Dualities and non-Abelian mechanics.

Dualities are mathematical mappings that reveal links between apparently unrelated systems in virtually every branch of physics1-8. Systems mapped onto themselves by a duality transformation are called self-dual and exhibit remarkable properties, as exemplified by the scale invariance of an Ising magnet at the critical point. Here we show how dualities can enhance the symmetries of a dynamical matrix (or Hamiltonian), enabling the design of metamaterials with emergent properties that escape a standard group theory analysis. As an illustration, we consider twisted kagome lattices9-15, reconfigurable mechanical structures that change shape by means of a collapse mechanism9. We observe that pairs of distinct configurations along the mechanism exhibit the same vibrational spectrum and related elastic moduli. We show that these puzzling properties arise from a duality between pairs of configurations on either side of a mechanical critical point. The critical point corresponds to a self-dual structure with isotropic elasticity even in the absence of spatial symmetries and a twofold-degenerate spectrum over the entire Brillouin zone. The spectral degeneracy originates from a version of Kramers' theorem16,17 in which fermionic time-reversal invariance is replaced by a hidden symmetry emerging at the self-dual point. The normal modes of the self-dual systems exhibit non-Abelian geometric phases18,19 that affect the semiclassical propagation of wavepackets20, leading to non-commuting mechanical responses. Our results hold promise for holonomic computation21 and mechanical spintronics by allowing on-the-fly manipulation of synthetic spins carried by phonons.

On-Site Computed Tomography-Derived Fractional Flow Reserve to Guide Management of Patients With Stable Coronary Artery Disease: The TARGET Randomized Trial.

BACKGROUND: Computed tomography-derived fractional flow reserve (CT-FFR) using on-site machine learning enables identification of both the presence of coronary artery disease and vessel-specific ischemia. However, it is unclear whether on-site CT-FFR improves clinical or economic outcomes when compared with the standard of care in patients with stable coronary artery disease. METHODS: In total, 1216 patients with stable coronary artery disease and an intermediate stenosis of 30% to 90% on coronary computed tomographic angiography were randomized to an on-site CT-FFR care pathway using machine learning or to standard care in 6 Chinese medical centers. The primary end point was the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease who did not undergo intervention within 90 days. Secondary end points included major adverse cardiovascular events, quality of life, symptoms of angina, and medical expenditure at 1 year. RESULTS: Baseline characteristics were similar in both groups, with 72.4% (881/1216) having either typical or atypical anginal symptoms. A total of 421 of 608 patients (69.2%) in the CT-FFR care group and 483 of 608 patients (79.4%) in the standard care group underwent invasive coronary angiography. Compared with standard care, the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease not undergoing intervention was significantly reduced in the CT-FFR care group (28.3% [119/421] versus 46.2% [223/483]; P<0.001). Overall, more patients underwent revascularization in the CT-FFR care group than in the standard care group (49.7% [302/608] versus 42.8% [260/608]; P=0.02), but major adverse cardiovascular events at 1 year did not differ (hazard ratio, 0.88 [95% CI, 0.59-1.30]). Quality of life and symptoms improved similarly during follow-up in both groups, and there was a trend towards lower costs in the CT-FFR care group (difference, -¥4233 [95% CI, -¥8165 to ¥973]; P=0.07). CONCLUSIONS: On-site CT-FFR using machine learning reduced the proportion of patients with stable coronary artery disease undergoing invasive coronary angiography without obstructive disease or requiring intervention within 90 days, but increased revascularization overall without improving symptoms or quality of life, or reducing major adverse cardiovascular events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03901326.

Creation of Interfacial S4-Sn-N2 Electron Pathways for Efficient Light-Driven Hydrogen Evolution.

