, mucinous subtype, TD, lymphovascular invasion, perineural invasion, tumor depth, LNM and distant metastasis, and tumor-node-metastasis (TNM) stage, were compared between groups. Kaplan-Meier analysis with log rank method was performed for patients’ overall survival (OS) and disease-free survival (DFS) analyses. Results: In pathological reports, there were three parameter changes that impacted patient outcomes. Firstly, changes in the pT staging criteria led to a shift of the ratio of patients with stage pT3 to stage pT4 from 1: 110.9 to 1: 0.26. In comparison to patients admitted before 2014 (n = 4,754), a significant difference in prognosis between pT3 and pT4 stages was observed since 2014 (n = 9,965). Secondly, we began to evaluate the completeness of the mesorectum since 2016. As a result, 91.0% of patients with low rectal cancer underwent TME (n = 4,111) surgery, and patients with TME had significantly better OS compared with partial mesorectal excision (PME, n = 409). Thirdly, we began to stage TD (+) LNM (-) as N1c since 2017. The results showed that N1c (n = 127) but not N0 (n = 39) can improve the prognosis of patients without LNM and distal metastasis. In molecular testing, there have been three and five iterations of updates regarding mismatch repair (MMR)/microsatellite instability (MSI) status and RAS/BRAF gene mutation detection, respectively. The standardization of MMR status testing has sharply decreased the proportion of deficient MMR (dMMR) patients (from 32.5% to 7.4%) since 2013. The prognosis of patients underwent MMR status testing since 2013 (n = 867) were significantly better than patients before 2013 (n = 1,313). In addition, detection of RAS/BRAF gene mutation status (n = 5,041) resulted in better DFS but not OS, for patients with stage I-III disease (n = 16,557). Conclusion: Over the past few decades, updates in elements in pathological reports, as well as the development of standardized tests for MMR/MSI status and RAS/BRAF gene mutations have significantly improved patient outcomes.

Angiogenesis is an essential process in tumorigenesis, tumor invasion, and metastasis, and is an intriguing pathway for drug discovery. Targeting vascular endothelial growth factor receptor 2 (VEGFR2) to inhibit tumor angiogenic pathways has been widely explored and adopted in clinical practice. However, most drugs, such as the Food and Drug Administration –approved drug axitinib (ATC code: L01EK01), have considerable side effects and limited tolerability. Therefore, there is an urgent need for the development of novel VEGFR2 inhibitors. In this study, we propose a novel strategy to design potential candidates targeting VEGFR2 using three-dimensional (3D) deep learning and structural modeling methods. A geometric-enhanced molecular representation learning method (GEM) model employing a graph neural network (GNN) as its underlying predictive algorithm was used to predict the activity of the candidates. In the structural modeling method, flexible docking was performed to screen data with high affinity and explore the mechanism of the inhibitors. Small -molecule compounds with consistently improved properties were identified based on the intersection of the scores obtained from both methods. Candidates identified using the GEM-GNN model were selected for in silico modeling using molecular dynamics simulations to further validate their efficacy. The GEM-GNN model enabled the identification of candidate compounds with potentially more favorable properties than the existing drug, axitinib, while achieving higher efficacy.

The sedimentary total organic carbon (TOC) in mangrove ecosystems plays an essential role in the global carbon storage. Nevertheless, little information is available about the pattern of TOC in sediments varying from bare and flat to those beneath mangroves. To find out the roles of new-developing mangroves in sedimentary TOC accumulation, a serials of sediment samples were collected from the creek mudflat zone (CMZ) through the fringe mangrove zone (FMZ) to the interior mangrove zone (IMZ) in young mangrove system of Nanliu River Delta in China. Sediment compositions, TOC, total nitrogen (TN), molar C/N ratios, and carbon stable isotopes (δ13C) were analyzed to examine the accumulation processes. The results revealed the distinct differences in the sedimentary TOC values, with an obvious increasing trend from the CMZ and FMZ to the IMZ. We quantified that terrestrials, marine-derived and mangrove-derived sources contributed 39.2-74.1%, 24.7-63.1% and 0.9-6.9%, respectively, to the sedimentary TOC in the mangrove ecosystems. The organic carbon accumulation rates ranged from 2.59 to 269.60 g•m-2•a-1, with values of 8.77 ± 19.87, 24.78 ± 12.53, 167.19 ± 57.79 g•m-2•a-1 for CMZ, FMZ and IMZ. Our work highlights information showing that young mangrove forests of the tropical delta have important potential for carbon storage.

Abstract Background Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. Methods and results Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival. Conclusions We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates.

Summary: Background: Both defects in mismatch repair (dMMR) and high microsatellite instability (MSI-H) have been recognised as crucial biomarkers that guide treatment strategies and disease management in colorectal cancer (CRC). As MMR and MSI tests are being widely conducted, an increasing number of MSI-H tumours have been identified in CRCs with mismatch repair proficiency (pMMR). The objective of this study was to assess the clinical features of patients with pMMR/MSI-H CRC and elucidate the underlying molecular mechanism in these cases. Methods: From January 2015 to December 2018, 1684 cases of pMMR and 401 dMMR CRCs were enrolled. Of those patients, 93 pMMR/MSI-H were identified. The clinical phenotypes and prognosis were analysed. Frozen and paraffin-embedded tissue were available in 35 patients with pMMR/MSI-H, for which comprehensive genomic and transcriptomic analyses were performed. Findings: In comparison to pMMR/MSS CRCs, pMMR/MSI-H CRCs exhibited significantly less tumour progression and better long-term prognosis. The pMMR/MSI-H cohorts displayed a higher presence of CD8+ T cells and NK cells when compared to the pMMR/MSS group. Mutational signature analysis revealed that nearly all samples exhibited deficiencies in MMR genes, and we also identified deleterious mutations in MSH3-K383fs. Interpretation: This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H. Funding: This work was supported by the Science and Technology Commission of Shanghai Municipality (20DZ1100101).

