Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C at Human Kinetochores.

Kinetochores, multisubunit protein assemblies, connect chromosomes to spindle microtubules to promote chromosome segregation. The 10-subunit KMN assembly (comprising KNL1, MIS12, and NDC80 complexes, designated KNL1C, MIS12C, and NDC80C) binds microtubules and regulates mitotic checkpoint function through NDC80C and KNL1C, respectively. MIS12C, on the other hand, connects the KMN to the chromosome-proximal domain of the kinetochore through a direct interaction with CENP-C. The structural basis for this crucial bridging function of MIS12C is unknown. Here, we report crystal structures of human MIS12C associated with a fragment of CENP-C and unveil the role of Aurora B kinase in the regulation of this interaction. The structure of MIS12:CENP-C complements previously determined high-resolution structures of functional regions of NDC80C and KNL1C and allows us to build a near-complete structural model of the KMN assembly. Our work illuminates the structural organization of essential chromosome segregation machinery that is conserved in most eukaryotes.

Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes.

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

Leveraging SEER data through machine learning to predict distant lymph node metastasis and prognosticate outcomes in hepatocellular carcinoma patients.

OBJECTIVES: This study aims to develop and validate machine learning-based diagnostic and prognostic models to predict the risk of distant lymph node metastases (DLNM) in patients with hepatocellular carcinoma (HCC) and to evaluate the prognosis for this cohort. DESIGN: Utilizing a retrospective design, this investigation leverages data extracted from the Surveillance, Epidemiology, and End Results (SEER) database, specifically the January 2024 subset, to conduct the analysis. PARTICIPANTS: The study cohort consists of 15,775 patients diagnosed with HCC as identified within the SEER database, spanning 2016 to 2020. METHOD: In the construction of the diagnostic model, recursive feature elimination (RFE) is employed for variable selection, incorporating five critical predictors: age, tumor size, radiation therapy, T-stage, and serum alpha-fetoprotein (AFP) levels. These variables are the foundation for a stacking ensemble model, which is further elucidated through Shapley Additive Explanations (SHAP). Conversely, the prognostic model is crafted utilizing stepwise backward regression to select pertinent variables, including chemotherapy, radiation therapy, tumor size, and age. This model culminates in the development of a prognostic nomogram, underpinned by the Cox proportional hazards model. MAIN OUTCOME MEASURES: The outcome of the diagnostic model is the occurrence of DLNM in patients. The outcome of the prognosis model is determined by survival time and survival status. RESULTS: The integrated model developed based on stacking demonstrates good predictive performance and high interpretative variability and differentiation. The area under the curve (AUC) in the training set is 0.767, while the AUC in the validation set is 0.768. The nomogram, constructed using the Cox model, also demonstrates consistent and strong predictive capabilities. At the same time, we recognized elements that have a substantial impact on DLNM and the prognosis and extensively discussed their significance in the model and clinical practice. CONCLUSION: Our study identified key predictive factors for DLNM and elucidated significant prognostic indicators for HCC patients with DLNM. These findings provide clinicians with valuable tools to accurately identify high-risk individuals for DLNM and conduct more precise risk stratification for this patient subgroup, potentially improving management strategies and patient outcomes.

A 3,3'-Difluoro-2,2'-Bithiophene Based Donor Polymer Realizing High Efficiency (>17%) Single Junction Binary Organic Solar Cells.