Establishing effective charge transfer channels between two semiconductors is key to improving photocatalytic activity. However, controlling hetero-structures in situ and designing binding modes pose significant challenges. Herein, hydrolytic SnCl2·2H2O is selected as the metal source and loaded in situ onto a layered carbon nitriden supramolecular precursor. A composite photocatalyst, S4-Sn-N2, with electron pathways of SnS2 and tubular carbon nitriden (TCN) is prepared through pyrolysis and vulcanization processes. The contact interface of SnS2-TCN is increased significantly, promoting the formation of S4-Sn-N2 micro-structure in a Z-scheme charge transfer channel. This structure accelerates the separation and transport of photogenerated carriers, maintains the stronger redox ability, and improves the stability of SnS2 in this series of heterojunctions. Therefore, the catalyst demonstrated exceptional photocatalytic hydrogen production efficiency, achieving a reaction rate of 86.4 µmol h-1, which is 3.15 times greater than that of bare TCN.

Deep learning in the precise assessment of primary Sjögren's Syndrome based on ultrasound images.

OBJECTIVES: This study aimed to investigate the value of a deep learning (DL) model based on greyscale ultrasound (US) images for precise assessment and accurate diagnosis of primary Sjögren's syndrome (pSS). METHODS: This was a multicentre prospective analysis. All pSS patients were diagnosed according to 2016 ACR/EULAR criteria. 72 pSS patients and 72 sex- and age-matched healthy controls recruited between January 2022 and April 2023, together with 41 patients and 41 healthy controls recruited from June 2023 to February 2024 were used for DL model development and validation, respectively. DL model was constructed based on the ResNet 50, input with preprocessed all participants' bilateral submandibular glands (SMGs), parotid glands (PGs), and lacrimal glands (LGs) greyscale US images. Diagnostic performance of the model was compared with two radiologists. The accuracy of prediction and identification performance of DL model were evaluated by calibration curve. RESULTS: 864 and 164 greyscale US images of SMGs, PGs, and LGs were collected for development and validation of the model. The AUCs of DL model in the SMG, PG, and LG were 0.92, 0.93, 0.91 in the model cohort, and were 0.90, 0.88, 0.87 in the validation cohort respectively, outperforming both radiologists. Calibration curves showed the prediction probability of DL model were consistent with the actual probability in both model cohort and validation cohort. CONCLUSION: DL model based on greyscale US images showed diagnostic potential in the precise assessment of pSS patients in the SMG, PG, and LG, outperforming conventional radiologist evaluation.

Prognostic significance of triglyceride-glucose index in acute coronary syndrome patients without standard modifiable cardiovascular risk factors.

BACKGROUND: A significant percentage of patients with acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs) are being identified. Nonetheless, the prognostic influence of the TyG index on adverse events in this type of patient remains unexplored. The aim of this study was to assess the prognostic value of the TyG index among ACS patients without SMuRFs for predicting adverse outcomes. METHODS: This study involved 1140 consecutive patients who were diagnosed with ACS without SMuRFs at Beijing Anzhen Hospital between May 2018 and December 2020 and underwent coronary angiography. Each patient was followed up for a period of 35 to 66 months after discharge. The objective of this study was to examine major adverse cardiac and cerebrovascular events (MACCE), which included all-cause mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, as well as ischemia-driven revascularization. RESULTS: During the median follow-up period of 48.3 months, 220 (19.3%) MACCE events occurred. The average age of the participants was 59.55 ± 10.98 years, and the average TyG index was 8.67 ± 0.53. In the fully adjusted model, when considering the TyG index as either a continuous/categorical variable, significant associations with adverse outcomes were observed. Specifically, for each 1 standard deviation increase in the TyG index within the highest TyG index group, there was a hazard ratio (HR) of 1.245 (95% confidence interval CI 1.030, 1.504) for MACCE and 1.303 (95% CI 1.026, 1.653) for ischemia-driven revascularization (both P < 0.05), when the TyG index was analyzed as a continuous variable. Similarly, when the TyG index was examined as a categorical variable, the HR (95% CI) for MACCE in the highest TyG index group was 1.693 (95% CI 1.051, 2.727) (P < 0.05) in the fully adjusted model, while the HR (95% CI) for ischemia-driven revascularization was 1.855 (95% CI 0.998, 3.449) (P = 0.051). Additionally, the TyG index was found to be associated with a poor prognosis among the subgroup. CONCLUSION: The TyG index is correlated with poor prognosis in patients with ACS without SMuRFs, suggesting that it may be an independent predictive factor of adverse events among these individuals.