Defects in genes involved in the DNA damage response cause homologous recombination repair deficiency (HRD). HRD is found in a subgroup of cancer patients for several tumor types, and it has a clinical relevance to cancer prevention and therapies. Accumulating evidence has identified HRD as a biomarker for assessing the therapeutic response of tumor cells to poly(ADP-ribose) polymerase inhibitors and platinum-based chemotherapies. Nevertheless, the biology of HRD is complex, and its applications and the benefits of different HRD biomarker assays are controversial. This is primarily due to inconsistencies in HRD assessments and definitions (gene-level tests, genomic scars, mutational signatures, or a combination of these methods) and difficulties in assessing the contribution of each genomic event. Therefore, we aim to review the biological rationale and clinical evidence of HRD as a biomarker. This review provides a blueprint for the standardization and harmonization of HRD assessments.

ABSTRACTThis study examined the effects of two fat-to-lean ratios (7:3 and 6:4) and five cooking times (30 min, 60 min, 90 min, 120 min and 150 min) on water migration in and the nutritional quality and fatty acid composition of traditional Chinese pork meatballs. Accordingly, this work has established a quality control reference for the industrial-scale research and development of pork meatball production. Low-field nuclear magnetic resonance was used to determine the distribution and migration of water in pork meatballs during the cooking process, and gas chromatography–mass spectrometry was used to determine the fatty acid composition of pork meatballs. The results show that the water in pork meatballs migrated and thus became more strongly bound as the cooking time increased. The relaxation time of water in pork meatballs with a fat-to-lean ratio of 7:3 was significantly higher than that of water in pork meatballs with a fat-to-lean ratio of 6:4 (P .05). When the pork meatballs were cooked for 150 min, the calorie value of pork meatballs with a fat-to-lean ratio of 7:3 was significantly greater than that of pork meatballs with a fat-to-lean ratio of 6:4. The hardness and tenderness of pork meatballs with a fat-to-lean ratio of 7:3 were significantly lower than those of pork meatball with a fat-to-lean ratio of 6:4 (P

Wearable electronic devices have emerged as a pivotal technology in healthcare and artificial intelligence robots. Among the materials that are employed in wearable electronic devices, organic thermoelectric materials possess great application potential due to their advantages such as flexibility, easy processing ability, no working noise, being self-powered, applicable in a wide range of scenarios, etc. However, compared with classic conductive materials and inorganic thermoelectric materials, the research on organic thermoelectric materials is still insufficient. In order to improve our understanding of the potential of organic thermoelectric materials in wearable electronic devices, this paper reviews the types of organic thermoelectric materials and composites, their assembly strategies, and their potential applications in wearable electronic devices. This review aims to guide new researchers and offer strategic insights into wearable electronic device development.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC), which first emerged in 2012, persist and continue to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After the extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction in viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Abstract Objective We aimed to investigate the association between visit‐to‐visit heart rate variability (VVHRV) and all‐cause mortality in patients diagnosed with atrial fibrillation (AF). Previous studies have shown a positive correlation between VVHRV and several adverse outcomes. However, the relationship between VVHRV and the prognosis of AF remains uncertain. Methods In our study, we aimed to examine the relationship between VVHRV and mortality rates among 3983 participants with AF, who were part of the AFFIRM study (Atrial Fibrillation Follow‐Up Investigation of Rhythm Management). We used the standard deviation of heart rate (HRSD) to measure VVHRV and divided the patients into four groups based on quartiles of HRSD (1st,

Mesenchymal epithelial transition (MET) factor alteration in non-small cell lung cancer (NSCLC) includes MET exon 14 skipping alteration (METex14 skipping), MET gene amplification, MET gene mutation (mainly kinase domain mutation), MET gene fusion, and MET protein overexpression. The incidence of METex14 skipping in patients with NSCLC is 0.9–4.0%. At present, drugs targeting METex14 skipping have been approved in China and other countries like Japan and USA. Patients with advanced NSCLC should undergo testing, including METex14 skipping, to screen the population with benefit from targeted therapy with MET inhibitors. The incidence of de novo MET gene amplification in NSCLC patients is 1–5%, the incidence of acquired MET gene amplification in epidermal growth factor receptor tyrosine kinase inhibitor (TKI)-resistant patients is 5–50%, and the incidence in anaplastic lymphoma kinase (ALK) TKI-resistant patients is about 13%; the incidence of MET protein overexpression in NSCLC patients is 13.7–63.7%. Several clinical trials on MET gene amplification and MET protein overexpression are ongoing, which have demonstrated their important guiding significance as biomarkers in the clinical treatment with MET inhibitors. Accurate detection of MET alterations is a prerequisite for MET inhibitor therapy. Since there are many types of MET alterations and related testing methods, as well as many problems and challenges during clinical testing, further sorting and standardization are required. Combined with clinical practice experience, literature review, and expert discussion, the writing group developed this consensus on the three main types of MET alterations (METex14 skipping, MET gene amplification, and MET protein overexpression) in order to guide the practical applications of clinical MET testing.

Anhedonia is a hallmark symptom of depression that often lacks adequate interventions. The translational gap remains in clinical treatments based on neural substrates of anhedonia. Our pilot study found that depressed individuals depended less on goal-directed (GD) reward learning (RL), with reduced reward prediction error (RPE) BOLD signal. Previous studies have found that anhedonia is related to abnormal activities and/or functional connectivities of the central executive network (CEN) and salience network (SN), both of which belong to the goal-directed system. In addition, it was found that real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) could improve the balance between CEN and SN in healthy individuals. Therefore, we speculate that rt-fMRI NF of the CEN and SN associated with the GD system may improve depressive and/or anhedonic symptoms. Therefore, this study (1) will examine individuals with anhedonic depression using GD-RL behavioral task, combined with functional magnetic resonance imaging and computational modeling to explore the role of CEN/SN deficits in anhedonic depression; and (2) will utilize network-based rt-fMRI NF to investigate whether it is feasible to regulate the differential signals of brain CEN/SN of GD system through rt-fMRI NF to alleviate depressive and/or anhedonic symptoms. This study highlights the need to elucidate the intervention effects of rt-fMRI NF and the underlying computational network neural mechanisms.