In this study, two novel donor-acceptor (D-A) copolymers are designed and synthesized, DTBT-2T and DTBT-2T2F with 2,2'-bithiophene or 3,3'-difluoro-2,2'-bithiophene as the donor unit and dithienobenzothiadiazole as the acceptor unit, and used them as donor materials in non-fullerene organic solar cells (OSCs). Due to enhanced planarity of polymer chains resulted by the intramolecular F···S noncovalent interactions, the incorporation of 3,3'-difluoro-2,2'-bithiophene unit instead of 2,2'-bithiophene into the polymers can enhance their molecular packing, crystallinity and hole mobility. The DTBT-2T:L8-BO based binary OSCs deliver a power conversion efficiency (PCE) of only 9.71% with a Voc of 0.78 V, a Jsc of 20.69 mA cm-2 , and an FF of 59.67%. Moreover, the introduction of fluoro atoms can lower the highest occupied molecular orbital levels. As a result, DTBT-2T2F:L8-BO based single-junction binary OSCs exhibited less recombination loss, more balanced charge mobility, and more favorable morphology, resulting in an impressive PCE of 17.03% with a higher Voc of 0.89 V, a Jsc of 25.40 mA cm-2, and an FF of 75.74%. These results indicate that 3,3'-difluoro-2,2'-bithiophene unit can be used as an effective building block to synthesize high performance polymer donor materials. This work greatly expands the selection range of donor units for constructing high-performance polymers.

Organic Electrolyte Additive: Dual Functions Toward Fast Sulfur Conversion and Stable Li Deposition for Advanced Li-S Batteries.

Lithium-sulfur (Li-S) battery is of great potential for the next generation energy storage device due to the high specific capacity energy density. However, the sluggish kinetics of S redox and the dendrite Li growth are the main challenges to hinder its commercial application. Herein, an organic electrolyte additive, i.e., benzyl chloride (BzCl), is applied as the remedy to address the two issues. In detail, BzCl can split into Bz· radical to react with the polysulfides, forming a Bz-S-Bz intermediate, which changes the conversion path of S and improves the kinetics by accelerating the S splitting. Meanwhile, a tight and robust solid electrolyte interphase (SEI) rich in inorganic ingredients namely LiCl, LiF, and Li2O, is formed on the surface of Li metal, accelerating the ion conductivity and blocking the decomposition of the solvent and lithium polysulfides. Therefore, the Li-S battery with BzCl as the additive remains high capacity of 693.2 mAh g-1 after 220 cycles at 0.5 C with a low decay rate of 0.11%. This work provides a novel strategy to boost the electrochemical performances in both cathode and anode and gives a guide on the electrolyte design toward high-performance Li-S batteries.

Coordinated activation of DNMT3a and TET2 in cancer stem cell-like cells initiates and sustains drug resistance in hepatocellular carcinoma.

BACKGROUND: Resistance to targeted therapies represents a significant hurdle to successfully treating hepatocellular carcinoma (HCC). While epigenetic abnormalities are critical determinants of HCC relapse and therapeutic resistance, the underlying mechanisms are poorly understood. We aimed to address whether and how dysregulated epigenetic regulators have regulatory and functional communications in establishing and maintaining drug resistance. METHODS: HCC-resistant cells were characterized by CCK-8, IncuCyte Live-Cell analysis, flow cytometry and wound-healing assays. Target expression was assessed by qPCR and Western blotting. Global and promoter DNA methylation was measured by dotblotting, methylated-DNA immunoprecipitation and enzymatic digestion. Protein interaction and promoter binding of DNMT3a-TET2 were investigated by co-immunoprecipitation, ChIP-qPCR. The regulatory and functional roles of DNMT3a and TET2 were studied by lentivirus infection and puromycin selection. The association of DNMT and TET expression with drug response and survival of HCC patients was assessed by public datasets, spearman correlation coefficients and online tools. RESULTS: We identified the coordination of DNMT3a and TET2 as an actionable mechanism of drug resistance in HCC. The faster growth and migration of resistant HCC cells were attributed to DNMT3a and TET2 upregulation followed by increased 5mC and 5hmC production. HCC patients with higher DNMT3a and TET2 had a shorter survival time with a less favorable response to sorafenib therapy than those with lower expression. Cancer stem cell-like cells (CSCs) displayed DNMT3a and TET2 overexpression, which were insensitive to sorafenib. Either genetic or pharmacological suppression of DNMT3a or/and TET2 impaired resistant cell growth and oncosphere formation, and restored sorafenib sensitivity. Mechanistically, DNMT3a did not establish a regulatory circuit with TET2, but formed a complex with TET2 and HDAC2. This complex bound the promoters of oncogenes (i.e., CDK1, CCNA2, RASEF), and upregulated them without involving promoter DNA methylation. In contrast, DNMT3a-TET2 crosstalk silences tumor suppressors (i.e., P15, SOCS2) through a corepressor complex with HDAC2 along with increased promoter DNA methylation. CONCLUSIONS: We demonstrate that DNMT3a and TET2 act coordinately to regulate HCC cell fate in DNA methylation-dependent and -independent manners, representing strong predictors for drug resistance and poor prognosis, and thus are promising therapeutic targets for refractory HCC.