Longitudinal assessment of coronary plaque regression related to sodium-glucose cotransporter-2 inhibitor using coronary computed tomography angiography.

BACKGROUND: Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) is a novel oral drug for treating type 2 diabetes mellitus (T2DM) with demonstrated cardiovascular benefits. Previous studies in apolipoprotein E knockout mice have shown that SGLT2i is associated with attenuated progression of atherosclerosis. However, whether this effect extends to T2DM patients with coronary atherosclerosis in real-world settings remains unknown. METHODS: In this longitudinal cohort study using coronary computed tomography angiography (CCTA), T2DM patients who underwent ≥ 2 CCTA examinations at our center between 2019 and 2022 were screened. Eligible patients had multiple study plaques, defined as non-obstructive stenosis at baseline and not intervened during serial CCTAs. Exclusion criteria included a CCTA time interval < 12 months, prior SGLT2i treatment, or initiation/discontinuation of SGLT2i during serial CCTAs. Plaque volume (PV) and percent atheroma volume (PAV) were measured for each study plaque using CCTA plaque analysis software. Patients and plaques were categorized based on SGLT2i therapy and compared using a 1:1 propensity score matching (PSM) analysis. RESULTS: The study included 236 patients (mean age 60.5 ± 9.5 years; 69.1% male) with 435 study plaques (diameter stenosis ≥ 50%, 31.7%). Following SGLT2i treatment for a median duration of 14.6 (interquartile range: 13.0, 20.0) months, overall, non-calcified, and low-attenuation PV and PAV were significantly decreased, while calcified PV and PAV were increased (all p < 0.001). Meanwhile, reductions in overall PV, non-calcified PV, overall PAV, and non-calcified PAV were significantly greater in SGLT2i-treated compared to non-SGLT2i-treated plaques (all p < 0.001). PSM analysis showed that SGLT2i treatment was associated with higher reductions in overall PV (- 11.77 mm3 vs. 4.33 mm3, p = 0.005), non-calcified PV (- 16.96 mm3 vs. - 1.81 mm3, p = 0.017), overall PAV (- 2.83% vs. 3.36%, p < 0.001), and non-calcified PAV (- 4.60% vs. 0.70%, p = 0.003). These findings remained consistent when assessing annual changes in overall and compositional PV and PAV. Multivariate regression models demonstrated that SGLT2i therapy was associated with attenuated progression of overall or non-calcified PV or PAV, even after adjusting for cardiovascular risk factors, medications, and baseline overall or non-calcified PV or PAV, respectively (all p < 0.05). The effect of SGLT2i on attenuating non-calcified plaque progression was consistent across subgroups (all p for interaction > 0.05). CONCLUSIONS: In this longitudinal CCTA cohort of T2DM patients, SGLT2i therapy markedly regressed coronary overall PV and PAV, mainly result from a significant reduction in non-calcified plaque.

Prognostic value of systemic immune-inflammation index in CAD patients: Systematic review and meta-analyses.

