A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Progress and hotspot of diet or exercise therapy in the treatment of non-alcoholic fatty liver disease.

Introduction: The primary treatment for non-alcoholic fatty liver disease (NAFLD) is modifying lifestyle through dietary or exercise interventions. In recent decades, it has received increasing attention. However, the lack of bibliometric analysis has posed a challenge for researchers seeking to understand the overall trends in this field. Methods: As of February 3rd, 2024, 876 articles on treating NAFLD through diet or exercise therapy from 2013 to 2023 had been retrieved. Two software tools, VOSviewer and CiteSpace, were utilized to analyze the growth of publications, countries, institutions, authors, journals, citations, and keywords. Additionally, the keywords with strong citation burstiness were identified to determine the changes and future trends of research hotspots in this field. Results: China had the highest number of articles, followed by the United States and South Korea. Yonsei University and Nutrients were the institutions and journals with the most significant contributions. Professor Younossi Zobair M, from the United States, is the most prolific author in this field. Through analyzing the keywords, three research hotspots were identified: research on the pathogenesis of NAFLD, research on the treatment modalities of NAFLD, and research on the risk factors and diagnosis methods of NAFLD. In recent years, the research emphasis in this field has changed, suggesting that future research will focus on two frontier keywords: "oxidative stress" and "aerobic capacity." Conclusion: In the past eleven years, the attention in this field was still rising, and the authors, journals, countries and so on had formed a considerable cooperative relationship. There were also many highly influential and productive researchers in this field. It is speculated that new research will continue around "aerobic exercise" and "oxidative stress" in the future.

Hypermethylation of Bmp2 and Fgfr2 Promoter Regions in Bone Marrow Mesenchymal Stem Cells Leads to Bone Loss in Prematurely Aged Mice.

Osteoporosis is an age-related, systemic skeletal disease that poses a significant public health challenge in contemporary society. Development at the epigenetic level is emerging as an important pathogenic mechanism of osteoporosis. Despite indications of a robust association between DNA methylation and osteoporosis development, a comprehensive understanding of the specific role of DNA methylation in osteoporosis remains limited. In this study, significant bone loss was detected at the beginning of eight weeks of age in mouse models of premature aging (SHJHhr mice). We identified a notable upregulation of DNA methyltransferase 3b/3l (Dnmt3b/l) and downregulation of ten eleven translocation dioxygenase 1 (Tet1) in bone marrow mesenchymal stem cells (BMSCs) isolated from SHJHhr mice, along with an increase in the overall 5-methylcytosine (5mC) levels. Moreover, methylation capture sequencing revealed genomic hypermethylation in SHJHhr mice BMSCs. Integrated methylome and transcriptome analyses revealed several crucial methylated genes and networks that are potentially associated with osteoporosis development. Notably, elevated methylation levels of genes linked to the Wnt signaling pathway, particularly bone morphogenetic protein 2 (Bmp2) and fibroblast growth factor receptor (Fgfr2), appeared to compromise the osteogenic differentiation potential of BMSCs. Concurrently, DNA methyltransferase inhibitors attenuated the methylation of the promoter regions of Bmp2 and Fgfr2 and rescued the osteogenic differentiation potential of the BMSCs from SHJHhr mice. In summary, our study provides novel insights into the role of DNA methylation in the development of osteoporosis and suggests promising prospects for employing epigenetic interventions to manage osteoporosis.

Automatic high-throughput and non-invasive selection of sperm at the biochemical level.

BACKGROUND: Sperm selection, a key step in assisted reproductive technology (ART), has long been restrained at the preliminary physical level (morphology or motility); however, subsequent fertilization and embryogenesis are complicated biochemical processes. Such an enormous "gap" poses tough problems for couples dealing with infertility, especially patients with severe/total asthenozoospermia . METHODS: We developed a biochemical-level, automatic-screening/separation, smart droplet-TO-hydrogel chip (BLASTO-chip) for sperm selection. The droplet can sense the pH change caused by sperm's respiration products and then transforms into a hydrogel to be selected out. FINDINGS: The BLASTO-chip system can select biochemically active sperm with an accuracy of over 90%, and its selection efficiency can be flexibly tuned by nearly 10-fold. All the substances in the system were proven to be biosafe via evaluating mice fertilization and offspring health. Live sperm down to 1% could be enriched by over 76-fold to 76%. For clinical application to patients with severe/total asthenozoospermia, the BLASTO-chip could select live sperm from human semen samples containing 10% live but 100% immotile sperm. The rates of fertilization, cleavage, early embryos, and blastocysts were drastically elevated from 15% to 70.83%, 10% to 62.5%, 5% to 37.5%, and 0% to 16.67%, respectively. CONCLUSIONS: The BLASTO-chip represents a real biochemical-level technology for sperm selection that is completely independent of sperm's motility. It can be a powerful tool in ART, especially for patients with severe/total asthenozoospermia. FUNDING: This work was funded by the Ministry of Science and Technology of China, the Ministry of Education of China, and the Shenzhen-Hong Kong Hetao Cooperation Zone.