AbstractIntroduction Ovarian clear cell carcinoma (OCCC) has distinct clinical and molecular features and heterogeneous prognosis. Insights into the somatic genomic abnormalities of OCCC provide the basis for deeper understanding and potential therapeutic avenues. Herein, we performed extensive genomic profiling in Chinese patients to illustrate the mutation landscape and genetic prognostic biomarkers of OCCC.Patients and methods We used targeted DNA sequencing on 61 OCCC cases with a panel of 520 cancer-related genes. Correlations between clinicopathological features and survival were evaluated. Nomogram-based models were constructed to predict progress-free survival (PFS).Results We detected 763 somatic mutations spanning 286 genes. The most frequent genetic alterations, ARID1A (49%) and PIK3CA (48%), were concurrently mutated. Comprehensive copy number alterations (CNAs) were identified in chromosomes 20q13.2 and 8q. Most (73.7%) patients harboured potentially targetable driver mutations. The mean and median tumour mutational burden were 7.0 and 3.0 mutations/Mb, respectively. Microsatellite instability (high) was identified in 8.2% of patients. Mutation of the base-excision repair pathway was significantly higher in patients of stage II/III/IV. ATM mutation was associated with platinum sensitivity (p

Abstract Human epidermal growth factor receptor 2 (HER2) gene amplification helps identify breast cancer patients who may respond to targeted anti-HER2 therapy. This study aims to develop an automated method for quantifying HER2 fluorescence in situ hybridization (FISH) signals and improve the working efficiency of pathologists. An Aitrox artificial intelligence (AI) model based on deep learning was constructed, and a comparison between the AI model and traditional manual counting was performed. In total, 918 FISH images from 320 consecutive invasive breast cancers were analysed and automatically classified into 5 groups according to the 2018 ASCO/CAP guidelines. The overall classification accuracy was 85.33% (157/184) with a mean average precision of 0.735. In Group 5, the most common group, the consistency was as high as 95.90% (117/122), while the consistency was low in the other groups due to the limited number of cases. The causes of this inconsistency, including clustered HER2 signals, coarse CEP17 signals and some section quality problems, were analysed. The developed AI model is a reliable tool for evaluating HER2 amplification statuses, especially for breast cancer in Group 5; additional cases from multiple centres could further improve the accuracy achieved for other groups.

Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury closely related to insulin resistance (IR) and genetic susceptibility without alcohol consumption, which encompasses a spectrum of liver disorders ranging from simple hepatic lipid accumulation, known as steatosis, to the more severe form of steatohepatitis (NASH). NASH can progress to cirrhosis and hepatocellular carcinoma (HCC), posing significant health risks. As a multisystem disease, NAFLD is closely associated with systemic insulin resistance, central obesity, and metabolic disorders, which contribute to its pathogenesis and the development of extrahepatic complications, such as cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and certain extrahepatic cancers. Recent evidence highlights the indispensable roles of intestinal barrier dysfunction and gut microbiota in the onset and progression of NAFLD/NASH. This review provides a comprehensive insight into the role of intestinal barrier dysfunction and gut microbiota in NAFLD, including intestinal barrier function and assessment, inflammatory factors, TLR4 signaling, and the gut–liver axis. Finally, we conclude with a discussion on the potential therapeutic strategies targeting gut permeability and gut microbiota in individuals with NAFLD/NASH, such as interventions with medications/probiotics, fecal transplantation (FMT), and modifications in lifestyle, including exercise and diet.

The pivotal role of farmers’ cropland conservation behavior (CCB) in advancing green agricultural practices is well-recognized. This paper underscores the critical role of stable land tenure in enhancing farmers’ CCB, exemplified by the practice of mulch recycling. Drawing on a survey of 349 cotton farmers in Xinjiang, Northwest China, it offers a systematic examination of how land tenure stability influences CCB and its underlying mechanisms. The findings reveal a significant positive correlation between land tenure stability and CCB. Notably, this relationship is mediated by the facilitation of land mortgages, wherein written contracts and extended land tenure durations enhance farmers’ participation in land mortgages, thereby bolstering CCB. Furthermore, the stabilizing effect of land tenure on CCB also mitigates the negative impacts of risk aversion and time preference. The study additionally highlights the differential effects of land tenure stability based on farm size and technical training; its facilitative role in CCB is more pronounced among larger-scale farmers and those engaged in technical training.

The concept of single-valued neutrosophic sets (SVNSs) is considered as an attractive tool for dealing with highly ambiguous and uncertain information. The correlation coefficient of SVNSs acts as an important measure in the single-valued neutrosophic set theory and it has been applied in various fields, such as the pattern recognition, medical diagnosis, decision-making and also clustering analysis. To alleviate the weakness of the existing correlation coefficients, a novel statistical correlation coefficient is put forward to measure the degree of correlation between two SVNSs. This statistical correlation coefficient is developed based on the variance and covariance of SVNSs and its value is between −1 and 1. When solving the multicriteria decision making problems, the criteria show different weight values. To consider the weight information of multiple criteria, the weighted statistical correlation coefficient is developed for SVNSs. Afterwards, two numerical examples are given to show the effectiveness of the proposed statistical correlation coefficient in the pattern recognition, which can accurately classify unknown patterns into known patterns. Finally, the feasibility and practicability of the proposed correlation coefficient formula are illustrated by a practical multiple attribute decision making problem of traditional Chinese medicine diagnosis. The comparative results show that the proposed correlation coefficient formula is rational and effective.

Ultrasound on livestock and poultry meat products processing mainly through ultrasound generated cavitation and other effects, so that the meat structure, nutrients, flavour substances and other changes, so as to have an impact on its quality. A new technique for cooking is ultrasonic assistance. When compared to the traditional way of cooking, its benefits of high frequency and high calories can quickly enhance the efficiency of food preparation, achieving greater results than the traditional long-term cooking effect in a short period of time. This study analyzes the function of ultrasonic assisted cooking in the quality processing of livestock and poultry meat products based on ultrasonic assisted cooking and integrated with the research development at home and abroad. It serves as a theoretical underpinning for the subsequent industrial production and healthy diet of food cattle and poultry meat products, and contributes positively to the future direction of food production and processing.