BACKGROUND: Systemic immune-inflammation index (SII) is a novel inflammatory marker based on neutrophils, platelets and lymphocytes counts, which has potential prognostic value among coronary artery disease (CAD) patients as described by some observational studies. We aimed to provide higher-certainty evidence to verify the association of SII with poor outcomes of CAD patients. METHODS: PubMed, Web of Science, Embase, Ovid and Scopus were searched to find relevant literature exploring the prognostic value of SII among CAD patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) extracted from the literature included were pooled with the fixed-effect or random-effect model. Sensitivity analyses and subgroup analyses were conducted to detect the source of heterogeneity and evaluate the stability of results. RESULTS: A total of nine studies with 15,832 participants were included. The quantitative synthesis including eight studies with 15,657 participants showed that the high SII was related to the major adverse cardiovascular event in CAD patients (HR with 95% CI: 2.36 [1.67, 3.33]). After eliminating heterogeneity and adjusting for publication bias, the above result was still robust (HR with 95% CI: 1.67 [1.32, 2.12]). Additionally, we also demonstrated the prognostic values of SII for all-cause death, cardiovascular death, myocardial infarction and stroke. CONCLUSION: Higher SII has prognostic values for adverse outcomes in CAD patients.

Switchable hybrid-order optical vortex lattice.

Optical vortex (OV) modulation is a powerful technique for enhancing the intrinsic degrees-of-freedom in structured light applications. Particularly, the lattices involving multiple OVs have garnered significant academic interest owing to their wide applicability in optical tweezers and condensed matter physics. However, all OVs in a lattice possess the same order, which cannot be modulated individually, limiting its versatile application. Herein, we propose, to our knowledge, a novel concept, called the hot-swap method, to design a switchable hybrid-order OV lattice, in which each OV is easily replaced by arbitrary orders. We experimentally generated the switchable hybrid-order OV lattice and studied its characteristics, including interferograms, retrieved phase, energy flow, and orbital angular momentum. Furthermore, the significant advantages of the switchable hybrid-order OV lattice are demonstrated through the independent manipulation of multiple yeast cells. This study provides a novel scheme for accurate control and modulation of OV lattices, which greatly facilitates the diverse applications of optical manipulation and particle trapping and control.

Development of a prediction model for predicting the prevalence of nonalcoholic fatty liver disease in Chinese nurses: the first-year follow data of a web-based ambispective cohort study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is gradually becoming a huge threat to public health. With complex working characteristics, female nurses had been found with high risk of NAFLD. To develop and validate a prediction model to predict the prevalence of NAFLD based on demographic characteristics, work situation, daily lifestyle and laboratory tests in female nurses. METHODS: This study was a part of the Chinese Nurse Cohort Study (The National Nurse Health Study, NNHS), and data were extracted from the first-year follow data collected from 1st June to 1st September 2021 by questionnaires and physical examination records in a comprehensive tertiary hospital. The questionnaires included demographic characteristics, work situation and daily lifestyle. Logistic regression and a nomogram were used to develop and validate the prediction model. RESULTS: A total of 824 female nurses were included in this study. Living situation, smoking history, monthly night shift, daily sleep time, ALT/AST, FBG, TG, HDL-C, UA, BMI, TBil and Ca were independent risk factors for NAFLD occurance. A prediction model for predicting the prevalence of NAFLD among female nurses was developed and verified in this study. CONCLUSION: Living situation, smoking history, monthly night shift, daily sleep time, ALT/AST, FBG, TG, UA, BMI and Ca were independent predictors, while HDL-C and Tbil were independent protective indicators of NAFLD occurance. The prediction model and nomogram could be applied to predict the prevalence of NAFLD among female nurses, which could be used in health improvement. TRIAL REGISTRATION: This study was a part of the Chinese Nurse Cohort Study (The National Nurse Health Study, NNHS), which was a ambispective cohort study contained past data and registered at Clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04572347 ) and the China Cohort Consortium ( http://chinacohort.bjmu.edu.cn/project/102/ ).

Association between the atherogenic index of plasma and coronary collateral circulation in patients with chronic total occlusion.