AnWRKY29 and AnHSP90 synergistically modulate trehalose levels in a desert shrub leaves during osmotic stress.

Trehalose, a biological macromolecule with osmotic adjustment properties, plays a crucial role during osmotic stress. As a psammophyte, Ammopiptanthus nanus relies on the accumulation of organic solutes to respond to osmotic stress. We utilized virus-induced gene silencing technology for the first time in the desert shrub A. nanus to confirm the central regulatory role of AnWRKY29 in osmotic stress, as it controls the transcription of AnTPS11 (trehalose-6-phosphate synthase 11). Further investigation has shown that AnHSP90 may interact with AnWRKY29. The AnHSP90 gene is sensitive to osmotic stress, underscoring its pivotal role in orchestrating the response to such adverse conditions. By directly targeting the W-box element within the AnTPS11 promoter, AnWRKY29 effectively enhances the transcriptional activity of AnTPS11, which is facilitated by AnHSP90. This discovery highlights the critical role of AnWRKY29 and AnHSP90 in enabling organisms to adapt to and cope effectively with osmotic stress, which can be a crucial factor in A. nanus survival and overall ecological resilience. Collectively, uncovering the molecular mechanisms underlying the osmotic responses of A. nanus is paramount for comprehending and augmenting the osmotic tolerance mechanisms of psammophyte shrub plants.

Connectivity Network Feature Sharing in Single-Cell RNA Sequencing Data Identifies Rare Cells.

Single-cell RNA sequencing is a valuable technique for identifying diverse cell subtypes. A key challenge in this process is that the detection of rare cells is often missed by conventional methods due to low abundance and subtle features of these cells. To overcome this, we developed SCLCNF (Local Connectivity Network Feature Sharing in Single-Cell RNA sequencing), a novel approach that identifies rare cells by analyzing features uniquely expressed in these cells. SCLCNF creates a cellular connectivity network, considering how each cell relates to its neighbors. This network helps to pinpoint coexpression patterns unique to rare cells, utilizing a rarity score to confirm their presence. Our method performs better in detecting rare cells than existing techniques, offering enhanced robustness. It has proven to be effective in human gastrula data sets for accurately pinpointing rare cells, and in sepsis data sets where it uncovers previously unidentified rare cell populations.

Screening and Evaluation of Children's Sensitively Toxic Chemicals in New Mosquito Repellent Products Based on a Nationwide Investigation.

New mosquito repellent products (NMRPs) are emerging popular repellents among children. There are increasing reports on children's sensitization reactions caused by NMRPs, while regulations on their productions, sales, or usage are still lacking. One of the reasons could be the missing comprehensive risk assessment. We first conducted a nationwide investigation on children's NMRP usage preferences. Then, we high-throughput screened volatile or semivolatile organic chemicals (VOCs/SVOCs) in five representative NMRPs by the headspace gas chromatography-orbitrap high-resolution mass spectrometry analytical method. After that, toxic compounds were recognized based on the toxicity forecaster (ToxCast) database. A total of 277 VOCs/SVOCs were recognized, and 70 of them were identified as toxic compounds. In a combination of concentrations, toxicities, absorption, distribution, metabolism, and excretion characteristics in the body, 28 chemicals were finally proposed as priority-controlled compounds in NMRPs. Exposure risks of recognized toxic chemicals through NMRPs by inhalation and dermal intake for children across the country were also assessed. Average daily intakes were in the range of 0.20-7.31 mg/kg/day for children in different provinces, and the children in southeastern coastal provinces were found to face higher exposure risks. By controlling the high-priority chemicals, the risks were expected to be reduced by about 46.8% on average. Results of this study are therefore believed to evaluate exposure risks, encourage safe production, and promote reasonable management of NMRPs.

