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Pin Wang,1– 4 Jia-Zheng Sun,3,4 Hui-Ying Fang,3,4 De-Juan Yang,3,4 Guo-Sheng Ren3,4 1Department of General Surgery, the Third People’s Hospital of Chengdu, Chengdu, People’s Republic of China; 2Center of Breast and Thyroid Surgery, the Third People’s Hospital of Chengdu, Chengdu, People’s Republic of China; 3Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Pin Wang, Email wangpin109@126.comBackground: Idiopathic granulomatous mastitis (IGM) is a chronic breast condition known for its aggressive nature and tendency for persistence and recurrence. Steroids are commonly used as the first-line treatment for IGM, but issues such as the optimal timing, and duration of treatment remain debated.Methods: We retrospectively analyzed 343 IGM cases treated at the Third People’s Hospital of Chengdu from September 2012 to September 2023. Based on inclusion and exclusion criteria, a total of 188 patients were included in the study. Patients were categorized into lump (78 cases), abscess (81 cases), and sinus tract stages (29 cases) according to their initial diagnosis upon admission. Prednisolone was initiated at 0.75 mg/kg/day, and after effective treatment, the dosage was adjusted by 5– 10 mg weekly, followed by a maintenance dose of 2.5– 5 mg/day. Clinical characteristics, treatment responses, adverse effects, recurrence rates, and follow-up data were assessed.Results: The median duration of prednisone treatment in our study was 87 days (range, 21– 281 days). Positive response rates to prednisolone were 78.2% in the lump stage, 60.5% in the abscess stage, and 62.1% in the sinus tract stage. Continuing low-dose prednisone for 3 months post-effective treatment reduced recurrence rates and side effect risks. Weight gain was the most common side effect (39.36%).Conclusion: Early steroid therapy, especially in the lump stage, demonstrated superior efficacy. Following a regimen of starting with a full dose, tapering slowly, and maintaining a low dose for around 3 months steroids treatment is recommended to minimize recurrence rate and adverse effects.Keywords: Idiopathic Granulomatous Mastitis (IGM), Steroids, Breast, Prednisolone

Du-Jiang Yang,1,* Jun-Jie Xiong,1,* Xue-Ting Liu,2 Jiao Li,3 Kanagarathna Mudiyanselage Dhanushka Layanthi Siriwardena,4 Wei-Ming Hu11Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, People’s Republic of China; 2Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, People’s Republic of China; 3Department of Emergency, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, People’s Republic of China; 4West China School of Medicine, Sichuan University, Chengdu 610041, Sichuan Province, People’s Republic of China *These authors contributed equally to this work Aim: To assess whether total pancreatectomy (TP) is as feasible, safe, and efficacious as pancreaticoduodenectomy (PD).Materials and Methods: Major databases, including PubMed, EMBASE, Science Citation Index Expanded, Scopus and the Cochrane Library, were searched for studies comparing TP and PD between January 1943 and June 2018. The meta-analysis only included studies that were conducted after 2000. The primary outcomes were morbidity and mortality. Pooled odds ratios (ORs), weighted mean differences (WMDs) or hazard ratios (HRs) with 95 percent confidence intervals (CIs) were calculated using fixed effects or random effects models. The methodological quality of the included studies was evaluated by the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool.Results: In total, 45 studies were included in this systematic review, and 5 non-randomized comparative studies with 786 patients (TP: 270, PD: 516) were included in the meta-analysis. There were no differences in terms of mortality (OR: 1.44, 95% CI: 0.66–3.16; P=0.36), hospital stay (WMD: −0.60, 95% CI: −1.78–0.59; P=0.32) and rates of reoperation (OR: 1.12; 95% CI: 0.55–2.31; P=0.75) between the two groups. In addition, morbidity was not significantly different between the two groups (OR: 1.41, 95% CI: 1.01–1.97; P=0.05); however, the results showed that the TP group tended to have more complications than the PD group. Furthermore, the operation time (WMD: 29.56, 95% CI: 8.23–50.89; P=0.007) was longer in the TP group. Blood loss (WMD: 339.96, 95% CI: 117.74–562.18; P=0.003) and blood transfusion (OR: 4.86, 95% CI: 1.93–12.29; P=0.0008) were more common in the TP group than in the PD group. There were no differences in the long-term survival rates between the two groups.Conclusion: This systematic review and meta-analysis suggested that TP may not be as feasible and safe as PD. However, TP and PD may have the same efficacy.Keywords: total pancreatectomy, pancreaticoduodenectomy, morbidity, mortality, meta-analysis

Rationale and Objectives: Radiolabeled tyrosine analogues that have been successfully used in tumor imaging accumulate in tumor cells via an upregulated L-type amino acid transporter system. The anticancer drug melphalan is an L-type amino acid transporter substrate. Therefore, radiolabeled tyrosine analogues may have great potential in evaluating treatment responses to melphalan. In this study, a (99m)Tc-labeled tyrosine analogue, (99m)Tc tyrosine using N,N'-ethylene-di-L-cysteine (EC) as a chelator, was developed and its potential for noninvasively assessing tumors' early response to melphalan determined.Materials and Methods: EC-tyrosine was synthesized in a three-step procedure and labeled with (99m)Tc. To assess cellular uptake kinetics, the percentage uptake of (99m)Tc-EC-tyrosine in the rat breast cancer cell line 13762 was measured. Planar imaging was performed in rats with 13762 cell-derived tumors. To determine the transport mechanisms of (99m)Tc-EC-tyrosine, a competitive inhibition study using L-tyrosine as an inhibitor was performed in vitro and in vivo. To assess tumors' response to melphalan, tumor-bearing rats were treated with different doses of melphalan, and planar imaging was performed 0 and 3 days after treatment. Immunohistochemical analyses were conducted to determine expressions of L-type amino acid transporter 1 and cellular proliferation marker Ki-67.Results: L-tyrosine significantly inhibited (99m)Tc-EC-tyrosine uptake in vitro and in vivo. Tumor volume decreased in a dose-dependent manner with melphalan, and tumor/muscle ratios of (99m)Tc-EC-tyrosine were significantly reduced in treated groups. Immunohistochemical data indicated that about 70% of tumor cells in the melphalan-treated groups underwent apoptosis, and the changes in tumor/muscle ratios reflected the decreased percentage of viable cells in treated tumors.Conclusions: These findings suggest that (99m)Tc-EC-tyrosine has great potential for monitoring tumor response to melphalan in breast tumor-bearing rats. [ABSTRACT FROM AUTHOR]