BACKGROUND: The atherogenic index of plasma (AIP) is considered an independent risk factor for coronary artery disease (CAD). The present study investigated whether AIP correlates with the formation of coronary collateral circulation (CCC) in CAD patients with chronic total occlusion (CTO). METHODS: This retrospective study included 1093 CAD patients with CTO confirmed by coronary angiography from January 2020 to December 2020 at Beijing Anzhen Hospital. Based on the Rentrop scoring system, the patients were divided into the good CCC group and the poor CCC group. AIP was calculated by log (triglyceride/high-density lipoprotein cholesterol). Meanwhile, the study population was further divided into four groups according to the quartiles of AIP. RESULTS: Patients in the poor CCC group exhibited significantly higher AIP compared to those in the good CCC group (0.31 ± 0.27 vs. 0.14 ± 0.24, p < 0.001). Multivariate logistic regression analysis revealed an independent association between AIP and poor CCC, regardless of whether AIP was treated as a continuous or categorical variable (p < 0.001), after adjusting for confounding factors. Besides, this association remained consistent across most subgroups. The incorporation of AIP into the baseline model significantly enhanced the accuracy of identifying poor CCC [area under the curve (AUC): baseline model, 0.661 vs. baseline model + AIP, 0.721, p for comparison < 0.001]. CONCLUSIONS: Elevated AIP is independently associated with an increased risk of poor CCC in CAD patients with CTO, and AIP may improve the ability to identify poor CCC in clinical practice.

Pentapeptide PYRAE triggers ER stress-mediated apoptosis of breast cancer cells in mice by targeting RHBDF1-BiP interaction.

Reinforced cellular responses to endoplasmic reticulum (ER) stress are caused by a variety of pathological conditions including cancers. Human rhomboid family-1 protein (RHBDF1), a multiple transmembrane protein located mainly on the ER, has been shown to promote cancer development, while the binding immunoglobulin protein (BiP) is a key regulator of cellular unfolded protein response (UPR) for the maintenance of ER protein homeostasis. In this study, we investigated the role of RHBDF1 in maintaining ER protein homeostasis in breast cancer cells. We showed that deleting or silencing RHBDF1 in breast cancer cell lines MCF-7 and MDA-MB-231 caused marked aggregation of unfolded proteins in proximity to the ER. We demonstrated that RHBDF1 directly interacted with BiP, and this interaction had a stabilizing effect on the BiP protein. Based on the primary structural motifs of RHBDF1 involved in BiP binding, we found a pentapeptide (PE5) targeted BiP and inhibited BiP ATPase activity. SPR assay revealed a binding affinity of PE5 toward BiP (Kd = 57.7 µM). PE5 (50, 100, 200 µM) dose-dependently promoted ER protein aggregation and ER stress-mediated cell apoptosis in MCF-7 and MDA-MB-231 cells. In mouse 4T1 breast cancer xenograft model, injection of PE5 (10 mg/kg, s.c., every 2 days for 2 weeks) significantly inhibited the tumor growth with markedly increased ER stress and apoptosis-related proteins in tumor tissues. Our results suggest that the ability of RHBDF1 to maintain BiP protein stability is critical to ER protein homeostasis in breast cancer cells, and that the pentapeptide PE5 may serve as a scaffold for the development of a new class of anti-BiP inhibitors.

Mutation breeding of high-stress resistant strains for succinic acid production from corn straw.

The production of succinic acid from corn stover is a promising and sustainable route; however, during the pretreatment stage, byproducts such as organic acids, furan-based compounds, and phenolic compounds generated from corn stover inhibit the microbial fermentation process. Selecting strains that are resistant to stress and utilizing nondetoxified corn stover hydrolysate as a feedstock for succinic acid production could be effective. In this study, A. succinogenes CICC11014 was selected as the original strain, and the stress-resistant strain A. succinogenes M4 was obtained by atmospheric and room temperature plasma (ARTP) mutagenesis and further screening. Compared to the original strain, A. succinogenes M4 exhibited a twofold increase in stress resistance and a 113% increase in succinic acid production when hydrolysate was used as the substrate. By conducting whole-genome resequencing of A. succinogenes M4 and comparing it with the original strain, four nonsynonymous gene mutations and two upstream regions with base losses were identified. KEY POINTS: • A high-stress-resistant strain A. succinogenes M4 was obtained by ARTP mutation •  The production of succinic acid increased by 113% • The mutated genes of A. succinogenes M4 were detected and analyzed.

