Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism.

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.

Aging-Related CYP3A Functional Changes in Chinese Older Patients: New Findings from Model-Based Assessment of Amlodipine.

Aging-related alterations in hepatic enzyme activity, particularly of the CYP3A, significantly impact drug efficacy and safety in older adults, making it essential to understand how aging affects CYP function for optimal drug therapy. The exogenous probe substrate method, a minimally invasive approach to assess liver metabolic enzyme activity in vivo, is effective in studying these changes. Amlodipine being extensively metabolized (> 90%) in the liver, primarily via cytochrome P450 enzyme CYP3A was selected as a probe to investigate and quantify the factors affecting the aging-related changes of CYP3A in the Chinese older population. Amlodipine concentration data were collected from an ongoing noninterventional clinical study conducted at Peking University Third Hospital. A physiologically-based pharmacokinetic modeling approach, grounded in population pharmacokinetic (PPK) analysis, was employed to physiologically quantify the aging-related changes in CYP3A function. A total of 132 amlodipine concentrations from 69 patients were obtained from the clinical study. PPK analysis shows that frailty phenotype but not age is a significant influence and frail patients have 37% greater plasma amlodipine exposure than nonfrail patients. This difference in CYP3A function may be attributed to a 63.2% lower CYP3A relative abundance in the frail patients, compared with that in the nonfrail patients. In the context of dose selection for older adults, focusing on frailty rather than chronological age should be recognized as a more relevant approach, because frailty might more accurately reflect the individual's biological age. Our study suggested a need to shift the research focus from chronological age to biological age.

Revealing Enhanced Optical Nonlinearity and Robust Ferromagnetism in Atomically Sharp Stacking Binary-Ternary Magnetic Heterostructures.

Two-dimensional (2D) materials provide a versatile platform for the integration of diverse crystals, enabling the formation of heterostructures with intriguing functionalities. Coherently growing 2D heterostructures are highly desirable for property manipulation due to their strong interfacial interaction. In this work, we propose a general synthesis approach and provide insight into well-designed 2D binary-ternary magnetic heterostructures. Atomically sharp interfaces were achieved in typical lateral and vertical Cr1+mSe2(001)/CuCr2Se4(111) heterostructures owing to their similar lattice arrangement, with the observation of a significant enhancement of optical second-harmonic generation. Further magnetism measurements revealed a Curie temperature up to 360 K and thickness- and temperature-dependent magnetism in this heterostructure. Additionally, we synthesized three analogous 2D magnetic heterostructures in Fe-Cr-S, Co-Cr-S, and Cu-Cr-S systems, demonstrating the ubiquitous nature of the coherent heteroepitaxy. Our work involves the development of an innovative platform for investigating the underlying physics and potential applications of 2D binary-ternary heterostructures as well as the fabrication of associated functional devices.

Prevention of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linnén on cutaneous squamous cell carcinomas progression following UV irradiation in mice.

Chrysanthemum indicum Linnén (C. indicum), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CISCFE) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CISCFE, high concentration CISCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CISCFE. The results showed that CISCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CISCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CISCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CISCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways.

Optimization of Ultrasound-Assisted Deep Eutectic Solvent Extraction, Characterization, and Bioactivities of Polysaccharide from Pericarpium Citri Reticulatae.

The ultrasonic-assisted deep eutectic solvent method was used to extract the polysaccharides of Pericarpium Citri Reticulatae (PCRP), and the ultrasound-assisted DES extraction process was optimized by Box-Behnken response surface test using the extraction rate of the PCRP as an index; the in vitro activities of purified the PCRP(PCRPs-1) were investigated by determining the scavenging rate of DPPH• and ABTS•+ as well as by enzyme inhibition assay. The monosaccharide composition was analyzed by HPLC. The best process conditions for response surface optimization were a material-liquid ratio of 1:37 g/mL, water content of 44%, time of 89 min, and power of 320 W. The polysaccharide extraction rate was measured to be 5.41%, which was well optimized when compared with that of the ordinary aqueous extraction method of 3.92%. By α-glucosidase and α-amylase inhibition activity test, it showed that the PCRPs-1 had hypoglycemic activity. The DPPH radical scavenging activity test and ABTS + scavenging activity test indicated that the PCRPs-1 had good biological activity. Analysis of the monosaccharide fractions showed that the PCRPs-1 consisted of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, and arabinose, with molar ratios of 1:39.24:4.41:8.91:7.83:86.00:1.02:9.17. The activity studies showed that PCRPs-1 possessed certain hypoglycaemic and antioxidant activities.