Noni juice (NJ) is rich in phytochemicals and polysaccharides. Lipid-lowering and antioxidative effects of NJ were investigated in this study. Fifty male hamsters were assigned randomly to one of the following groups: (1) normal diet and distilled water (LFCD); (2) high-fat/cholesterol diet and distilled water (HFCD); (3) HFCD and 3 ml NJ (including 0.20 g solids)/kg BW (NJ_L); (4) HFCD and 6 mL NJ (including 0.40 g solids)/kg BW (NJ_M); (5) HFCD and 9 ml NJ (including 0.60 g solids)/kg BW (NJ_H) for six weeks. NJ supplementation decreased (p < 0.05) serum triacylglycerol, cholesterol, atherogenic index, malondialdehyde levels, and hepatic lipids in HFCD hamsters, whereas serum trolox equivalent antioxidant capacity, glutathione, and fecal lipids in HFCD hamsters were increased (p < 0.05) by NJ supplementation. Although NJ supplementation downregulated (p < 0.05) sterol regulator element binding protein-1c in HFCD hamsters, it upregulated (p < 0.05) hepatic peroxisome proliferator-activated receptor-alpha and uncoupling protein 2 gene expressions in HFCD hamsters. Results demonstrate that NJ promotes cardioprotection in a high-fat/cholesterol diet. [ABSTRACT FROM AUTHOR]

Objective: This study was aimed to assess pancreas beta cell activity using (99m)Tc-diethyleneaminepentaacetic acid-glipizide (DTPA-GLP), a sulfonylurea receptor agent. The effect of DTPA-GLP on the blood glucose level in rats was also evaluated.Methods: DTPA dianhydride was conjugated with GLP in the presence of sodium amide, yielding 60%. Biodistribution and planar images were obtained at 30-120 min after injection of (99m)Tc-DTPA-GLP (1 mg/rat, 0.74 and 11.1 MBq per rat, respectively) in normal female Fischer 344 rats. The control group was given (99m)Tc-DTPA. To demonstrate pancreas beta cell uptake of (99m)Tc-DTPA-GLP via a receptor-mediated process, a group of rats was pretreated with streptozotocin (a beta cell toxin, 55 mg/kg, i.v.) and the images were acquired at immediately-65 min on day 5 post-treatment. The effect on the glucose levels after a single administration (ip) of DTPA-GLP was compared to glipizide (GLP) for up to 6 h.Results: The structure of DTPA-GLP was confirmed by NMR, mass spectrometry and HPLC. Radiochemical purity assessed by ITLC was >96%. (99m)Tc-DTPA-GLP showed increased pancreas-to-muscle ratios, whereas (99m)Tc-DTPA showed decreased ratios at various time points. Pancreas could be visualized with (99m)Tc-DTPA-GLP in normal rat, however, (99m)Tc-DTPA has poor uptake suggesting the specificity of (99m)Tc-DTPA-GLP. Pancreas beta cell uptake could be blocked by pre-treatment with streptozotocin. DTPA-GLP showed an equal or better response in lowering the glucose levels compared to the existing GLP drug.Conclusions: It is feasible to use (99m)Tc-DTPA-GLP to assess pancreas beta cell receptor recognition. (99m)Tc-DTPA-GLP may be helpful in evaluating patients with diabetes, pancreatitis and pancreatic tumors. [ABSTRACT FROM AUTHOR]

Background: Ceratocystis fimbriata is a fungal pathogen that infects sweet potato roots, producing enormous economic losses. Cyclic polyhydroxy compound quinic acid is a common metabolite synthesized in plant tissues, including sweet potato tubers, showing weak antifungal properties. Although several O-acylated quinic acid derivatives have been synthesized and found in nature and their antifungal properties have been explored, derivatives based on modification of the carboxylic acid have never been evaluated., Results: In this study, amide derivatives were synthesized via linkage of amines with the carboxylic acid moiety of quinic acid. Derivatives with high dipolar moments and a low number of rotatable bonds showed greater antifungal activities toward C. fimbriata in vitro than quinic and chlorogenic acids. Derivative 5b, which was synthesized by coupling p-aminobenzoic acid (pABA) with quinic acid, had the greatest antifungal activity. 5b showed iron(II)-chelating properties and reduced ergosterol content in C. fimbriata cells, causing irregularities in the fungal cell wall and inhibiting conidia agglutination. Application of 3 mm 5b reduced black rot symptoms in sweet potatoes by 70.1%., Conclusions: Collectively, derivatization of the carboxylic acid from quinic acid was demonstrated to be a suitable strategy to improve the antifungal properties of this compound. This study reveals a new efficient strategy for management of the sweet potato pathogen C. fimbriata. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Copper (Cu) is currently the dominant interconnect material in back-end-of-line processes due to its low bulk resistivity (ρ 0 ). Unfortunately, its resistivity increases significantly at small dimensions due to a long electron mean free path (EMFP, λ) of 39 nm, which leads to enhanced electron scattering at grain boundaries and surfaces, thereby limiting high-density integration. In this study, we demonstrate that single-phase hexagonal-close-packed (HCP) nickel-cobalt (NiCo) alloy thin films exhibit a significantly reduced resistivity size effect, outperforming Cu interconnect material for thicknesses below 8 nm (19.83 μΩ·cm at 4.9 nm). First-principles calculations predicted a lower ρ 0 ·λ of 5.68 × 10 - 16 Ω m 2 for HCP NiCo ( xx ) than to Cu (6.73 × 10 -16 Ω m 2 ), due to a significant contribution from the short EMFP of approximately 5 nm in the HCP NiCo alloy. To date, the growth of single-phase HCP NiCo film had not been achieved, as both HCP and face-centered-cubic (FCC) phases coexist at Co concentration of 50-80 atom %. However, single-phase HCP NiCo films were successfully grown by using an HCP Co seed layer, which reduced the lattice mismatch with the sapphire (0001) substrate. Moreover, NiCo thin films can be successfully dry etched, providing a significant advantage in device fabrication, since it does not require a damascene process unlike Cu. The NiCo thin films also exhibited high thermal stability above 500 °C. Therefore, HCP NiCo is considered a promising alternative to overcome the scaling limitations of Cu interconnects.