The clinical role of combined circulating complement C1q and AIP for CAD with LDL-C level below 1.8mmol/L.

BACKGROUND: In the past few years, circulating complement C1q involvement in atherosclerosis has garnered growing research interest in addition to the emerging recognition of the novel lipid marker named atherogenic index of plasma (AIP). Nevertheless, among patients experiencing low-density lipoprotein cholesterol (LDL-C) levels less than 1.8mmol/L, the interplay between C1q combined with the AIP for coronary artery disease (CAD) is ambiguous. METHODS: Patients were stratified into a non-CAD and CAD group according to their coronary angiography. The association between C1q in conjunction with the AIP and CAD was explored using restricted cubic spline analyses and logistic regression models. To assess how it predicted, a receiver operating characteristic analysis was undertaken. RESULTS: A total of 7270 patients comprised 1476 non-CAD patients and 5794 patients diagnosed with CAD were analyzed. A comparison of the two groups showed that the C1q levels were notably higher compared to the CAD group, while AIP exhibited an inverse trend. Across quartiles of C1q, the AIP demonstrated a decline with increasing C1q levels, and significant differences were observed between the groups. A correlation analysis underscored a notable negative correlation between the two variables. Univariate and multivariate logistic regression analyses revealed significant associations between CAD and the C1q quartile groups/AIP. Furthermore, compared with the Q4 group, a decrease in the C1q levels corresponded to an escalation in CAD risk, with the odds ratio rising from 1.661 to 2.314. CONCLUSIONS: In conclusion, there appears to be a notable positive correlation between the combination of C1q with the AIP and CAD.

Correlation Between the Severity of Coronary Artery Disease and Retinal Artery Disease and the Therapeutic Effect of Captopril.

Objective: Investigate the Correlation Between the Severity of Coronary Artery Disease and Retinal Artery Disease, and assess the Efficacy of Angiotensin-Converting Enzyme Inhibitors (ACEIs) Application. Methods: One hundred patients diagnosed with primary hypertension at our hospital were chosen for the study. All patients underwent dual-source 64-layer spiral CT coronary angiography and fundus photography examination. Based on the extent of coronary artery stenosis, the patients were divided into Group A, Group B, Group C, and Group D. Results: In comparison with patients in Group A, individuals in Groups B, C, and D exhibited a notable increase in the severity of retinal artery stenosis and arteriovenous crossing signs (P < .05). Furthermore, the severity of retinal artery stenosis and arteriovenous crossing signs demonstrated an incremental trend with the severity of coronary artery stenosis (P < .05). The arteriovenous crossing sign exhibited a sensitivity of 47.87%, the specificity of 89.21%, positive predictive value of 89.76%, and the negative predictive value of 46.53% for predicting coronary artery stenosis. After treatment, the blood pressure levels of the patients, both systolic (SBP) and diastolic blood pressure (DBP) levels significantly decreased compared to before treatment. Conclusion: A significant positive correlation was observed between the severity of coronary artery lesions and retinal artery lesions. Assessing alterations in retinal blood vessels in hypertensive patients can effectively indicate the extent of coronary artery stenosis indirectly. Concerning medication, the antihypertensive drug captopril demonstrated the potential to alleviate the severity of coronary artery and retinal artery lesions in hypertensive patients. However, specific treatment methods should be tailored to individual patient circumstances.

Pseudohalogen Resurfaced CsPbBr3 Nanocrystals for Bright, Efficient, and Stable Green-Light-Emitting Diodes.