Priority Organic Pollutant Monitoring Inventory and Relative Risk Reduction Potential for Solid Waste Incineration.

Incineration is a promising sustainable treatment method for solid waste. However, the ongoing revelation of new toxic pollutants in this process has become a controversial issue impeding its development. Thus, identifying and regulating high-risk pollutants emerge as pivotal strides toward reconciling this debate. In this study, we proposed a workflow aimed at establishing priority monitoring inventories for organic compounds emitted by industries involving full-component structural recognition, environmental behavior prediction, and emission risk assessment, specifically focusing on solid waste incineration (SWI). A total of 174 stack gas samples from 29 incinerators were first collected. Nontarget full organic recognition technology was then deployed to analyze these samples, and 646 organic compounds were identified. The characteristics, i.e., toxicity effects, toxicity concentrations, persistence, and bioaccumulation potential, of these compounds were assessed and ranked based on the TOXCAST database from the US Environmental Protection Agency and structural effect models. Combined with consideration of changes in seasons and waste types, a priority control inventory consisting of 28 organic pollutants was finally proposed. The risks associated with SWI across different regions in China and various countries were assessed, and results pinpointed that by controlling the priority pollutants, the average global emission risk attributed to SWI was anticipated to be reduced by 71.4%. These findings offer significant guidance for decision-making in industrial pollutant management, emphasizing the importance of targeted regulation and monitoring to enhance the sustainability and safety of incineration processes.

Development of a certified reference material for D-phenylalanine with evaluation of enantiomeric purity.

D-Phenylalanine (D-Phe) is a small chiral organic molecule that is both an important pharmaceutical intermediate and used as a calibrator for quantifying amino acids in liquid chromatography-circular dichroism. We have developed a process for a national certified reference material (CRM) for D-Phe following ISO 17034:2016. The identity of D-Phe was confirmed using mass spectrometry (MS) and nuclear magnetic resonance (NMR), infrared, and ultraviolet (UV) spectroscopy. The absolute optical conformation was also determined using circular dichroism (CD) spectroscopy and optical rotation measurements. Impurities were identified via liquid chromatography (LC) with a UV-Vis detector and a charged aerosol detector (CAD) and LC-MS. Both mass balance and quantitative NMR were employed for value assessment, and the associated uncertainty was evaluated. The certified purity was determined to be 0.995 ± 0.003 g/g, a validation that was confirmed by CD using L-Phe CRM as a calibrator. Twenty milligrams of raw material was packed in sealed brown glass tubes for storage, and no inhomogeneity was observed. Stability tests revealed that the D-Phe CRM remained stable at -20 °C for at least 26 months, at 4 °C for at least 14 days, and at 25 °C and 60 °C for at least 7 days. The D-Phe CRM can be used to ensure the accuracy and reliability of D-Phe quantitation in the pharmaceutical field and also as a calibrator to ensure traceability to the International System of Units (SI) for L-Phe quantitation and protein purity analysis using LC-CD methods. The approach outlined in this paper also has potential for use in the development of other chiral CRMs.

Reliable biological and multi-omics research through biometrology.