Conditions were determined for rapid, convenient, and efficient determination of 16 common mycotoxins in tea samples. Mycotoxins in tea leaves and tea infusion samples were extracted using solid-liquid extraction/liquid-liquid extraction combined with ultrasonic-assisted extraction. The extraction solvent was 2-butanone/ethyl acetate (9/1 v/v) with 0.1 % formic acid. The established conditions enabled the analysis of these mycotoxins by ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) in 5.5 min. In addition, HPLC with a temperature-controlled fluorescence detector was able to simultaneously determine 8 mycotoxins with fluorescent properties in 10 min without derivatization. Aflatoxin M1 (2.15 and 3.01 μg/kg), fumonisin B2 (198.89 μg/kg), and zearalenone (87.54 μg/kg) could be detected in commercially available pu-erh tea, green tea, and black tea products, and their total transfer rates from the products to brewed tea infusions were 64.08-65.13 %, 90.59 %, and 25.99 %, respectively. The risks of drinking mycotoxins from these tea infusions mostly showed low levels of concern., Competing Interests: Declaration of competing interest The authors have declared that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

The advancement in semiconductor technology through the integration of more devices on a chip has reached a point where device scaling alone is no longer an efficient way to improve the device performance. One issue lies in the interconnects connecting the transistors, in which the resistivity of metals increases exponentially as their dimensions are scaled down to match those of the transistors. As a result, the total signal processing delay is dominated by the resistance-capacitance (RC) delay from the interconnects rather than the delay from the transistors' switching speed. This bottleneck has spurred efforts both in academia and industry to explore alternative materials and disruptive device structures. Therefore, we suggest strategies to overcome the RC delay of the interconnects in both material and device aspects.

Nicotine is an alkaloid found in tobacco. Human exposure to nicotine primarily occurs through the use of tobacco products. To date, limited nicotine pharmacokinetic data in animals have been reported. This study exposed male Sprague-Dawley rats to vehicle (and/or air) or 4 doses of nicotine via nose-only inhalation (INH), oral gavage (PO), and intravenous (IV) infusion. Plasma, 6 tissues (brain, heart, lung, liver, kidney, and muscle), and urine were collected at multiple timepoints from 5 min to 48 h post-dose. The concentrations of nicotine, cotinine, and trans-3'-hydroxycotinine (3-OH-cotinine) were determined, and the pharmacokinetic profiles were compared among the 4 doses for each route. The results indicated that after single nicotine dose, nicotine bioavailability was 53% via PO. Across all the administration routes and doses, nicotine was quickly distributed to all 6 tissues; kidney had the highest nicotine and cotinine levels, and the lung had the highest 3-OH-cotinine levels; nicotine was metabolized extensively to cotinine and cotinine was metabolized to a lesser extent to 3-OH-cotinine; the elimination of plasma nicotine, cotinine, and 3-OH-cotinine followed first-order kinetics; plasma nicotine had a shorter half-life than cotinine or 3-OH-cotinine; the half-lives of plasma nicotine, cotinine, and 3-OH-cotinine were dose- and route-independent; and nicotine and cotinine were major urinary excretions followed by 3-OH-cotinine. Nicotine, cotinine, and 3-OH-cotinine levels in plasma, tissues, and urine exhibited dose-dependent increases. These study findings improve our understanding of the pharmacokinetics of nicotine, cotinine, and 3-OH-cotinine across different routes of exposure., (Published by Oxford University Press on behalf of the Society of Toxicology 2024.)