Deep Learning Analysis for Predicting Tumor Spread through Air Space in Early-Stage Lung Adenocarcinoma Pathology Images.

The presence of spread through air spaces (STASs) in early-stage lung adenocarcinoma is a significant prognostic factor associated with disease recurrence and poor outcomes. Although current STAS detection methods rely on pathological examinations, the advent of artificial intelligence (AI) offers opportunities for automated histopathological image analysis. This study developed a deep learning (DL) model for STAS prediction and investigated the correlation between the prediction results and patient outcomes. To develop the DL-based STAS prediction model, 1053 digital pathology whole-slide images (WSIs) from the competition dataset were enrolled in the training set, and 227 WSIs from the National Taiwan University Hospital were enrolled for external validation. A YOLOv5-based framework comprising preprocessing, candidate detection, false-positive reduction, and patient-based prediction was proposed for STAS prediction. The model achieved an area under the curve (AUC) of 0.83 in predicting STAS presence, with 72% accuracy, 81% sensitivity, and 63% specificity. Additionally, the DL model demonstrated a prognostic value in disease-free survival compared to that of pathological evaluation. These findings suggest that DL-based STAS prediction could serve as an adjunctive screening tool and facilitate clinical decision-making in patients with early-stage lung adenocarcinoma.

Van der Waals Epitaxial Growth of Ultrathin Indium Antimonide on Arbitrary Substrates through Low-Thermal Budget.

III-V semiconductors possess high mobility, high frequency response, and detection sensitivity, making them potentially attractive for beyond-silicon electronics applications. However, the traditional heteroepitaxy of III-V semiconductors is impeded by a significant lattice mismatch and the necessity for extreme vacuum and high temperature conditions, thereby impeding their in situ compatibility with flexible substrates and silicon-based circuits. In this study, a novel approach is presented for fabricating ultrathin InSb single-crystal nanosheets on arbitrary substrates with a thickness as thin as 2.4 nm using low-thermal-budget van der Waals (vdW) epitaxy through chemical vapor deposition (CVD). In particular, in situ growth has been successfully achieved on both silicon-based substrates and flexible polyimide (PI) substrates. Notably, the growth temperature required for InSb nanosheets (240 °C) is significantly lower than that employed in back-end-of-line processes (400 °C). The field effect transistor devices based on fabricated ultrathin InSb nanosheets exhibit ultra-high on-off ratio exceeding 108 and demonstrate minimal gate leakage currents. Furthermore, these ultrathin InSb nanosheets display p-type characteristics with hole mobilities reaching up to 203 cm2 V-1 s-1 at room temperatures. This study paves the way for achieving heterogeneous integration of III-V semiconductors and facilitating their application in flexible electronics.

Rare Orbital Involvement Originating from Extranodal Marginal Zone Lymphoma.

Ocular adnexa region (OAR) primary lymphomas are uncommon, accounting for 1-2% of non-Hodgkin lymphomas and 8% of extranodal lymphomas. Extranodal marginal zone lymphoma (EMZL) originates from several epithelial tissues, including the stomach, salivary gland, lung, small intestine, thyroid gland, and ocular adnexa region. Here, we report a 66-year-old female patient who was diagnosed with EMZL of OAR. In consideration of the possible side effect of radiotherapy, such as conjunctivitis, visual acuity impairment, and even retinal complications, she received six cycles of triweekly targeted chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) without radiotherapy. Then, she remained in complete remission up to the present day.

Empyema associated with peritoneal dialysis peritonitis.

A 65-year-old woman on peritoneal dialysis (PD) was admitted due to abdominal pain with cloudy PD effluent. The white blood cell count in PD effluent was 5860/µL with 85% polymorphonuclear neutrophils. Therefore, she was clinically diagnosed with peritonitis. The cultures of PD effluent were negative. Initial abdominal computed tomography did not find suggest any intraabdominal pathology. The patient was treated with empirical intraperitoneal antibiotics. Because abdominal pain with cloudy PD effluent persisted, the PD catheter was removed eventually. The culture of the removed PD catheter grew Klebsiella pneumoniae. However, intermittent fever was noted over the following days and empyema developed approximately 2 weeks after PD catheter removal. The culture of pleural fluid also grew K. pneumoniae. Another computed tomography revealed multiple intraabdominal abscesses that was assumed to come from a complication of PD-associated peritonitis. We postulate that the empyema might be caused by transdiaphragmatic extension of the intraabdominal abscesses into the pleural space.