Lead halide perovskite nanocrystals (LHP NCs) are regarded as promising emitters for next-generation ultrahigh-definition displays due to their high color purity and wide color gamut. Recently, the external quantum efficiency (EQE) of LHP NC based light-emitting diodes (PNC LEDs) has been rapidly improved to a level required by practical applications. However, the poor operational stability of the device, caused by halide ion migration at the grain boundary of LHP NC thin films, remains a great challenge. Herein, we report a resurfacing strategy via pseudohalogen ions to mitigate detrimental halide ion migration, aiming to stabilize PNC LEDs. We employ a thiocyanate solution processed post-treatment method to efficiently resurface CsPbBr3 NCs and demonstrate that the thiocyanate ions can effectively inhibit bromide ion migration in LHP NC thin films. Owing to thiocyanate resurfacing, we fabricated LEDs with a high EQE of 17.3%, a maximum brightness of 48000 cd m-2, and an excellent operation half-life time.

Insights into effects of thermotolerant nitrifying and sulfur-oxidizing inoculants on nitrogen-sulfur co-metabolism in sewage sludge composting.

In this study, high temperature thermotolerant nitrifying bacteria (TNB) and high temperature thermotolerant sulfide oxidizing bacteria (TSOB) were obtained from compost samples and inoculated into sewage sludge (SS) compost. The effects of inoculation on physical and chemical parameters, ammonia and hydrogen sulfide release, nitrogen form and sulfur compound content change and physical-chemical properties during nitrogen and sulfur conversion were studied. The results showed that inoculation of TNB and TSOB increased the temperature, pH, OM degradation, C/N ratio and germination index (GI) of compost. Compared with the control treatment (CK), the addition of inoculants reduced the release of NH3 and H2S, and transformed them into nitrogen and sulfur compounds, the hydrolysis of polymeric ferrous sulfate was promoted, resulting in relatively high content of sulfite and sulfate. At the same time, the physical and chemical properties of SS have a strong correlation with nitrogen and sulfur compounds.

Aggregation Enhanced Thermally Activated Delayed Fluorescence through Spin-Orbit Coupling Regulation.

Integrating aggregation-induced emission (AIE) into thermally activated delayed fluorescence (TADF) emitters holds great promise for the advancement of highly efficient organic light emitting diodes (OLEDs). Despite recent advancements, a thorough comprehension of the underlying mechanisms remains imperative for the practical application of such materials. In this work, we introduce a novel approach aimed at modulating the TADF process by manipulating dynamic processes in excited states through aggregation effect. Our findings reveal that aggregation not only enhances both prompt and delayed fluorescence simultaneously but also imposes constraints on molecular reorientation. This constraint reinforces spin-orbit coupling and reduces the energy gap between singlets and triplets. These insights deepen our understanding of the fundamental mechanisms governing the aggregation effect on TADF materials and provide valuable guidance for the design of high-efficiency photoluminescent materials.

Combinatorial Drug Screening Based on Massive 3D Tumor Cultures Using Micropatterned Array Chips.

The establishment and application of a generalizable three-dimensional (3D) tumor device for high-throughput screening plays an important role in drug discovery and cancer therapeutics. In this study, we introduce a facile microplatform for considerable 3D tumor generation and combinatorial drug screening evaluation. High fidelity of chip fabrication was achieved depending on the simple and well-improved microcontact printing. We demonstrated the high stability and repeatability of the established tumor-on-a-chip system for controllable and massive production of 3D tumors with high size uniformity. Importantly, we accomplished the screening-like chemotherapy investigation involving individual and combinatorial drugs and validated the high accessibility and applicability of the system in 3D tumor-based manipulation and analysis on a large scale. This achievement in tumor-on-a-chip has potential applications in plenty of biomedical fields such as tumor biology, pharmacology, and tissue microengineering. It offers an insight into the development of the popularized microplatform with easy-to-fabricate and easy-to-operate properties for cancer exploration and therapy.

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2).