Vascular endothelial inflammation is crucial in hepatic ischemia-reperfusion injury (IRI). Our previous research has shown that connective tissue growth factor (CTGF), secreted by endothelial cells, protects against acute liver injury, but its upstream mechanism is unclear. We aimed to clarify the protective role of CTGF in endothelial cell inflammation during IRI and reveal the regulation between endoplasmic reticulum stress-induced activating transcription factor 6 (ATF6) and CTGF. Hypoxia/reoxygenation in endothelial cells, hepatic IRI in mice and clinical specimens were used to examine the relationships between CTGF and inflammatory factors and determine how ATF6 regulates CTGF and reduces damage. We found that activating ATF6 promoted CTGF expression and reduced liver damage in hepatic IRI. In vitro, activated ATF6 upregulated CTGF and downregulated inflammation, while ATF6 inhibition had the opposite effect. Dual-luciferase assays and chromatin immunoprecipitation confirmed that activated ATF6 binds to the CTGF promoter, enhancing its expression. Activated ATF6 increases CTGF and reduces extracellular regulated protein kinase 1/2 (ERK1/2) phosphorylation, decreasing inflammatory factors. Conversely, inhibiting ATF6 decreases CTGF and increases the phosphorylation of ERK1/2, increasing inflammatory factor levels. ERK1/2 inhibition reverses this effect. Clinical samples have shown that CTGF increases after IRI, inversely correlating with inflammatory cytokines. Therefore, ATF6 activation during liver IRI enhances CTGF expression and reduces endothelial inflammation via ERK1/2 inhibition, providing a novel target for diagnosing and treating liver IRI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To compare the long-term prognostic effect of complete percutaneous coronary intervention (PCI) on cardiovascular events in chronic total occlusion (CTO) patients with the multi-vessel disease (MVD) compared with medical therapy (MT). We enrolled 441 patients with CTO and MVD who underwent PCI. The study population was divided into the CTO-PCI (n = 231) and the CTO-MT (n = 210) groups. Active PCI for non-CTO lesions was permitted in both groups. The primary endpoint was defined as the composite of all-cause death or myocardial infarction (MI). The primary endpoint occurred more frequently in the CTO-MT group (13.5%) than in the CTO-PCI group (4.7%; P = 0.002). However, the target vessel revascularization (TVR), as a secondary endpoint, occurred more in the CTO-PCI group (16.3% vs. 5.5%, P = 0.001). After propensity score matching (PSM) analysis, the primary endpoint was higher in the CTO-MT group (12.6%) than in the PCI group (2.3%): all-cause death (8.4% vs. 2.3%, P = 0.042) and MI (4.3% vs. 0.0%, P = 0.023). Moreover, TVR of the CTO lesions occurred more frequently in the CTO-PCI group (18.1% vs. 6.8%, P = 0.009). Significant improvement in the left ventricular ejection fraction (LVEF) was observed in both groups. According to the results of the subgroup analysis, CTO-PCI may be more effective in patients with diabetes, preserved LVEF (> 50%), and well-developed collateral vessels (> grade II). In this study, complete revascularization in CTO with MVD reduced the incidence of all-cause death, MI, and a composite of both over a 5 year follow-up compared to medical treatment for CTO lesions., Competing Interests: Declarations. Conflict of interest: The authors have no financial conflicts of interest., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Understanding the interaction between light and chiral nanostructures is of fundamental importance, yet the principles governing chiral interactions have remained largely phenomenological. In this work, we present a chiral field-mode (FM) matching model to quantify the circular dichroism (CD) and helical dichroism (HD) of chiral plasmonic nanostructures interacting with beams of different spin-orbit states. The chiral FM matching model posits that among the inherent resonance modes within the nanostructure, the most efficiently excited mode is the one that matches the external field structure by possessing one more node along the vibration direction, with the field structure itself being determined by the interaction between the geometric phase and dynamic phase through a Doppler-like effect. The geometric phase in this model is well-defined by the product of the winding angle of the nanohelix and the angular momenta of light, including both its spin and orbital components. Thus, the beams of different spin-orbit states excite the specific resonance mode possessing one more node compared with the field structure, resulting in the spin-related CD and orbit-related HD. This model is extended to various chiral nanocomplexes, demonstrating how the field structure determines mode excitation and offering a comprehensive explanation for the CD and HD observed in various experimental setups. This model offers insights into the CD and HD microscopy in chiral nanostructures, contributing to the advancement of the fundamental theory of chiral nanophotonics.

HER2-positive gastric cancer has a poor prognosis, with a high incidence of drug resistance and a lack of effective treatments for drug-resistant patients. The exploration of the mechanism of resistance to HER2-targeted therapy in HER2-positive gastric cancer and the identification of effective strategies to reverse it are urgently needed. In this study, we found that HER2-targeted agents upregulated the expression of GSDME and that the overexpression of GSDME attenuated the sensitivity of HER2-targeted agents. Furthermore, we observed that the BCL-2/BCL-XL inhibitor APG-1252 plus lapatinib promoted GSDME-mediated pyroptosis and exhibited remarkable antitumor activity both in vitro and in vivo. Mechanistically, APG-1252 combined with lapatinib synergistically induced GSDME-mediated pyroptosis in HER2-positive gastric cancer by activating caspase-dependent pathways and blocking the phospho-AKT/GSK-3β/MCL-1 signaling pathway. Our data indicated that the combination of lapatinib and APG-1252 had a synergistic antitumor effect on HER2-positive gastric cancer through the induction of caspase-3/GSDME-mediated apoptosis and pyroptosis., Competing Interests: Competing interests: DJY holds ownership interests, including patents, in Ascentage Pharma Group Corp. Limited. WTP is an employee of Ascentage Pharma Group Corp. Limited. The remaining authors have no potential conflicts of interest to disclose. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethical Review Committee of Sun Yat-sen University Cancer Center (B2022-633-01). Informed written consent was obtained from all participants. The in vivo animal experiments were approved by the animal experimentation ethics committee and carried out under the guidance of the Sun Yat-Sen University Committee for the Use and Care of Laboratory Animals (Approval number: L102012022110I). Consent for Publication: All the authors have read and approved the manuscript., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Plant-derived extracellular vesicles (PDEVs) are nanoscale vesicles released from plant cells into the extracellular space. While similar in structure and function to mammalian-derived EVs, PDEVs are unique due to their origin and the specific metabolites they carry. PDEVs have gained significant attention in recent years, with numerous reports isolating different PDEVs from various plants, each exhibiting diverse biological functions. However, the field is still in its early stages, and many issues need further exploration. To better develop and utilize PDEVs, it is essential to have a comprehensive understanding of their characteristics. This review provides an overview of recent advances in PDEV research. It focuses on the methods and techniques for isolating and purifying PDEVs, comparing their respective advantages, limitations, and application scenarios. Furthermore, we discuss the latest discoveries regarding the composition of PDEVs, including lipids, proteins, nucleic acids, and various plant metabolites. Additionally, we detail advanced studies on the multiple biological functions of PDEVs. Our goal is to advance our understanding of PDEVs and encourage further exploration in PDEV-based science and technology, offering insights into their potential applications for human health.