Despite the large demand, the current biomass composites still exhibit problems of low mechanical properties, strong hydrophilicity, and poor thermal resistance, which limit biomass composites' application fields. Facing these problems, starch-based fiber-reinforced composites with foam structures were fabricated by hot pressing and foaming process, for the first time. In these composites, the corn starch serves as matrix while the sisal fiber acts as skeleton. Aluminum hydroxide (ATH) has been added to alter microstructures. To identify microstructure and material composition changes induced by ATH, scanning electron microscopy, X-ray diffraction analysis, and Fourier transform infrared spectroscopy have been performed. Experimental results show that an appropriate ATH content can improve composite's ultimate tensile strength by as much as 37%. Molecular dynamic simulations were performed to understand ATH effects on tensile properties at an atomic level. In addition to tensile properties, the addition of ATH is also beneficial to improve the compressive properties, water resistance and thermal stability of starch-based fiber-reinforced composites, making the composite a potential candidate to replace traditional packaging materials. Therefore, this investigation will benefit the current packaging industry in that sustainable utilization of packaging materials can be realized.

Sugar transporters (STs) play a crucial role in the development of maize kernels. However, very limited information about STs in maize is known. In this study, sixty-eight ZmST genes were identified from the maize genome and classified into eight major groups based on phylogenetic relationship. Gene structure analysis revealed that members within the same group shared similar exon numbers. Synteny analysis indicated that ZmSTs underwent 15 segmental duplication events under purifying selection. Three-dimensional structure of ZmSTs demonstrated the formation of a compact helix bundle composed of 8–13 trans-membrane domains. Various development-related cis-acting elements, enriched in promoter regions, were correlated with the transcriptional response of ZmSTs during kernel development. Transcriptional expression profiles exhibited expression diversity of various ZmST genes in roots, stems, leaves, tassels, cobs, embryos, endosperms and seeds tissues. During kernel development, the expression of 24 ZmST genes was significantly upregulated in the early stage of grain filling. This upregulation coincided with the sharply increased grain-filling rate observed in the early stage. Overall, our findings shed light on the characteristics of ZmST genes in maize and provide a foundation for further functional studies.

Abstract Background Cancer of unknown primary (CUP) is defined the presence of metastatic disease without an identified primary site. An unidentifiable primary site of cancer creates significant challenges for treatment selection. We aimed to describe the clinicopathological, molecular, and prognostic characteristics of Chinese CUP patients. Methods Patients with oncologist‐confirmed CUP were identified at Fudan University Shanghai Cancer Center from 2019 to 2020. Information on patient characteristics, tumor presentation, treatment, and outcome were retrospectively collected from the inpatient database and pathological consultation database for descriptive analysis. A multivariable logistic regression model was established to identify factors associated with patient prognosis. Results A total of 1420 CUP patients were enrolled in this study. The baseline characteristics of the entire cohort included the following: median age (59 years old), female sex (45.8%), adenocarcinoma (47.7%), and poorly differentiated or undifferentiated tumors (92.1%). For the inpatient cohort, the most common sites where cancer spread included the lymph nodes (41.8%), bone (22.0%), liver (20.1%), and peritoneum/retroperitoneum (16.0%). A total of 77.4% and 58.2% of patients were treated with local therapy and systemic therapy, respectively. Four prognostic factors, including liver metastasis, peritoneal/retroperitoneal metastasis, number of metastatic sites (N ≥ 2), and systemic treatment, were independently associated with overall survival. Additionally, 24.8% (79/318) of patients received molecular testing, including PD‐L1, human papillomavirus, genetic variation, and 90‐gene expression tests for diagnosis or therapy selection. Conclusion Cancer of unknown primary remains a difficult cancer to diagnose and manage. Our findings improve our understanding of Chinese CUP patient characteristics, leading to improved care and outcomes for CUP patients.

Abstract Background Breast cancer patients of American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) Group 2 were all HER2-negative according to the 2018 guideline, not HER2-positive as defined in the 2013 guideline. Methods We aims to elucidate the unique clinicopathological features of ASCO/CAP Group 2 patients by comparing with classic HER2-nonamplified cancers, and reveal the efficacy of the former to anti-HER2 therapy. The clinicopathological features, treatment and prognosis information of 99 patients between 2014 and 2018 were collected. HER2 status was re-defined using the updated recommendations. Results Of the 99 ASCO/CAP Group 2 tumors, 25.5% (25/99) tumors were immunohistochemical (IHC) 0/1+ and 74.7% (74/99) tumors were IHC 2+. According to the updated 2018 guideline, all of them were HER2 negative. When compared to ASCO/CAP Group 5, patients of ASCO/CAP Group 2 displayed higher ratio of histological grade 3 (P = .03), high Ki67 proliferation index (P = .03) and pN3 (more than 9 lymph nodes metastasis, P = .02), and lower estrogen receptor (ER) positivity (P = .04). There was no statistical difference in the survival of patients received anti-HER2 therapy and patients not received anti-HER2 therapy. Conclusions Patients of ASCO/CAP Group 2 did not received apparent benefit from anti-HER2 treatment. Although according to the updated guidelines and latest reports, HER2 is negative, but when compared with classic HER2-nonamplified cancers, patients of this group seemed to be more aggressive. We suggest that this group still be regarded as an independent category, in order to accumulate more cases in the future to expand the scope of research.

Abstract Background The concept of employability can help educators understand the variability in the career outcome of graduates. Within the health professional education (HPE) literature, various conceptions of employability are used and implied. This review considers how the concept ‘employability’ is depicted and characterised in HPE literature. Methods A scoping review was conducted. The authors searched Medline, Web of Science and Scopus databases for English language literature relevant to employability in HPE. Arksey and O'Malley’s review protocol and the criteria defined in the preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews Checklist (PRISMA-ScR) were used with methodological guidance provided by Levac et al. and Peters et al. with the exception of formal stakeholder consultation. Results The search resulted in 158 articles, of which 34 articles were included in this review. Charting the included articles revealed that within the set of articles, there is much diversity in study design, geographical setting and health profession. Three conceptions of employability were identified: acquiring a professional job, sustaining employment and thriving in the workforce. Conclusion Conceptions of employability in HPE are largely focused on listing skills and capabilities for entry into employment and sustaining a career. To address gaps in research, structural contributions to employability and institutional strategies to promote conditions for thriving in disruption should be explored.