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is largely underdiagnosed and undertreated in China where few patients achieved recommended target levels of low density lipoprotein cholesterol (LDL-C). We conducted the first randomized, placebo-controlled clinical trial in Chinese patients with HeFH to assess the efficacy and safety of tafolecimab, a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody. METHODS: Patients diagnosed with HeFH by Simon Broome criteria and on a stable lipid-lowering therapy for at least 4 weeks were randomized 2:2:1:1 to receive subcutaneous tafolecimab 150 mg every 2 weeks (Q2W), tafolecimab 450 mg every 4 weeks (Q4W), placebo Q2W or placebo Q4W in the 12-week double-blind treatment period. After that, participants received open-label tafolecimab 150 mg Q2W or 450 mg Q4W for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Secondary endpoints included proportion of participants achieving ≥50% LDL-C reductions and proportion of participants with LDL-C <1.8 mmol/L at week 12 and 24, the change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and lipoprotein(a) levels, as well as the change from baseline to week 24 in lipid levels. RESULTS: In total, 149 participants were randomized and 148 received at least one dose of the study treatment. At week 12, tafolecimab treatment induced significant reductions in LDL-C levels (treatment difference versus placebo [on-treatment estimand]: -57.4% [97.5% CI, -69.2 to -45.5] for 150 mg Q2W; -61.9% [-73.4 to -50.4] for 450 mg Q4W; both P <0.0001). At both dose regimens, significantly more participants treated with tafolecimab achieved ≥50% LDL-C reductions or LDL-C <1.8 mmol/L at week 12 as compared with corresponding placebo groups (all P <0.0001). Meanwhile, non-HDL-C, apolipoprotein B and lipoprotein(a) levels were significantly reduced in the tafolecimab groups at week 12. The lipid-lowering effects of tafolecimab were maintained till week 24. During the double-blind treatment period, the most commonly-reported adverse events in the tafolecimab groups included upper respiratory tract infection, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase and hypertension. CONCLUSIONS: Tafolecimab administered either 150 mg Q2W or 450 mg Q4W yielded significant and persistent reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with HeFH. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04179669.

EREG is the core onco-immunological biomarker of cuproptosis and mediates the cross-talk between VEGF and CD99 signaling in glioblastoma.

BACKGROUND: Glioma is the most prevalent primary tumor of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant form of glioma with an extremely poor prognosis. A novel, regulated cell death form of copper-induced cell death called "cuproptosis" provides a new prospect for cancer treatment by regulating cuproptosis. METHODS: Data from bulk RNA sequencing (RNA-seq) analysis (The Cancer Genome Atlas cohort and Chinese Glioma Genome Atlas cohort) and single cell RNA-seq (scRNA-seq) analysis were integrated to reveal their relationships. A scoring system was constructed according to the cuproptosis-related gene expression, and core genes were experimentally verified using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot (WB), immunohistochemistry (IHC), and immunofluorescence (IF). Moreover, cell counting kit-8 (CCK8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, transwell, and flow cytometry cell cycle were performed to evaluate cell proliferation, invasion, and migration. RESULTS: The Cuproptosis Activation Scoring (CuAS) Model has stable and independent prognostic efficacy, as verified by two CGGA datasets. Epiregulin (EREG), the gene of the model has the most contributions in the principal component analysis (PCA), is an onco-immunological gene that can affect immunity by influencing the expression of programmed death-ligand 1 (PD-L1) and mediate the process of cuproptosis by influencing the expression of ferredoxin 1 (FDX1). Single cell transcriptome analysis revealed that high CuAS GBM cells are found in vascular endothelial growth factor A (VEGFA) + malignant cells. Oligodendrocyte transcription factor 1 (OLIG1) + malignant is the original clone, and VEGF and CD99 are the differential pathways of specific cell communication between the high and low CuAS groups. This was also demonstrated by immunofluorescence in the tissue sections. Furthermore, CuAS has therapeutic potential for immunotherapy, and we predict that many drugs (methotrexate, NU7441, KU -0063794, GDC-0941, cabozantinib, and NVP-BEZ235) may be used in patients with high CuAS. CONCLUSION: EREG is the core onco-immunological biomarker of CuAS and modulates the cross-talk between VEGF and CD99 signaling in glioblastoma, and CuAS may provide support for immunotherapy and chemotherapy.