Targeted radionuclide therapy (TRT) for internal pathway-directed treatment is a game changer for precision medicine. TRT improves tumor control while minimizing damage to healthy tissue and extends the survival for patients with cancer. The application of theranostic-paired TRT along with cellular phenotype and genotype correlative analysis has the potential for malignant disease management. Chelation chemistry is essential for the development of theranostic-paired radiopharmaceuticals for TRT. Among image-guided TRT, 68 Ga and 99m Tc are the current standards for diagnostic radionuclides, while 177 Lu and 225 Ac have shown great promise for β- and α-TRT, respectively. Their long half-lives, potent radiobiology, favorable decay schemes, and ability to form stable chelation conjugates make them ideal for both manufacturing and clinical use. The current challenges include optimizing radionuclide production processes, coordinating chelation chemistry stability of theranostic-paired isotopes to reduce free daughters [this pertains to 225 Ac daughters 221 Fr and 213 Bi]-induced tissue toxicity, and improving the modeling of micro dosimetry to refine dose-response evaluation. The empirical approach to TRT delivery is based on standard radionuclide administered activity levels, although clinical trials have revealed inconsistent outcomes and normal-tissue toxicities despite equivalent administered activities. This review presents the latest optimization methods for chelation-based theranostic radiopharmaceuticals, advancements in micro-dosimetry, and SPECT/CT technologies for quantifying whole-body uptake and monitoring therapeutic response as well as cytogenetic correlative analyses.

Polycyclic aromatic hydrocarbons (PAHs), carcinogenic substances primarily formed through pyrolysis and oxidation of fat at high cooking temperatures, are commonly found at high levels in grilled meats. Reducing PAHs formation by incorporating natural antioxidants, such as through marination, has been demonstrated to be effective. However, the inhibitory effect of fresh phenolic-rich fruit powders on PAHs formation in charcoal-grilled meats remains unknown. To clarify the application of the fruit powders, 15 experimental groups were conducted. All pretreatment techniques (spraying, marinating, and mixing) were applied across all four freeze-dried fruit powders (lemon, guava, papaya, and mango). Each method was systematically tested with each fruit powder to evaluate its effect on inhibiting the formation of the four PAHs (BaA, CHR, BbF, and BaP) in charcoal-grilled pork belly and loin. Firstly, guava powder exhibited the highest phenolic content and antioxidant activity compared to the lemon, papaya, and mango powders ( p < 0.05), among which the main phenolic compounds were ellagic acid, quercetin, and epigallocatechin gallate (EGCG). Further, marination of pork belly with guava powder exhibited the highest inhibition rate of PAHs (94.8%), followed by lemon (91.1%), papaya (89.8%), and mango (89.0%), with a statistically significant difference at p < 0.05. The reduction in estimated daily intake (EDI) and the increase in the margin of exposure (MOE) indicate that consuming grilled meat treated with these fruit powders poses no safety concerns and may potentially reduce health risks. Finally, the sensory evaluation showed that marinating with guava powder did not perceptibly affect the sensory attributes of the meat. Overall, this study provides a potent strategy for inhibiting the formation of PAHs in meat during charcoal grilling by incorporating fruit powder while preserving sensory qualities., Competing Interests: The authors declare no conflicts of interest.

Backgruound: Phosphatidylinositol 3-kinase (PI3K) regulates cellular development and energy homeostasis. However, the roles of its subunits in organ development remain largely unknown., Methods: We explored the roles of PI3K catalytic subunits in steroidogenic factor 1 (SF1)-expressing cells through knockout (KO) of the p110α and p110β subunits., Results: We examined mice with a double KO of p110α and p110β in SF1-expressing cells (p110αβ KOSF1). Although these animals exhibited no significant changes in the development of the ventromedial hypothalamus, we noted pronounced hypotrophy in the adrenal cortex, testis, and ovary. Additionally, corticosterone and aldosterone levels were significantly reduced. The absence of these subunits also resulted in decreased body weight and survival rate, along with impaired glucose homeostasis, in p110αβ KOSF1 mice., Conclusion: The data demonstrate the specific roles of PI3K catalytic subunits in the development and function of SF1-expressing organs.

Background and Purpose: Liver cancer is the fourth leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. APG-1252 is a small molecule inhibitor targeting Bcl-2 and Bcl-xl. However, its anti-tumor effects in HCC, alone or in combination with Cabozantinib, have not been extensively studied., Experimental: Approach: TCGA database analysis was used to analysis the gene expression levels of Bcl-2 and Bcl-xl in HCC tissues. Western blot was employed to detect the protein expression levels. And the inhibitory effects of APG-1252 and Cabozantinib on the proliferation of HCC cell lines was detected by CCK-8. The effect on the migration and invasion of HCC cells was verified by transwell assay. Huh7 xenograft model in nude mice was used to investigate the combination antitumor effect in vivo., Key Results: Our study demonstrated that APG-1252 monotherapy inhibited the proliferation and migration ability of HCC cells, and induced HCC cells apoptosis. The combination of APG-1252 and Cabozantinib showed significant synergistic antitumor effects. Furthermore, the in vivo experiment demonstrated that the combination therapy exerted a synergistic effect in delaying tumor growth, notably downregulating MEK/ERK phosphorylation levels. In terms of mechanism, Cabozantinib treatment caused an increase in the phosphorylation levels of CREB and Bcl-xl proteins, while the combination with APG-1252 mitigated this effect, thereby enhanced the antitumor effect of Cabozantinib., Conclusion and Implications: Our findings suggest that APG-1252 in combination with Cabozantinib offers a more effective treatment strategy for HCC patients, warranting further clinical investigation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