Spatiotemporal dual-periodic soliton pulsation in a multimode fiber laser.

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

Two-Dimensional Semiconductors and Transistors for Future Integrated Circuits.

Silicon transistors are approaching their physical limit, calling for the emergence of a technological revolution. As the acknowledged ultimate version of transistor channels, 2D semiconductors are of interest for the development of post-Moore electronics due to their useful properties and all-in-one potentials. Here, the promise and current status of 2D semiconductors and transistors are reviewed, from materials and devices to integrated applications. First, we outline the evolution and challenges of silicon-based integrated circuits, followed by a detailed discussion on the properties and preparation strategies of 2D semiconductors and van der Waals heterostructures. Subsequently, the significant progress of 2D transistors, including device optimization, large-scale integration, and unconventional devices, are presented. We also examine 2D semiconductors for advanced heterogeneous and multifunctional integration beyond CMOS. Finally, the key technical challenges and potential strategies for 2D transistors and integrated circuits are also discussed. We envision that the field of 2D semiconductors and transistors could yield substantial progress in the upcoming years and hope this review will trigger the interest of scientists planning their next experiment.

Spontaneous Skyrmion Bubbles in an Iron-Silicon Alloy with Uniaxial Magnetic Anisotropy.

The magnetic skyrmions exhibit intriguing topological behaviors, holding promise for future applications in the realm of spintronic devices. Despite recent advancements, achieving spontaneous magnetic skyrmions and topological transitions in magnets featuring uniaxial magnetic anisotropy, particularly at elevated temperatures (>100 K), remains a challenging endeavor. Here, single-crystal Fe5Si3 nanorods with the central symmetry and uniaxial magnetic anisotropy were successfully synthesized on a mica substrate through chemical vapor deposition, which exhibit a high Curie temperature (TC) of about 372 K. The real-time observation, facilitated by Lorentz transmission electron microscopy, revealed the spontaneous formation of magnetic skyrmions and evolution of domains in focused ion beam-prepared Fe5Si3 thin foils. Moreover, Fe5Si3 device transport measurements expose notable magnetoresistance (MR) effects, enabling the interchange between positive and negative MR across specific temperature settings. These results offer various potential avenues for exploring diverse topological spin textures and their formation mechanisms, indicating inventive applications for iron-silicon alloy in the realm of spintronics.

Relationship between anion gap and in-hospital mortality in intensive care patients with liver failure: a retrospective propensity score matching analysis.

OBJECTIVES: To elucidate the association between anion gap (AG) and in-hospital mortality in intensive care patients with liver failure. METHODS: Demographic and clinical characteristics of intensive care patients with liver failure in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database were collected, and binomial logistic and Cox regression was conducted to investigate the association between AG and in-hospital mortality. The area under the receiver operating characteristic (ROC) curve (AUC) was conducted to characterize the performance of AG in predicting in-hospital mortality, and was compared with the albumin corrected anion gap (ACAG) and the End-Stage Liver Disease (MELD) score. The Kaplan-Meier curve was plotted for in-hospital survival analysis of AG and patients with liver failure. The propensity score matching (PSM) analysis was performed to mitigate selection bias. RESULTS: AG was an independent risk factor for in-hospital mortality in intensive care patients with liver failure. Before PSM, the AUCs of AG, ACAG, and MELD were 0.666, 0.682, and 0.653, respectively. After PSM, the AUCs of AG, ACAG, and MELD scores were 0.645, 0.657, and 0.645, respectively, and there is no difference in the predictive performance of the three indicators upon comparison. Compared with the low-AG (≤20 mmol/L) group, the hazard ratio (HR) for in-hospital death of the high-AG (>20 mmol/L) group was determined to be 2.1472 (before PSM)/1.8890 (after PSM). CONCLUSIONS: AG is associated with in-hospital mortality in intensive care patients with liver failure and demonstrates a moderate predictive value, which is comparable to the predictive power of the MELD score. AG may serve as an indirect marker of in-hospital mortality of patients with liver failure by reflecting the degree of metabolic acidosis.