Metrology is the science of measurement and its applications, whereas biometrology is the science of biological measurement and its applications. Biometrology aims to achieve accuracy and consistency of biological measurements by focusing on the development of metrological traceability, biological reference measurement procedures, and reference materials. Irreproducibility of biological and multi-omics research results from different laboratories, platforms, and analysis methods is hampering the translation of research into clinical uses and can often be attributed to the lack of biologists' attention to the general principles of metrology. In this paper, the progresses of biometrology including metrology on nucleic acid, protein, and cell measurements and its impacts on the improvement of reliability and comparability in biological research are reviewed. Challenges in obtaining more reliable biological and multi-omics measurements due to the lack of primary reference measurement procedures and new standards for biological reference materials faced by biometrology are discussed. In the future, in addition to establishing reliable reference measurement procedures, developing reference materials from single or multiple parameters to multi-omics scale should be emphasized. Thinking in way of biometrology is warranted for facilitating the translation of high-throughput omics research into clinical practices.

Identification of multiple odorant receptors essential for pyrethrum repellency in Drosophila melanogaster.

Pyrethrum extract from dry flowers of Tanacetum cinerariifolium (formally Chrysanthemum cinerariifolium) has been used globally as a popular insect repellent against arthropod pests for thousands of years. However, the mechanistic basis of pyrethrum repellency remains unknown. In this study, we found that pyrethrum spatially repels and activates olfactory responses in Drosophila melanogaster, a genetically tractable model insect, and the closely-related D. suzukii which is a serious invasive fruit crop pest. The discovery of spatial pyrethrum repellency and olfactory response to pyrethrum in D. melanogaster facilitated our identification of four odorant receptors, Or7a, Or42b, Or59b and Or98a that are responsive to pyrethrum. Further analysis showed that the first three Ors are activated by pyrethrins, the major insecticidal components in pyrethrum, whereas Or98a is activated by (E)-ß-farnesene (EBF), a sesquiterpene and a minor component in pyrethrum. Importantly, knockout of Or7a, Or59b or Or98a individually abolished fly avoidance to pyrethrum, while knockout of Or42b had no effect, demonstrating that simultaneous activation of Or7a, Or59b and Or98a is required for pyrethrum repellency in D. melanogaster. Our study provides insights into the molecular basis of repellency of one of the most ancient and globally used insect repellents. Identification of pyrethrum-responsive Ors opens the door to develop new synthetic insect repellent mixtures that are highly effective and broad-spectrum.

Experiences of family caregivers of patients with end-of-life cancer during the transition from hospital to home palliative care: a qualitative study.

BACKGROUND: The transition of family caregivers of patients with end-of-Life cancer receiving palliative care from hospital to home is a complex and challenging process. This phase of care involves not only the physical and psychological health of the patient but also the role adaptation and emotional support of the family caregivers. To gain a deeper understanding of the various experiences and feelings during this process, we conducted a qualitative study. METHODS: This study employed a descriptive phenomenological research method. The interviews focused on the specific experiences, challenges faced, support received, and coping strategies of family caregivers of patients with end-of-life cancer during the transition from hospital to home palliative care. All data were treated with strict confidentiality, and recordings and transcriptions were made with the participants' consent. RESULTS: A total of 15 family caregivers participated. Four main themes and nine sub-themes were identified: complex transition process (anxiety about uncertainty, resistance to transition), discontinuity in care (insufficient discharge guidance, lack of continuous communication mechanisms), post-discharge continuous care needs (need for home care knowledge and skills, social and emotional support, grief counselling and death education), and personal growth and gains (enhanced coping ability, increased psychological resilience). CONCLUSION: Family caregivers face numerous emotional, cognitive, practical, and social support challenges during the transition from hospital to home care. To improve the caregiving experience and quality of life, appropriate training and support should be provided to better meet the caregivers' needs.

Evaluating nitrogen dynamic and utilization under controlled-release fertilizer application for sunflowers in an arid region: Experimental and modeling approach.