End-ischemic normothermic mechanical perfusion (NMP) could provide a curative treatment to reduce cholestatic liver injury from donation after circulatory death (DCD) in donors. However, the underlying mechanism remains elusive. Our previous study demonstrated that air-ventilated NMP could improve functional recovery of DCD in a preclinical NMP rat model. Here, metabolomics analysis revealed that air-ventilated NMP alleviated DCD- and cold preservation-induced cholestatic liver injury, as shown by the elevated release of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and γ-glutamyl transferase (GGT) in the perfusate (p < .05) and the reduction in the levels of bile acid metabolites, including ω-muricholic acid, glycohyodeoxycholic acid, glycocholic acid, and glycochenodeoxycholate (GCDC) in the perfused livers (p < .05). In addition, the expression of the key bile acid metabolism enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is predominantly expressed in hepatocytes, was substantially elevated in the DCD rat liver, followed by air-ventilated NMP (p < .05), and in vitro, this increase was induced by decreased GCDC and hypoxia-reoxygenation in the hepatic cells HepG2 and L02 (p < .05). Knockdown of UGT1A1 in hepatic cells by siRNA aggravated hepatic injury caused by GCDC and hypoxia-reoxygenation, as indicated by the ALT and AST levels in the supernatant. Mechanistically, UGT1A1 is transcriptionally regulated by peroxisome proliferator-activator receptor-γ (PPAR-γ) under hypoxia-physoxia. Taken together, our data revealed that air-ventilated NMP could alleviate DCD- and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis. Based on the results from this study, air-ventilated NMP confers a promising approach for predicting and alleviating cholestatic liver injury through PPAR-γ/UGT1A1 axis., (© 2024 Federation of American Societies for Experimental Biology.)

Background: High expression of ubiquitin ligase MDM2 is a primary cause of p53 inactivation in many tumors, making it a promising therapeutic target. However, MDM2 inhibitors have failed in clinical trials due to p53-induced feedback that enhances MDM2 expression. This underscores the urgent need to find an effective adaptive genotype or combination of targets., Methods: Kinome-wide CRISPR/Cas9 knockout screen was performed to identify genes that modulate the response to MDM2 inhibitor using TP53 wild type cancer cells and found ULK1 as a candidate. The MTT cell viability assay, flow cytometry and LDH assay were conducted to evaluate the activation of pyroptosis and the synthetic lethality effects of combining ULK1 depletion with p53 activation. Dual-luciferase reporter assay and ChIP-qPCR were performed to confirm that p53 directly mediates the transcription of GSDME and to identify the binding region of p53 in the promoter of GSDME. ULK1 knockout / overexpression cells were constructed to investigate the functional role of ULK1 both in vitro and in vivo. The mechanism of ULK1 depletion to activate GSMDE was mainly investigated by qPCR, western blot and ELISA., Results: By using high-throughput screening, we identified ULK1 as a synthetic lethal gene for the MDM2 inhibitor APG115. It was determined that deletion of ULK1 significantly increased the sensitivity, with cells undergoing typical pyroptosis. Mechanistically, p53 promote pyroptosis initiation by directly mediating GSDME transcription that induce basal-level pyroptosis. Moreover, ULK1 depletion reduces mitophagy, resulting in the accumulation of damaged mitochondria and subsequent increasing of reactive oxygen species (ROS). This in turn cleaves and activates GSDME via the NLRP3-Caspase inflammatory signaling axis. The molecular cascade makes ULK1 act as a crucial regulator of pyroptosis initiation mediated by p53 activation cells. Besides, mitophagy is enhanced in platinum-resistant tumors, and ULK1 depletion/p53 activation has a synergistic lethal effect on these tumors, inducing pyroptosis through GSDME directly., Conclusion: Our research demonstrates that ULK1 deficiency can synergize with MDM2 inhibitors to induce pyroptosis. p53 plays a direct role in activating GSDME transcription, while ULK1 deficiency triggers upregulation of the ROS-NLRP3 signaling pathway, leading to GSDME cleavage and activation. These findings underscore the pivotal role of p53 in determining pyroptosis and provide new avenues for the clinical application of p53 restoration therapies, as well as suggesting potential combination strategies., (© 2024. The Author(s).)

Cyanthillium cinereum, which belongs to the family of Asteraceae, is an annual or perennial herbaceous plant with significant medicinal uses for treating colds and fever. During September to November of 2020, C. cinereum showing symptoms of witches'-broom were found in economic forests distributed in Ding'an, Hainan Province of China, with 20% incidence. The symptoms of the plant were consistent with infections by 'Candidatus Phytoplasma' species. To identify the pathogen, five symptomatic and three asymptomatic C. cinereum samples were collected. Total DNAs were extracted using 0.10 g fresh leaf tissues of symptomatic and asymptomatic C. cinereum through a CTAB DNA extraction method according to Doyle and Doyle (1990). PCR amplification were performed employing the primer pairs of R16mF2/R16mR1 (Gundersen and Lee, 1996) and secAfor1/secArev3 (Hodgetts et al., 2008) specific for the conserved gene fragments of 16S rRNA and secA from phytoplasma. The PCR products were purified and sequenced through Biotechnology (Shanghai) Co., Ltd. (Guangzhou, China), and the obtained sequences were deposited in GenBank. The phytoplasmal 16S rRNA and secA gene fragments obtained in the study were all identical with the length of 1325 bp (GenBank accession: PP098738) and 741 bp (PP072217), respectively. The phytoplasma strain was described as CcWB-hnda. A BLAST search based on 16S rRNA genes indicated that CcWB-hnda strain was identical to phytoplasmas belonging to 16SrII group like peanut witches'-broom phytoplasma strain T48 (OR239773) and 'Ca. Phytoplasma aurantifolia' strain TB2022 (CP120449). Virtual RFLP profiles based on 16S rRNA gene fragments obtained by iPhyClassifier (Zhao et al., 2009) showed that CcWB-hnda strain was a member of 16SrII-A subgroup with 1.00 similarity coefficient to the reference phytoplasma strain (L33765). A BLAST search based on secA genes indicated that CcWB-hnda had 100% sequence identity with phytoplasmas belonging to 16SrII group such as 'Ca. Phytoplasma aurantifolia' isolate TB2022 (CP120449), Vigna unguiculata witches'-broom phytoplasma (OR661282) and Emilia sonchifolia witches'-broom phytoplasma (MW353710). Phylogenetic analysis based on 16S rRNA and secA genes by MEGA 7.0 employing Neighbor-Joining method with 1000 bootstrap value (Kumar et al., 2016; Felsenstein, 1985) demonstrated that CcWB-hnda was clustered into one clade with the phytoplasmas belonging to 16SrII group, with 98% and 100% bootstrap value respectively. To our knowledge, this is the first report of C. cinereum infected by phytoplasmas belonging to 16SrII-A subgroup in China. Identification of the vector insects of the pathogens is necessary in future, revealing the epidemiology of the related diseases. Phytoplasmas belonging to same 16Sr group or subgroup can infect different plants and spread through them in nature. The finding in this study will be beneficial to epidemic monitoring and early warning of C. cinereum witches'-broom disease and the related plant diseases caused by the phytoplasmas belonging to 16SrII group.