Insulinemic and inflammatory dietary patterns show enhanced predictive potential for gestational diabetes mellitus risk.

CONTEXT: The putative association between proinflammatory and hyperinsulinemic dietary patterns and susceptibility to gestational diabetes mellitus (GDM) remains unclear. OBJECTIVE: We aimed to compare the risk associated with the Mediterranean diet, as well as insulinemic and proinflammatory dietary patterns, in relation to the occurrence of GDM, and evaluate their predictive value. METHODS: We prospectively followed 8, 495 women from the Maternal and Infant Health cohort in Hefei, China (2015-2021). Using a food frequency questionnaire, we calculated the Empirical Dietary Inflammatory Pattern (EDIP), the Empirical Dietary Index for Hyperinsulinemia (EDIH) score, and the Mediterranean diet (MD) score. GDM was diagnosed based on a 2-hour 75-gram oral glucose tolerance test conducted between 24 to 28 weeks of gestation. Logistic regression was used to estimate the risk of GDM, while Receiver Operating Characteristic (ROC) curves were constructed to evaluate the predictive performance of the empirical dietary index for GDM. RESULTS: Participants who followed hyperinsulinemic or proinflammatory dietary patterns to the greatest extent had a higher risk of developing GDM. The OR for the highest quartile compared to the lowest quartile were 1.39 (95% CI: 1.30-1.49) for EDIH and 2.40 (95% CI: 1.88-3.01) for EDIP. The OR for the lowest quartile compared to the highest quartile was 1.33 (95% CI:1.14-1.55)for MD. The ROC curve analysis indicated that the combination of EDIP and EDIH (AUC = 0.81, 95% CI: 0.78-0.82, P = 0.003) can effectively predict the occurrence of GDM. CONCLUSIONS: Utilizing both empirical dietary indexes, EDIP and EDIH, might offer a potentially more effective approach in preventing GDM when compared to solely focusing on adherence to the Mediterranean diet pattern.

Superelastic carbon aerogels with anisotropic and hierarchically-enhanced cellular structure for wearable piezoresistive sensors.

Elastic carbon aerogels have promising applications in the field of wearable sensors. Herein, a new strategy for preparing carbon aerogels with excellent compressive strength and strain, shape recovery, and fatigue resistance was proposed based on the structure design and carbonization optimization of nanocellulose-based precursor aerogels. By the combination of directional freezing and zinc ion cross-linking, bacterial cellulose (BC)/alginate (SA) composite aerogels with high elasticity and compressive strength were first achieved. The existance of zinc ions also significantly improved the carbon retention rate and inhibited structural shrinkage, thus making the carbon aerogels retain ultra-high elasticity and fatigue resistance after compression. Moreover, the carbon aerogel possessed excellent piezoresistive pressure sensing performance with a wide detection range of 0-7.8 kPa, high sensitivity of 11.04 kpa-1, low detection limit (2 % strain), fast response (112 ms), and good durability (over 1,000 cycles). Based on these excellent properties, the carbon aerogel pressure sensors were further successfully used for human motion monitoring, from joint motion to and speech recognition.

Controllable Synthesis of Transferable Ultrathin Bi2Ge(Si)O5 Dielectric Alloys with Composition-Tunable High-κ Properties.