Traditional nitrogen fertilizers (TNF), such as urea, percolate easily in arid fields, posing low nitrogen use efficiency (NUE) and a high non-point pollution risk. Controlled-release fertilizers (CRF) exhibit significantly lower deep seepage, rendering it a favorable choice in arid fields due to its ability to enhance NUE through slow-release mechanisms. However, current models do not fully account for the soil nitrogen dynamics and crop interactions under controlled-release conditions, and lack quantification. This study improved the APSIM model by adjustment the urea hydrolysis rate to assess the impact of CRF and TNF applications on soil health, crop growth, and water quality. Calibration and validation were conducted through experiments in the Hetao Irrigation District of China from 2019 to 2020, with different nitrogen application rates (135, 225, and 315 kg/ha). The model accurately simulated soil NO3-N concentration (SNC), cumulative NO3-N leaching (CNL), nitrogen uptake (NU), and sunflower yield. During the validation process, R2 and Nash-Sutcliffe efficiency (NSE) values were both above 0.75. Results indicated that the average SNC, NU, and yield under CRF application were significantly higher than those under TNF application, with increases of 38.62%, 44.92%, and 18.38%, respectively. Notably, the proportion of soil nitrogen available (PSNA), a novel metric proposed in this study, was 159.50% higher in the 0-40 cm soil layer with CRF compared to TNF. Additionally, CNL and NO3-N leaching loss rate (NLLR) decreased by 25.76% and 25.77%, respectively. Scenario simulations indicated that the optimal fertilization strategy for this region is to use 180-193.5 kg/ha of CRF with a release period of 80-85.5 d to balance agricultural productivity and ecological protection. This study confirms the significant advantages of CRF in enhancing yield, improving nitrogen management, and promoting environmental sustainability, providing a scientific basis for CRF management strategies and supporting the shift towards more efficient and environmentally friendly agricultural practices.

Designing A-D-A Type Fused-Ring Electron Acceptors with a Bulky 3D Substituent at the Central Donor Core to Minimize Non-Radiative Losses and Enhance Organic Solar Cell Efficiency.

Designing and synthesizing narrow band gap acceptors that exhibit high photoluminescence quantum yield (PLQY) and strong crystallinity is a highly effective, yet challenging, approach to reducing non-radiative energy losses (▵Enr) and boosting the performance of organic solar cells (OSCs). We have successfully designed and synthesized an A-D-A type fused-ring electron acceptor, named DM-F, which features a planar molecular backbone adorned with bulky three-dimensional camphane side groups at its central core. These bulky substituents effectively hinder the formation of H-aggregates of the acceptors, promoting the formation of more J-aggregates and notably elevating the PLQY of the acceptor in the film. As anticipated, DM-F showcases pronounced near-infrared absorption coupled with impressive crystallinity. Organic solar cells (OSCs) leveraging DM-F exhibit a high EQEEL value and remarkably low ▵Enr of 0.14 eV-currently the most minimal reported value for OSCs. Moreover, the power conversion efficiency (PCE) of binary and ternary OSCs utilizing DM-F has reached 16.16 % and 20.09 %, respectively, marking a new apex in reported efficiency within the OSCs field. In conclusion, our study reveals that designing narrow band gap acceptors with high PLQY is an effective way to reduce ▵Enr and improve the PCE of OSCs.

Boosting Organic Solar Cells to Over 18% Efficiency through Dipole-Dipole Interactions in Fluorinated Nonfused Ring Electron Acceptors.

This study successfully designed and synthesized two nonfused ring electron acceptors, 412-6F and 412-6Cl, modified with fluorine and chlorine substituents, respectively. Single-crystal analysis revealed that 412-6F possesses a planar molecular backbone and exhibits pronounced dipole-dipole interactions between the fluorine atoms on the lateral phenyl groups and the carbonyl oxygen atoms on the end groups. This specific interaction promotes dense end-group stacking, leading to a reduced interlayer spacing. Improved crystallinity and coherence length are observed in the D18:412-6F blend film. Conversely, 412-6Cl adopts a more distorted configuration and lacks these interactions. As a result, the organic solar cell (OSC) based on D18:412-6F achieved a remarkable power conversion efficiency of 18.03%, surpassing the performance of the D18:412-6Cl OSC. This underscores the importance of designing novel acceptors with beneficial intermolecular interactions to enhance OSC efficiency, thus providing a new direction for organic photovoltaic advancement.