N-acetyl cysteine (NAC) is a versatile drug used in various conditions, but the limitations and toxicities are not clear. The acute toxicity and toxicological mechanisms of an intraperitoneal injection of NAC in normal mice were deciphered. The LD50 for male and female BALB/cByJNarl mice were 800 mg/kg and 933 mg/kg. The toxicological mechanisms of 800 mg/kg NAC (N800) were investigated. The serum biomarkers of hepatic and renal indices dramatically increased, followed by hepatic microvesicular steatosis, renal tubular injury and necrosis, and splenic red pulp atrophy and loss. Thus, N800 resulted in mouse mortality mainly due to acute liver, kidney, and spleen damages. The safe dose (275 mg/kg) of NAC (N275) increased hepatic antioxidant capacity by increasing glutathione levels and catalase activity. N275 elevated the hepatic gene expressions of lipid transporter, lipid synthesis, β-oxidation, and ketogenesis, suggesting a balance between lipid production and consumption, and finally, increased ATP production. In contrast, N800 increased hepatic oxidative stress by decreasing glutathione levels through suppressing Gclc, and reducing catalase activity. N800 decreased the hepatic gene expressions of lipid transporter, lipid synthesis, and interferred β-oxidation, leading to lipid accumulation and increasing Cyp2E1 expression, and finally, decreased ATP production. Therefore, NAC doses are limited for normal individuals, especially via intraperitoneal injection or similar means.

Background: In rhinoplasty, calcification around silicone implants is frequently observed in the tip dorsum (TD) area. Additionally, based on a review of various literature, it is presumed that calcification in silicone implants occurs due to both inflammatory chemical reactions and physical friction against the tissue. The calcification of nasal silicone implants not only results in the functional loss of the implants, but also leads to material deformation. However, there is a lack of research on calcification of nasal silicone implants in the current literature., Aim: To elucidate various clinical characteristics of calcification around nasal silicone implants, using histological and radiological analysis., Methods: This study analyzed data from 16 patients of calcified nasal implants, who underwent revision rhinoplasty for various reasons after undergoing augmentation rhinoplasty with silicone implants. The collected data included information on implant duration, implant types, location of calcification, presence of inflammatory reactions, and computed tomography (CT) scans., Results: The most common location of calcification, as visually analyzed, was in the TD area, accounting for 56%. Additionally, the analysis of CT scans revealed a trend of increasing Hounsfield Unit values for calcification with the duration of implantation, although this trend was not statistically significant ( P = 0.139)., Conclusion: Our study shows that reducing the frequency of calcification may be achievable by using softer silicone implants and by minimizing the damage to perioperative tissues., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study explored the assembly mechanisms and physicochemical dynamics of microbial communities within atmospheric bioaerosols, focusing on the influence of different aerial trajectories. Over two years, samples near Seoul were classified into 'North', 'Southwest', and 'Others' categories based on their aerial trajectories. Physicochemical analysis of the PM 2.5 particles revealed distinct ion compositions for each cluster, reflecting diverse environmental influences. Microbial community analysis revealed that shared dominant bacterial phyla were present in all clusters. However, distinct taxonomic profiles and biomarkers were also evident, such as coastal bacteria in the 'Southwest' cluster correlating with wind speed, and arid soil-originated bacteria in the 'North' cluster correlating with cations. These findings demonstrate that biomarkers in each cluster are representative of the distinct environments associated with their aerial trajectories. Notably, cluster 'Southwest' the highest microbial diversity and a strong alignment with the neutral community model, suggesting a large influence of passive dispersal from marine environments. Contrarily, 'North' and 'Others' were more influenced by niche-dependent factors. This study highlights the complex interplay between environmental factors and microbial dynamics in bioaerosols and provides important insights for environmental monitoring and public health risk assessment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Screening for osteoporosis is crucial for early detection and prevention, yet it faces challenges due to the low accuracy of calcaneal quantitative ultrasound (QUS) and limited access to dual-energy X-ray absorptiometry (DXA) scans. Recent advances in AI offer a promising solution through opportunistic screening using existing medical images. This study aims to utilize deep learning techniques to develop a model that analyzes chest X-ray (CXR) images for osteoporosis screening. This study included the AI model development stage and the clinical validation stage. In the AI model development stage, the combined dataset of 5122 paired CXR images and DXA reports from the patients aged 20 to 98 years at a medical center was collected. The images were enhanced and filtered for hardware retention such as pedicle screws, bone cement, artificial intervertebral discs or severe deformity in target level of T12 and L1. The dataset was then separated into training, validating, and testing datasets for model training and performance validation. In the clinical validation stage, we collected 440 paired CXR images and DXA reports from both the TCVGH and Joy Clinic, including 304 pared data from TCVGH and 136 paired data from Joy Clinic. The pre-clinical test yielded an area under the curve (AUC) of 0.940, while the clinical validation showed an AUC of 0.946. Pearson's correlation coefficient was 0.88. The model demonstrated an overall accuracy, sensitivity, and specificity of 89.0%, 88.7%, and 89.4%, respectively. This study proposes an AI model for opportunistic osteoporosis screening through CXR, demonstrating good performance and suggesting its potential for broad adoption in preliminary screening among high-risk populations.