Two-dimensional (2D) alloys hold great promise to serve as important components of 2D transistors, since their properties allow continuous regulation by varying their compositions. However, previous studies are mainly limited to the metallic/semiconducting ones as contact/channel materials, but very few are related to the insulating dielectrics. Here, we use a facile one-step chemical vapor deposition (CVD) method to synthesize ultrathin Bi2SixGe1-xO5 dielectric alloys, whose composition is tunable over the full range of x just by changing the relative ratios of the GeO2/SiO2 precursors. Moreover, their dielectric properties are highly composition-tunable, showing a record-high dielectric constant of >40 among CVD-grown 2D insulators. The vertically grown nature of Bi2GeO5 and Bi2SixGe1-xO5 enables polymer-free transfer and subsequent clean van der Waals integration as the high-κ encapsulation layer to enhance the mobility of 2D semiconductors. Besides, the MoS2 transistors using Bi2SixGe1-xO5 alloy as gate dielectrics exhibit a large Ion/Ioff (>108), ideal subthreshold swing of ∼61 mV/decade, and a small gate hysteresis (∼5 mV). Our work not only gives very few examples on controlled CVD growth of insulating dielectric alloys but also expands the family of 2D single-crystalline high-κ dielectrics.

Pivotal Evaluation of Novel Dedicated Venous Stent for Iliofemoral Venous Obstruction: A Prospective Cohort Study.

PURPOSE: The purpose was to evaluate the clinical outcomes of a dedicated venous stent with the tripartite composite segments for the treatment of iliofemoral venous obstruction (IVO) in a mixed cohort of nonthrombotic iliac vein lesion (NIVL) and post-thrombotic syndrome (PTS) over a period of 12 months. METHODS: The Grency Trial is a prospective, multicenter, single-arm, open-label, pivotal study, which was conducted at 18 large tertiary hospitals in China from August 2019 to October 2020. A total of 133 hospitalized patients were screened and 110 patients with clinical, etiology, anatomical, and pathophysiology clinical class (CEAP) clinical grade C>3 and iliac vein stenosis >50% or occlusion, including 72 patients with NIVL and 38 patients with PTS, were implanted with Grency venous stents. Primary endpoint was stent patency at 12 months follow-up, and secondary outcomes were technical success; improvement in venous clinical severity score (VCSS) at 3, 6, and 12 month follow-up; and rates of clinical adverse events. RESULTS: Among 110 patients who were implanted with Grency venous stents, 107 patients completed the 12 month follow-up. All 129 stents were successfully implanted in 110 limbs. Twelve-month primary patency rate was 94.39% [95% confidence interval [CI]=88.19%-97.91%] overall, and 100% [94.94%-100%] and 83.33% [67.19%-93.63%] in the NIVL and PTS subgroups, respectively. Venous clinical severity score after iliac vein stenting improved significantly up to 12 months follow-up. There were 3 early major adverse events (1 intracerebral hemorrhage and 2 stent thrombosis events related to anticoagulation therapy), and 7 late major adverse events (1 cardiovascular death, 1 intracranial hemorrhage with uncontrolled hypertension, and 5 in-stent restenosis cases without stent fractures or migration). CONCLUSIONS: The Grency venous stent system appeared excellent preliminary safe and effective for IVO treatment. Further large-scale studies with longer-term follow-up are needed to evaluate long-term patency and durability of stent. CLINICAL IMPACT: The design of venous stents for iliofemoral venous obstruction (IVO) must address engineering challenges distinct from those encountered in arterial stenting. The Grency venous stent, a nitinol self-expanding stent specifically tailored for IVO, features a composite structure designed to meet the stent requirements of various iliac vein segments. The Grency Trial is a prospective, multicenter, single-arm, open-label pivotal study aimed at evaluating the efficacy and safety of the Grency stent system. Following a 12-month follow-up period, the Grency venous stent system has demonstrated both safety and efficacy in treating iliofemoral venous outflow obstruction.

Constructing N-Containing Poly(p-Phenylene) (PPP) Films Through A Cathodic-Dehalogenation Polymerization Method.

Developing the films of N-containing unsubstituted poly(p-phenylene) (PPP) films for diverse applications is significant and highly desirable because the replacement of sp2 C atoms with sp2 N atoms will bring novel properties to the as-prepared polymers. In this research, an electrochemical-dehalogenation polymerization strategy is employed to construct two N-containing PPP films under constant potentials, where 2,5-diiodopyridine (DIPy) and 2,5-dibromopyrazine (DBPz) are used as starting agents. The corresponding polymers are named CityU-23 (for polypyridine) and CityU-24 (for polypyrazine). Moreover, it is found that both polymers can form films in situ on different conductive substrates (i.e., silicon, gold, ITO, and nickel), satisfying potential device fabrication. Furthermore, the as-obtained thin films of CityU-23 and CityU-24 exhibit good performance of alkaline hydrogen evolution reaction with the overpotential of 212.8 and 180.7 mV and the Tafel slope of 157.0 and 122.4 mV dec-1, respectively.