Objective: The data regarding the mutation landscape in Chinese patients with thyroid cancer are limited. The diagnostic performance of thyroid nodul es by fine-needle aspiration (FNA) cytology needs optimization, especially in indeterminate nodules. Methods: A total of 1039 FNA and surgical resection samples tested using the targeted multigene next-generation sequencing (NGS) panel were retrospectively collected. The features of gene alterations in different thyroid tumors wer e analyzed, and the diagnostic efficacy was evaluated. Results: Among 1039 samples, there were 822 FNA and 217 surgical FFPE samples. Among 207 malignant thyroid resections, a total of 181 out of 193 papillary thyroid carcinomas (PTCs) were NGS-positive (93.8%), with a high prevalence of BRAF mutations (81.9%, 158/193) and a low prevalence of RAS (1.0%, 2/193) and TERT promoter mutations (3.6%, 7/193). Gene fusions, involving the RET and NTRK3 genes, were present in 20 PTCs (10.4%) and mutually exclusive with other driver mutations. Two of three follicular thyroid carcinomas harbored multiple mutations. RET gene point mutations were common in medullary thyroid carcinoma (8/11, 72.7%). The combination of cytology and DNA–RNA-based NGS analysis demonstrated superior diagnostic value (98.0%) in FNA samples. For indeterminate thyroid nodules, the diagnostic sens itivity and specificity of NGS testing were 79.2 (38/48) and 80.0% (8/10), respectively. Two mutation-positive benign cases harbored NRAS and TSHR mutations, respectively. Conclusions: Our study revealed the distinct molecular profile of thyroid tu mors in the Chinese population. The combination of NGS testing and FNA cytology could facilitate the accurate diagnosis of thyroid nodules, especially for indeterminate nodules.

Background: Homologous Recombination Repair (HRR) is the most reliable and important signaling pathway for repairing DNA damage. We initiated a calibration project to better understand the NGS landscape for HRR gene testing in China, provide indications for testing standardization, and guide clinical practice. Methods: A questionnaire was used to collect laboratory information, panel design for HRR gene testing, tissue sample test parameters, plasma ctDNA sample test parameters, and procedures for variant interpretation. The testing quality of the participating laboratories was further evaluated by external quality assessment (EQA), which provided 5 FFPE slices and 5 mimic ctDNA samples as standard references for evaluation. Test results and reports were collected to assess laboratory performance. Results: Our results showed that different laboratories had significant differences in sequencing platforms, library construction technologies, genes in the testing panel, detectable mutation types, probe coverage regions, sequencing parameters, variants interpretation guidelines, and positive test rates. For the EQA test, the overall pass rate was about 60%. The average accuracy for tissue samples and ctDNA samples was 79.55% and 74.13%, respectively. It is worth noting that variants in tandem repetition regions and splice sites, and those with low allele frequency were more prone to misdetection. The most common reasons for misdetection were as follows: the testing panel did not cover the genes or the whole exon and splice sites of the genes; the variants were misclassified as benign or likely benign, and the variants failed the QC criteria. Conclusions: The discrepancies observed in our survey and EQA test affect the authenticity of HRR gene test results for prostate cancer, underlining the need to establish guidelines for HRR gene testing and variant interpretation in China, and to optimize HRR gene testing in clinical practice to improve management and patient care.

The effect of freeze-thaw cycling on the quality of pre-fermented red bean steamed bun (RBSB) dough and the cooked product were explored. For frozen dough samples, the changes in water distribution, frozen water content, starch crystallinity, layered structure, and protein secondary structure of the dough during freeze-thaw cycling were analyzed. The textures, colors, and relative amino acids contents of RBSBs, which were steamed from frozen dough, were analyzed. The results showed that the transverse relaxation time of weakly bound water,T22,increased as the number of freeze–thaw cycles increased, and the freezable water content reached its highest value (14.68%) after 1 cycle. The relative crystallinity of starch was increased by 13.6% compared with the control after 4 freeze-thaw cycles. The lamellar structure of starch increased by 4.33% after more than 5 freezing cycles. Freeze-thaw treatments caused significant and irregular changes in the secondary structure of the frozen dough. Freeze-thaw cycling accelerated an increase in the hardness of RBSB products. The brightness (L*) of RBSBs decreased significantly with increases in the number of freeze-thaw cycles, and these cycles also affected the amino acid contents of RBSBs.

The construction of semiconductor heterojunction photocatalysts that improve the separation and transfer of photoinduced charge carriers is an effective and widely employed strategy to boost photocatalytic performance. Herein, we have successfully constructed a CdS/Ag/Bi2WO6 Z-scheme heterojunction with an Ag-bridge as an effective charge transfer channel by a facile process. The heterostructure consists of both CdS and Ag nanoparticles anchored on the surface of Bi2WO6 nanosheets. The photocatalytic efficiency of the CdS/Ag/Bi2WO6 system was studied by the decontamination of tetracycline (TC) and Rhodamine B (RhB) under visible light irradiation (λ ≥ 420). The results exhibited that CdS/Ag/Bi2WO6 shows markedly higher photocatalytic performance than that of CdS, Bi2WO6, Ag/Bi2WO6, and CdS/Bi2WO6. The trapping experiment results verified that the •O2− and h+ radicals are the key active species. The results of photoluminescence spectral analysis and photocurrent responses indicated that the CdS/Ag/Bi2WO6 heterojunctions exhibit exceptional efficiency in separating and transferring photoinduced electron−hole pairs. Based on a series of characterization results, the boosted photocatalytic activity of the CdS/Ag/Bi2WO6 system is mostly due to the successful formation of the Ag-bridged Z-scheme heterojunction; these can not only inhibit the recombination rate of photoinduced charge carriers but also possess a splendid redox capacity. The work provides a way for designing a Z-scheme photocatalytic system based on Ag-bridged for boosting photocatalytic performance.