Effects of selenium-cadmium co-enriched Cardamine hupingshanensis on bone damage in mice.

Selenium (Se) and cadmium (Cd) usually co-existed in soils, especially in areas with Se-rich soils in China. The potential health consequences for the local populations consuming foods rich in Se and Cd are unknown. Cardamine hupingshanensis (HUP) is Se and Cd hyperaccumulator plant that could be an ideal natural product to assess the protective effects of endogenous Se against endogenous Cd-caused bone damage. Male C57BL/6 mice were fed 5.22 mg/kg cadmium chloride (CdCl2) (Cd 3.2 mg/kg body weight (BW)), or HUP solutions containing Cd 3.2 mg/kg BW and Se 0.15, 0.29 or 0.50 mg/kg BW (corresponding to the HUP0, HUP1 and HUP2 groups) interventions. Se-enriched HUP1 and HUP2 significantly decreased Cd-induced femur microstructure damage and regulated serum bone osteoclastic marker levels and osteogenesis-related genes. In addition, endogenous Se significantly decreased kidney fibroblast growth factor 23 (FGF23) protein expression and serum parathyroid hormone (PTH) levels, and raised serum calcitriol (1,25(OH)2D3). Furthermore, Se also regulated gut microbiota involved in skeletal metabolism disorder. In conclusion, endogenous Se, especially with higher doses (the HUP2 group), positively affects bone formation and resorption by mitigating the damaging effects of endogenous Cd via the modulation of renal FGF23 expression, circulating 1,25(OH)2D3 and PTH and gut microbiota composition.

van der Waals Epitaxial Growth of One-Unit-Cell-Thick Ferroelectric CuCrS2 Nanosheets.

Ferroelectric two-dimensional (2D) materials with a high transition temperature are highly desirable for new physics and next-generation memory electronics. However, the long-range polar order of ferroelectrics will barely persist when the thickness reaches the nanoscale. In this work, we synthesized 2D CuCrS2 nanosheets with thicknesses down to one unit cell via van der Waals epitaxy in a chemical vapor deposition system. A combination of transmission electron microscopy, second-harmonic generation, and Raman spectroscopy measurements confirms the R3m space group and noncentrosymmetric structure. Switchable ferroelectric domains and obvious ferroelectric hysteresis loops were created and visualized by piezoresponse force microscopy. Theoretical calculation helps us understand the mechanism of ferroelectric switching in CuCrS2 nanosheets. Finally, we fabricated a ferroelectric memory device that achieves an on/off ratio of ∼102 and remains stable after 2000 s, indicating its applicability in novel nanoelectronics. Overall, 2D CuCrS2 nanosheets exhibit excellent ferroelectric properties at the nanoscale, showing great promise for next-generation devices.

Periodically tunable multimode soliton pulsation in a spatiotemporal mode-locked fiber laser.

Multimode fiber lasers have become a new platform for investigating nonlinear phenomena since the report on spatiotemporal mode-locking. In this work, the multimode soliton pulsation with a tunable period is achieved in a spatiotemporal mode-locked fiber laser. It demonstrates that the pulsation period drops while increasing the pump power. Moreover, it is found that different transverse modes have the same pulsation period, asynchronous pulsation evolution and different dynamical characteristics through the spatial sampling technique and the dispersive Fourier transform technique. To further verify the experimental results, we numerically investigate the influences of the gain and the loss on the pulsation properties. It is found that within a certain parameter range, the pulsation period drops and rises linearly with the increase of the gain and the loss, respectively. The obtained results contribute to understanding the formation and regulating of soliton pulsations in fiber lasers.

Protective effects and mechanism of chemical- and plant-based selenocystine against cadmium-induced liver damage.