From clinical variables to multiomics analysis: a margin morphology-based gross classification system for hepatocellular carcinoma stratification.

OBJECTIVE: Selecting interventions for patients with solitary hepatocellular carcinoma (HCC) remains a challenge. Despite gross classification being proposed as a potential prognostic predictor, its widespread use has been restricted due to inadequate studies with sufficient patient numbers and the lack of established mechanisms. We sought to investigate the prognostic impacts on patients with HCC of different gross subtypes and assess their corresponding molecular landscapes. DESIGN: A prospective cohort of 400 patients who underwent hepatic resection for solitary HCC was reviewed and analysed and gross classification was assessed. Multiomics analyses were performed on tumours and non-tumour tissues from 49 patients to investigate the mechanisms underlying gross classification. Inverse probability of treatment weight (IPTW) was used to control for confounding factors. RESULTS: Overall 3-year survival rates varied significantly among the four gross subtypes (type I: 91%, type II: 80%, type III: 74.6%, type IV: 38.8%). Type IV was found to be independently associated with poor prognosis in both the entire cohort and the IPTW cohort. The four gross subtypes exhibited three distinct transcriptional modules. Particularly, type IV tumours exhibited increased angiogenesis and immune score as well as decreased metabolic pathways, together with highest frequency of TP53 mutations. Patients with type IV HCC may benefit from adjuvant intra-arterial therapy other than the other three subtypes. Accordingly, a modified trichotomous margin morphological gross classification was established. CONCLUSION: Different gross types of HCC showed significantly different prognosis and molecular characteristics. Gross classification may aid in development of precise individualised diagnosis and treatment strategies for HCC.

Triglyceride-glucose index as a marker of adverse cardiovascular prognosis in patients with coronary heart disease and hypertension.

BACKGROUND: The triglyceride-glucose (TyG) index has been proposed as a potential predictor of adverse prognosis of cardiovascular diseases (CVDs). However, its prognostic value in patients with coronary heart disease (CHD) and hypertension remains unclear. METHODS: A total of 1467 hospitalized patients with CHD and hypertension from January 2021 to December 2021 were included in this prospective and observational clinical study. The TyG index was calculated as Ln [fasting triglyceride level (mg/dL) × fasting plasma glucose level (mg/dL)/2]. Patients were divided into tertiles according to TyG index values. The primary endpoint was a compound endpoint, defined as the first occurrence of all-cause mortality or total nonfatal CVDs events within one-year follow up. The secondary endpoint was atherosclerotic CVD (ASCVD) events, including non-fatal stroke/transient ischemic attack (TIA) and recurrent CHD events. We used restricted cubic spline analysis and multivariate adjusted Cox proportional hazard models to investigate the associations of the TyG index with primary endpoint events. RESULTS: During the one-year follow-up period, 154 (10.5%) primary endpoint events were recorded, including 129 (8.8%) ASCVD events. After adjusting for confounding variables, for per standard deviation (SD) increase in the TyG index, the risk of incident primary endpoint events increased by 28% [hazard ratio (HR) = 1.28, 95% confidence interval (CI) 1.04-1.59]. Compared with subjects in the lowest tertile (T1), the fully adjusted HR for primary endpoint events was 1.43 (95% CI 0.90-2.26) in the middle (T2) and 1.73 (95% CI 1.06-2.82) in highest tertile (T3) (P for trend = 0.018). Similar results were observed in ASCVD events. Restricted cubic spline analysis also showed that the cumulative risk of primary endpoint events increased as TyG index increased. CONCLUSIONS: The elevated TyG index was a potential marker of adverse prognosis in patients with CHD and hypertension.