Material extrusion (ME) is considered as an effective and economic method to process continuous carbon fiber (CCF)-reinforced polymer composites with complicated structures. In this investigation, water absorption tests and tensile tests were conducted on ME-printed CCF-reinforced polymer composites under hydrothermal conditions. The purpose is to meet the growing need of CCF-reinforced polymer composites for high-humidity and high-heat aerospace applications. In order to achieve optimal comprehensive performance, both the L16 (45) orthogonal array method and the fuzzy reasoning algorithm were employed to carry out multi-objective optimization of four selected input variables, including layup angle, nozzle temperature, fiber filling density, and layer thickness. Experimental results show that the comprehensive performance of composites obtained by inputting data into the fuzzy reasoning system was greater than that obtained from orthogonal test results. Specifically, the optimized input variables are 0° layup angle, 260 °C nozzle temperature, 80% fiber filling rate, and 0.6 mm layer thickness.

Abstract Background The COVID-19 pandemic challenged all healthcare providers including dental practitioners. This cross-sectional study aimed to investigate the dental practitioners’ perceptions and attitudes towards the impacts of COVID-19 on their professional practice, career decision and patient care. Methods Data was collected from dental practitioners registered in New South Wales (NSW), Australia using an online survey. Results and conclusion Responses received from 206 dental practitioners revealed their perceptions and attitudes towards COVID-19 infection risk, clinical guidelines, and measures adopted to deliver patient care. Majority of participants perceived the risk of infection in dentistry was higher compared with other health professionals. Most dental practices have followed guidelines received from professional associations and adopted multiple measures such as providing hand sanitizer, social distancing, and risk screen, to ensure safe delivery of oral health care. Over 80% of dental practitioners raised concerns on patients’ accessibility to dental care during the pandemic. Despite tele-dentistry was introduced, almost half of the participants did not recognize tele-dentistry as an effective alternative. Moreover, negative impacts of COVID-19 pandemic on dental practitioner’s professional career have been reported, including lower practice safety, reduction in working hours and income. Noteworthy, one quarter of participants even considered changing their practice environment, moving sectors or even leaving their career in dentistry. However, majority of the dental practitioners are willing to stay in their current practice environment and continue their career in dentistry. Our observations demonstrate the systematic disruption to dental practice faced in Australia due to the COVID-19 pandemic. Providing dental practitioners with timely educational training and support is important to minimise negative impacts of the challenges and to optimise dental care.

Abstract With the continuous improvement in the resolution of synthetic aperture radar (SAR), there are many problems in the interpretation of high-resolution SAR images, such as a large amount of data and low efficiency of target recognition. In this paper, a novel SAR target recognition method based on a two-dimensional bidirectional principal component cooperative representation projection feature ((2D)2PCA-CRP) is proposed. First, (2D)2PCA is used to project the image into the low-dimensional feature space, and the redundant information in the high-resolution SAR image is filtered while considering the spatial structure. Then, the spatial global separability feature and local structure feature of the target in the high-resolution SAR image are extracted by CRP to form the (2D)2PCA-CRP feature. Finally, based on this feature, the nearest neighbour classifier is used to complete the target recognition experiments on MSTAR data. The experiments of this study are divided into three parts using standard operation condition (SOC) samples, type change samples and radar incidence angle change data. The experimental results show that the proposed feature achieves better target recognition performance in high-resolution SAR images.

Abstract Genetic abnormalities in histone methyltransferases (HMTs) frequently occur in diffuse large B-cell lymphoma (DLBCL) and are related to its progression. SET and MYND domain containing 3 (SMYD3) is an HMT that is upregulated in various tumors and promotes their malignancy. However, to the best of our knowledge, the function of SMYD3 in DLBCL has not been investigated thus far. In the present study, 22 HMT genes related to cancer development were first selected according to current literature, and it was found that high SMYD3 expression was significantly associated with poor progression-free survival in patients with DLBCL. SMYD3 protein levels were upregulated and positively associated with poor prognosis and poor responsiveness to chemotherapy in patients with DLBCL. Functional examinations demonstrated that SMYD3 increased cell proliferation and the flux of aerobic glycolysis in DLBCL cells in vitro and in vivo and decreased cell sensitivity to doxorubicin in vitro. Moreover, SMYD3 could directly bind to specific sequences of Pyruvate Kinase M2 (PKM2) and promote DLBCL cell proliferation and aerobic glycolysis via H3K4me3-mediated PKM2 transcription. Clinically, SMYD3 expression positively correlated with that of PKM2, and high SMYD3 was significantly associated with high maximum standardized uptake value (SUVmax) detected by [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (PET/CT) in DLBCL samples. Concomitant expression of SMYD3 and PKM2 positively correlated with poor progression-free and overall survival in patients with DLBCL and may serve as novel biomarkers in DLBCL.

Abstract Good safety, high interfacial compatibility, low cost, and facile processability make polymer‐based solid electrolytes promising materials for next‐generation batteries. Key issues related to polymer‐based solid electrolytes, such as synthesis methods, ionic conductivity, and battery architecture, are investigated in past decades. However, mechanistic understanding of the ionic conduction is still lacking, which impedes the design and optimization of polymer‐based solid electrolytes. In this review, the ionic conduction mechanisms and optimization strategies of polymer‐based solid electrolytes, including solvent‐free polymer electrolytes, composite polymer electrolytes, and quasi‐solid/gel polymer electrolytes, are summarized and evaluated. Challenges and strategies for enhancing the ionic conductivity are elaborated, while the ion‐pair dissociation, ion mobility, polymer relaxation, and interactions at polymer/filler interfaces are highlighted. This comprehensive review is especially pertinent for the targeted enhancement of the Li‐ion conductivity of polymer‐based solid electrolytes.