Although selenium (Se) and cadmium (Cd) often coexist naturally in the soil of China, the health risks to local residents consuming Se-Cd co-enriched foods are unknown. In the present study, we investigated the effects of chemical-based selenocystine (SeCys2) on cadmium chloride-induced human hepatocarcinoma (HepG2) cell injury and plant (Cardamine hupingshanensis)-derived SeCys2 against Cd-induced liver injury in mice. We found that chemical- and plant-based SeCys2 showed protective effects against Cd-induced HepG2 cell injury and liver damage in mice, respectively. Compared with Cd intervention group, co-treatment with chemical- or plant-based SeCys2 both alleviated liver toxicity and ferroptosis by decreasing ferrous iron, acyl-CoA synthetase long-chain (ACSL) family member 4, lysophosphatidylcholine acyltransferase 3, reactive oxygen species and lipid peroxide levels, and increasing ACSL3, peroxisome proliferator-activated receptor α, solute carrier family 7 member 11 (SLC7A11) and glutathione and glutathione peroxidase 4 (GPX4) levels. In conclusion, chemical- and plant-based SeCys2 alleviated Cd-induced hepatotoxicity and ferroptosis by regulating SLC7A11/GPX4 signaling and lipid peroxidation. Our findings indicate that potential Cd toxicity from consuming foods grown in Se- and Cd-rich soils should be re-evaluated. This study offers a new perspective for the development of SeCys2-enriched agricultural products.

Wearable Sensor Based on a Tough Conductive Gel for Real-Time and Remote Human Motion Monitoring.

The usage of a conductive hydrogel in wearable sensors has been thoroughly researched recently. Nonetheless, hydrogel-based sensors cannot simultaneously have excellent mechanical property, high sensitivity, comfortable wearability, and rapid self-healing performance, which result in poor durability and reusability. Herein, a robust conductive hydrogel derived from one-pot polymerization and subsequent solvent replacement is developed as a wearable sensor. Owing to the reversible hydrogen bonds cross-linked between polymer chains and clay nanosheets, the resulting conductive hydrogel-based sensor exhibits outstanding flexibility, self-repairing, and fatigue resistance performances. The embedding of graphene oxide nanosheets offers an enhanced hydrogel network and easy release of wearable sensor from the target position through remote irradiation, while Li+ ions incorporated by solvent replacement endow the wearable sensor with low detection limit (sensing strain: 1%), high conductivity (4.3 S m-1) and sensitivity (gauge factor: 3.04), good freezing resistance, and water retention. Therefore, the fabricated wearable sensor is suitable to monitor small and large human motions on the site and remotely under subzero (-54 °C) or room temperature, indicating lots of promising applications in human-motion monitoring, information encryption and identification, and electronic skins.

Two-Dimensional Oxide Crystals for Device Applications: Challenges and Opportunities.

Atomically thin two-dimensional (2D) oxide crystals have garnered considerable attention because of their remarkable physical properties and potential for versatile applications. In recent years, significant advancements have been made in the design, preparation, and application of ultrathin 2D oxides, providing many opportunities for new-generation advanced technologies. This review focuses on the controllable preparation of 2D oxide crystals and their applications in electronic and optoelectronic devices. Based on their bonding nature, the various types of 2D oxide crystals are first summarized, including both layered and nonlayered crystals, as well as their current top-down and bottom-up synthetic approaches. Subsequently, in terms of the unique physical and electrical properties of 2D oxides, recent advances in device applications are emphasized, including photodetectors, field-effect transistors, dielectric layers, magnetic and ferroelectric devices, memories, and gas sensors. Finally, conclusions and future prospects of 2D oxide crystals are presented. It is hoped that this review will provide comprehensive and insightful guidance for the development of 2D oxide crystals and their device applications.

Palmoplantar pustulosis with psoriatic arthritis ineffective to interleukin-17 inhibitors: two patients successfully treated with upadacitinib.

Palmoplantar pustulosis (PPP) is a rare chronic pustular disease. Psoriatic arthritis (PsA) is one of the common manifestations of arthritis in PPP associated with a high burden of disease. The treatment of PPP is difficult and still in the exploratory stage. Only a few cases show that PPP complicated with arthritis have been successfully treated with janus kinase inhibition, interleukin (IL)-6 inhibitors, IL-12/23 inhibitors and tumor necrosis factor inhibitors. Here we reported that two patients were diagnosed as PPP with PsA and initially treated with IL-17 inhibitors. One case was only partially relieved, and the other case had severe paradoxical reaction in the trunk. The joint and skin condition of two patients had been significantly improved without reported adverse reactions after 18 weeks treatment with upadacitinib, which support upadacitinib may be a potential option for patients with PPP combined PsA.