The orientation of CpG conjugation on aluminum oxyhydroxide nanoparticles determines the immunostimulatory effects of combination adjuvants.

In subunit vaccines, aluminum salts (Alum) are commonly used as adjuvants, but with limited cellular immune responses. To overcome this limitation, CpG oligodeoxynucleotides (ODNs) have been used in combination with Alum. However, current combined usage of Alum and CpG is limited to linear mixtures, and the underlying interaction mechanism between CpG and Alum is not well understood. Thus, we propose to chemically conjugate Alum nanoparticles and CpG (with 5' or 3' end exposed) to design combination adjuvants. Our study demonstrates that compared to the 3'-end exposure, the 5'-end exposure of CpG in combination adjuvants (Al-CpG-5') enhances the activation of bone-marrow derived dendritic cells (BMDCs) and promotes Th1 and Th2 cytokine secretion. We used the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen (HBsAg) as model antigens to demonstrate that Al-CpG-5' enhanced antigen-specific antibody production and upregulated cytotoxic T lymphocyte markers. Additionally, Al-CpG-5' allows for coordinated adaptive immune responses even at lower doses of both CpG ODNs and HBsAg antigens, and enhances lymph node transport of antigens and activation of dendritic cells, promoting Tfh cell differentiation and B cell activation. Our novel Alum-CPG strategy points the way towards broadening the use of nanoadjuvants for both prophylactic and therapeutic vaccines.

Cellular senescence and metabolic reprogramming model based on bulk/single-cell RNA sequencing reveals PTGER4 as a therapeutic target for ccRCC.

Clear cell renal cell carcinoma (ccRCC) is the prevailing histological subtype of renal cell carcinoma and has unique metabolic reprogramming during its occurrence and development. Cell senescence is one of the newly identified tumor characteristics. However, there is a dearth of methodical and all-encompassing investigations regarding the correlation between the broad-ranging alterations in metabolic processes associated with aging and ccRCC. We utilized a range of analytical methodologies, such as protein‒protein interaction network analysis and least absolute shrinkage and selection operator (LASSO) regression analysis, to form and validate a risk score model known as the senescence-metabolism-related risk model (SeMRM). Our study demonstrated that SeMRM could more precisely predict the OS of ccRCC patients than the clinical prognostic markers in use. By utilizing two distinct datasets of ccRCC, ICGC-KIRC (the International Cancer Genome Consortium) and GSE29609, as well as a single-cell dataset (GSE156632) and real patient clinical information, and further confirmed the relationship between the senescence-metabolism-related risk score (SeMRS) and ccRCC patient progression. It is worth noting that patients who were classified into different subgroups based on the SeMRS exhibited notable variations in metabolic activity, immune microenvironment, immune cell type transformation, mutant landscape, and drug responsiveness. We also demonstrated that PTGER4, a key gene in SeMRM, regulated ccRCC cell proliferation, lipid levels and the cell cycle in vivo and in vitro. Together, the utilization of SeMRM has the potential to function as a dependable clinical characteristic to increase the accuracy of prognostic assessment for patients diagnosed with ccRCC, thereby facilitating the selection of suitable treatment strategies.

The bacteriome-coupled phage communities continuously contract and shift to orchestrate the traditional rice vinegar fermentation.

Amounts of microbiome studies have uncovered the microbial communities of traditional food fermentations, while in which the phageome development with time is poorly understood. Here, we conducted a study to decipher both phageome and bacteriome of the traditional rice vinegar fermentation. The vinegar phageomes showed significant differences in the alpha diversity, network density and clustering coefficient over time. Peduoviridae had the highest relative abundance. Moreover, the phageome negatively correlated to the cognate bacteriome in alpha diversity, and undergone constantly contracting and shifting across the temporal scale. Nevertheless, 257 core virial clusters (VCs) persistently occurred with time whatever the significant impacts imposed by the varied physiochemical properties. Glycoside hydrolase (GH) and glycosyltransferase (GT) families genes displayed the higher abundances across all samples. Intriguingly, diversely structuring of toxin-antitoxin systems (TAs) and CRISPR-Cas arrays were frequently harbored by phage genomes. Their divergent organization and encoding attributes underlie the multiple biological roles in modulation of network and/or contest of phage community as well as bacterial host community. This phageome-wide mapping will fuel the current insights of phage community ecology in other traditional fermented ecosystems that are challenging to decipher.