ObjectiveEvidence of spatial disparity in dementia mortality in China has been found to have higher dementia mortality in eastern and rural China. Regional factors of physical and social features may be influencing this spatial disparity. However, the extent of spatial difference in dementia mortality across small regional localities is unclear. This study aims to investigate the geographic variations in mortality and risk of all dementia subtypes and identify the effect of the associated environmental risk factors.MethodsWe used surveillance data on death reports from Alzheimer’s disease and other forms of dementia in Zhejiang province from 2015 to 2019. We estimated the relative risk of dementia mortality using a Bayesian spatial model. We mapped predicted relative risk to visualize the risk of death from different types of dementia and to identify risk factors associated with dementia.ResultsThirty thousand three hundred and ninety-eight deaths attributable to dementia as the underlying or related cause (multiple causes) were reported during 2015–2019. Counties and districts in the southeast and west of Zhejiang province had significantly higher standardized mortality ratios than others. Counties and districts with a smaller proportion of residents aged 60 years or older, poorer economic status, insufficient health resources, and worse pollution had a higher risk of deaths due to dementia.ConclusionHigher risks of dementia mortality were found in counties and districts with poorer economic status, insufficient health resources, and worse pollution in Zhejiang. Our study adds new evidence on the association between socioeconomic and environmental factors and the mortality risk due to dementia.

Introduction Postpartum contraception is essential to preventing unintended pregnancies and short interpregnancy intervals. The first year after childbirth is a critical period with a high risk of unintended pregnancy and induced abortion. However, the postpartum contraceptive services are weak in China’s existing maternal and child healthcare system. We propose to evaluate the effects of integrating postpartum contraceptive services into the existing perinatal care system via a cluster randomised controlled trial.Methods and analysis This cluster randomised controlled trial involves all 13 communities of Minhang District, Shanghai, China. Communities will be randomly allocated, seven in the intervention group and six in the control group. One thousand and three hundred women, 100 women in each community, will be recruited in the study. Women assigned to the intervention group will receive postpartum contraceptive education and counselling during pregnancy, childbirth hospitalisation, postpartum home visits and the 42-day postpartum clinic check-up. Women in the control group will receive routine antenatal and postpartum care. Participants will be recruited in the first trimester during pregnancy and followed up to 1 year postpartum. The primary outcome is the incidence of unintended pregnancy within 1 year after childbirth.Ethics and dissemination The trial received ethical approval from the Ethics Committee of Shanghai Minhang District Maternal and Child Health Care Hospital (#[2020]KS-02, #[2020]KS-05, #[2020]KS-05-EX). Results will be published in academic journals and disseminated in multiple formats for the health professionals and the public.Trial registration number ChiCTR2000034603.

In recent years, the optimization of straw-rotting formulations for cultivating edible mushrooms and the management of the resulting spent mushroom substrate have emerged as new challenges. This study aimed to investigate the composting of spent mushroom substrate produced from mushroom cultivation with various straw additions, under conditions where chicken manure was also used. Parameters measured during the composting process included temperature, pH, electrical conductivity (EC), germination index (GI), moisture, and total nitrogen content. Additionally, changes in nutrient content within the compost piles before and after composting were determined, and the variations in bacterial and fungal communities across different treatments before and after composting were analyzed using 16S rRNA and ITS sequencing. The results indicated that the spent mushroom substrate produced by adding 20% straw during mushroom cultivation was more suitable for composting treatment. The findings suggest that incorporating an appropriate amount of straw in mushroom cultivation can facilitate subsequent composting of spent mushroom substrate, providing an effective strategy for both environmental protection and cost reduction.

Abstract Dietary fat is an important part of human diet and has a close relationship with human health. However, it is still unclear how gut microbiota in adolescent responds to dietary fats at a normal dose. In this study, fat-free group (BC) was used as blank control group, we explored blood index and gut microbiota structure in growing rat(aged 1 months) after feeding a normal dose of 16.9% stewed lard(SL), refined lard(RL), fish oil(FO) and soybean oil(SO) for 6 weeks, respectively. The results showed that compared with RL group, SL group showed reduced fasting blood sugar and blood lipid levels and improved nutrient absorption capacity of the intestine. The blood indexes of glucose (Glu), total cholesterol (TC) and total triglyceride (TG) in FO treatment group were relatively low. The abundance of Bacteroidetes in the BC group decreased, and the abundance of Firmicutes increased. The Firmicutes/Bacteroidetes ratio of the FO group was relatively low, and the Firmicutes/Bacteroidetes ratio of the SL group and the SO group was lower than that of the RL group. The abundance of Bacteroidaceae in the SL group was increased. Research results showed that fat-free diets will increase the risk of obesity to a certain extent; compared with refined lard, stewed lard, soybean oil and fish oil can reduce the risk of obesity to a certain extent. The present study could find that the addition and types of dietary fat will affect the abundance and diversity of rat intestinal flora, and provide some information for nutritional evaluation about these dietary lipids.

Precise control of the microstructure of nanomaterials is of interest but living lateral growth of cylinders is still very challenging. Here, the authors propose a crystallization-driven fusion-induced particle assembly strategy to prepare cylinders with growing diameters by controlled fusion of spherical micelles self-assembled from an amphiphilic homopolymer.

Abstract Surface defects (SDs) and subsurface defects (SSDs) are the key factors decreasing the laser damage threshold of optics. Due to the spatially stacked structure, accurately detecting and distinguishing them has become a major challenge. Herein a detection method for SDs and SSDs with multisensor image fusion is proposed. The optics is illuminated by a laser under dark field condition, and the defects are excited to generate scattering and fluorescence lights, which are received by two image sensors in a wide-field microscope. With the modified algorithms of image registration and feature-level fusion, different types of defects are identified and extracted from the scattering and fluorescence images. Experiments show that two imaging modes can be realized simultaneously by multisensor image fusion, and HF etching verifies that SDs and SSDs of polished optics can be accurately distinguished. This method provides a more targeted reference for the evaluation and control of the defects of optics, and exhibits potential in the application of material surface research.