ECL cytosensor for sensitive and label-free detection of circulating tumor cells based on hierarchical flower-like gold microstructures.

The development of sensitive and efficient cell sensing strategies to detect circulating tumor cells (CTCs) in peripheral blood is crucial for the early diagnosis and prognostic assessment of cancer clinical treatment. Herein, an array of hierarchical flower-like gold microstructures (HFGMs) with anisotropic nanotips was synthesized by a simple electrodeposition method and used as a capture substrate to construct an ECL cytosensor based on the specific recognition of target cells by aptamers. The complex topography of the HFGMs array not only catalyzed the enhancement of ECL signals, but also induced the cells to generate more filopodia, improving the capture efficiency and shortening the capture time. The effect of topographic roughness on cell growth and adhesion propensity was also investigated, while the cell capture efficiency was proposed to be an important indicator affecting the accuracy of the ECL cytosensor. In addition, the capture of cells on the electrode surface increased the steric hindrance, which caused ECL signal changes in the Ru(bpy)32+ and TPrA system, realizing the quantitative detection of MCF-7 cells. The detection range of the sensor was from 102 to 106 cells mL-1 and the detection limit was 18 cells mL-1. The proposed detection method avoids the process of separation, labeling and counting, which has great potential for sensitive detection in clinical applications.

Slimmable transformer with hybrid axial-attention for medical image segmentation.

The transformer architecture has achieved remarkable success in medical image analysis owing to its powerful capability for capturing long-range dependencies. However, due to the lack of intrinsic inductive bias in modeling visual structural information, the transformer generally requires a large-scale pre-training schedule, limiting the clinical applications over expensive small-scale medical data. To this end, we propose a slimmable transformer to explore intrinsic inductive bias via position information for medical image segmentation. Specifically, we empirically investigate how different position encoding strategies affect the prediction quality of the region of interest (ROI) and observe that ROIs are sensitive to different position encoding strategies. Motivated by this, we present a novel Hybrid Axial-Attention (HAA) that can be equipped with pixel-level spatial structure and relative position information as inductive bias. Moreover, we introduce a gating mechanism to achieve efficient feature selection and further improve the representation quality over small-scale datasets. Experiments on LGG and COVID-19 datasets prove the superiority of our method over the baseline and previous works. Internal workflow visualization with interpretability is conducted to validate our success better; the proposed slimmable transformer has the potential to be further developed into a visual software tool for improving computer-aided lesion diagnosis and treatment planning.

[Reflections on good manufacturing practice and quality control system of personalized traditional Chinese medicine preparations].

Personalized traditional Chinese medicine(TCM) preparations have entered a stage of rapid development. The key to the healthy development of this industry is to establish a sound manufacturing standard and quality control system. This paper analyzed the characteristics of personalized TCM preparations and drew reference from the quality management standards in the production of commissioned decoctions and oral pastes, on the basis of which the production quality management scheme and cautions for the safe production of personalized TCM preparations was put forward with consideration to various problems that may exist and occur in the production of such preparations. It provided references for formulating the production standards and quality management system of personalized TCM preparations. The production standards and quality control system should develop with the times. In the future, modern technologies such as big data and artificial intelligence should be employed to achieve the automated and intelligent production and establish a sound quality traceability system, online control strategy, and safety management mode of personalized TCM preparations, which will ensure the healthy development of this industry under requirement of good manufacturing practice(GMP).

DNA liquid crystals with AIE effect toward humidity-indicating biomaterials.

In this study, by fabricating DNA doped with tetraphenylethene-containing ammonium surfactant, the resulting solvent-free DNA ionic complex could undergo a humidity-induced phase change that could be well tracked by the fluorescence signal of the surfactant. Taking advantage of the humidity-induced change in fluorescence, the reported ionic DNA complex could accurately indicate the humidity in real time.