Abstract Background Once malignancy tumors were diagnosed, the determination of tissue origin and tumor type is critical for clinical management. Although the significant advance in imaging techniques and histopathological approaches, the diagnosis remains challenging in patients with metastatic and poorly differentiated or undifferentiated tumors. Gene expression profiling has been demonstrated the ability to classify multiple tumor types. The present study aims to assess the performance of a 90-gene expression test for tumor classification (i.e. the determination of tumor tissue of origin) in real clinical settings. Methods Formalin-fixed paraffin-embedded samples and associated clinicopathologic information were collected from three cancer centers between January 2016 and January 2021. A total of 1417 specimens that met quality control criteria (RNA quality, tumor cell content ≥ 60% and so on) were analyzed by the 90-gene expression test to identify the tumor tissue of origin. The performance was evaluated by comparing the test results with histopathological diagnosis. Results The 1417 samples represent 21 main tumor types classified by common tissue origins and anatomic sites. Overall, the 90-gene expression test reached an accuracy of 94.4% (1338/1417, 95% CI: 0.93 to 0.96). Among different tumor types, sensitivities were ranged from 74.2% (head&neck tumor) to 100% (adrenal carcinoma, mesothelioma, and prostate cancer). Sensitivities for the most prevalent cancers of lung, breast, colorectum, and gastroesophagus are 95.0%, 98.4%, 93.9%, and 90.6%, respectively. Moreover, specificities for all 21 tumor types are greater than 99%. Conclusions These findings showed robust performance of the 90-gene expression test for identifying the tumor tissue of origin and support the use of molecular testing as an adjunct to tumor classification, especially to those poorly differentiated or undifferentiated tumors in clinical practice.

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

Abstract To bypass the conventional high temperature carbonization, MXene with an ultra‐high electrical conductivity and good electrochemical activity is coated on natural wood to make it a free‐standing electrode (TW). TW achieves a high electrical conductivity of 106.4 S m−1 and large capacitance of ~700 mF cm−2 at 0.5 mA cm−2. Furthermore, to overcome the low space utilization of the oversized vessels in wood which leads to a low energy density, a reconstructing strategy is used on TW to fully use the natural porous structure of wood by filling MXene aerogels in vessels. Compared with TW, the MXene aerogel‐loaded TW shows higher electrical conductivity of 323.6 S m−1 and capacitance of 930 mF cm−2 with remarkably high rate capability of 88.2% (0.5–10 mA cm−2). Additionally, an all‐wood eco‐supercapacitor is fabricated, and achieves a high energy density of 23 μW h cm−2 at 577 μW cm−2.

Abstract The effect of glycolysis remains largely elusive in acute T lymphoblastic leukemia (T-ALL). Increasing evidence has indicated that the dysregulation of miRNAs is involved in glycolysis, by targeting the genes coding glycolysis rate-limiting enzymes. In our previous studies, we found that overexpression of the ARRB1-derived miR-223 sponge repressed T-ALL progress and reduced the expression of miR-652-5p. However, little is known about miR-652-5p on T-ALL. Here, we showed that impaired miR-652-5p expression inhibited growth, promoted apoptosis of T-ALL cells in vitro and prolonged overall survival (OS) in vivo. Based on the GO enrichment of miR-652-5p target genes, we uncovered that impaired miR-652-5p decreased glycolysis, including reduced the lactate, pyruvate, ATP level and the total extracellular acidification rate (ECAR), elevated oxygen consumption rate (OCR) in T-ALL cell lines. Mechanically, miR-652-5p targeted the 3ʹUTR of Tigar mRNA and inhibited its expression. Furthermore, the alteration of glycosis level was attributed to Tigar overexpression, consistent with the effect of impaired miR-652-5p. Additionally, Tigar suppressed the expression of PFKFB3, a glycolysis rate-limiting enzyme, in vivo and in vitro. Taken together, our results demonstrate that impaired miR-652-5p/Tigar axis could repress glycolysis, thus to slow growth of T-ALL cells, which support miR-652-5p as a novel potential drug target for T-ALL therapeutics.

Abstract Background According to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated. Methods 195 HER2 FISH-equivocal breast cancer samples were collected from 2014 to 2018. The molecular subtype was identified according to 2013 St Gallen consensus, and HER2 status was also re-determined following 2018 ASCO/CAP guideline. All samples were classified into 4 groups according to the average HER2 copy number (4.0–4.4, 4.5–4.9, 5.0–5.4, 5.5–5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed. Results 183 (93.8%) of 195 FISH-equivocal cases were classified as luminal-like subtype, while the other 12 (6.2%) were undetermined. Following 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized as HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed a positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) patients were treated with trastuzumab, but showed no difference in prognosis with those who didn’t receive targeted therapy. Conclusions In this study, all HER2 FISH-equivocal breast cancers were recategorized as HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis.

Abstract Background Amniotic fluid (AF) provides vital information on fetal development, which is also valuable in identifying fetal abnormalities during pregnancy. However, the relationship between the metabolic profile of AF in the second trimester of a normal pregnancy with several maternal–fetal parameters remains poorly understood, which therefore limits its application in clinical practice. The aim of this study was to explore the association between the metabolic profile of AF with fetal gender, maternal age, and gestational week using an untargeted metabolomics method. Methods A total of 114 AF samples were analyzed in this study. Clinical data on fetal gender, maternal age, and gestational week of these samples were collected. Samples were analyzed by gas chromatography/time-of-flight-mass spectrometry (GC-TOF/MS). Principal component analysis(PCA), orthogonal partial least square discrimination analysis(OPLS-DA) or partial least square discrimination analysis (PLS-DA) were conducted to compare metabolic profiles, and differential metabolites were obtained by univariate analysis. Results Both PCA and OPLS-DA demonstrated no significant separation trend between the metabolic profiles of male and female fetuses, and there were only 7 differential metabolites. When the association between the maternal age on AF metabolic profile was explored, both PCA and PLS-DA revealed that the maternal age in the range of 21 to 40 years had no significant effect on the metabolic profile of AF, and only four different metabolites were found. There was no significant difference in the metabolic profiles of AF from fetuses of 17–22 weeks, and 23 differential metabolites were found. Conclusions In the scope of our study, there was no significant correlation between the AF metabolic profile and the fetal gender, maternal age and gestational week of a small range. Nevertheless, few metabolites appeared differentially expressed.