Methods for regioselective N -trideuteromethylation of tautomeric polyaza heterocycles are highly sought-after. Disclosed herein is an N -trideuterated methylation reaction of imidazoles and pyrazoles with high regioselectivity and deuterium purity using easily available CF 3 SO 3 CD 3 as the -CD 3 source. This method enables the easy synthesis of important deuterium-labeled azoles, including dimetridazole- d 3 , ipronidazole- d 3 , hydroxy dimetridazole- d 3 , and ronidazole- d 3 .

Background: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial., Methods: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis., Results: Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029)., Conclusions: PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy., (© 2024. The Author(s).)

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder. The immune response plays a crucial role in AP progression. However, the impact of immune regulatory checkpoint PD-L1 on severe acute pancreatitis (SAP) remains uncertain. Hence, this study aimed to examine the influence of PD-L1 on SAP. We assessed PD-L1 expression in neutrophils and monocytes obtained from SAP patients. We induced SAP in C57BL/6J mice, PD-L1 gene-deficient mice, and PD-L1 humanized mice using intraperitoneal injections of cerulein plus lipopolysaccharide. Prior to the initial cerulein injection, a PD-L1 inhibitor was administered. Pancreatic tissues were collected for morphological and immunohistochemical evaluation, and serum levels of amylase, lipase, and cytokines were measured. Flow cytometry analysis was performed using peripheral blood cells. The expression of PD-L1 in neutrophils and monocytes was significantly higher in SAP patients compared to healthy individuals. Likewise, the expression of PD-L1 in inflammatory cells in the peripheral blood of SAP-induced C57BL/6J mice was notably higher than in the control group. In mice with PD-L1 deficiency, SAP model exhibited lower pancreatic pathology scores, amylase, lipase, and cytokine levels compared to wild-type mice. PD-L1 deletion resulted in reduced neutrophil apoptosis, leading to an earlier peak in neutrophil apoptosis. Furthermore, it decreased early monocyte apoptosis and diminished the peak of T lymphocyte apoptosis. Within the SAP model, administration of a PD-L1 inhibitor reduced pancreatic pathology scores, amylase, lipase, and cytokine levels in both C57BL/6J mice and PD-L1 humanized mice. These findings suggest that inhibiting PD-L1 expression can alleviate the severity of SAP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Lonicerae japonicae (L. japonicae) flos is a medical and food homology herb. This study investigated the phenolic acid and flavonoid contents in L. japonicae flos water extract solution (LJWES) and the preventive effects of LJWES against liver fibrogenesis via FL83B cells and rats. LJWES contains many polyphenols, such as chlorogenic acid, morin, and epicatechin. LJWES increased cell viability and decreased cytotoxicity in thioacetamide (TAA)-treated FL83B cells (75 mM) (p < .05). LJWES decreased (p < .05) gene expressions of Tnf-α, Tnfr1, Bax, and cytochrome c but upregulated Bcl-2 and Bcl-xl in TAA-treated cells; meanwhile, increased protein levels of P53, cleaved caspase 3, and cleaved caspase 9 in TAA treated cells were downregulated (p < .05) by LJWES supplementation. In vivo, results indicated that TAA treatment increased serum liver damage indices (alanine aminotransferase [ALT] and alkaline phosphatase [ALP]) and cytokines (interleukin-6 and transforming growth factor-β1) levels and impaired liver antioxidant capacities (increased thiobarbituric acid reactive substance value but decreased catalase/glutathione peroxidase activities) in rats (p < .05) while LJWES supplementation amended (p < .05) them. Liver fibrosis scores, collagen deposition, and alpha-smooth muscle actin deposition in TAA-treated rats were also decreased by LJWES supplementation (p < .05). To sum up, LJWES could be a potential hepatoprotective agent against liver fibrogenesis by enhancing antioxidant ability, downregulating inflammation in livers, and reducing apoptosis in hepatocytes., (© 2024 Wiley Periodicals LLC.)

Group theory is a powerful tool to explore fundamental symmetry constraints for the physical properties of crystal structures, e.g. it is well-known that only a few components of the elastic constants are independent due to the symmetry constraint. This work further applies group theory to derive constraint relationships for high-order elastic constants with respect to the orientation angle, where the constraint relationships are more explicit than the traditional tensor transformation law. These analytic symmetry constraints are adopted to explain the molecular dynamics simulation results, which disclose that the high-order elastic constants are highly anisotropic with an anisotropy percentage of up to 25% for the hexagonal boron nitride monolayer. The elastic constant is a basic quantity in the mechanics field, so its high anisotropy shall cause strong anisotropy for other mechanical properties. Based on the anisotropic high-order elastic constants, we demonstrate that Poisson's ratio is highly anisotropic for the hexagonal boron nitride at large strains. These findings provide fundamental insights into the symmetry dependence of high-order elastic constants and other mechanical properties.

Background: Brain metastasis (BM) in gastric cancer (GC) is underestimated, and human epidermal growth factor receptor 2 (HER2) overexpression is a durable poor prognostic factor. We explored the relationship between the two and made a survival analysis., Methods: HER2 expression and BM status were collected from GC patients who were diagnosed between December 2009 and May 2021. We collected GC patients diagnosed between 2010 and 2016 from the SEER database. The primary endpoint was survival from the diagnosis of BM. Multivariable logistic regression was used to determine potential risk factors of BM at diagnosis in SEER database. Survival analysis was performed using the Kaplan-Meier method., Result: There were 513 HER2-positive GC patients, including 16 (3.1%) with BM. Among 38 brain metastasis GC patients we collected, 16 (42.1%) patients were HER2 positive. We collected 34,199 GC patients from the SEER database and there were 260 (0.76%) patients with BM at diagnosis. GC patients that are male, white, of younger age, with primary lesions located in the proximal stomach or with distant lymph nodes, liver, bone, or lung metastasis are more likely to develop BM. The median overall survival time from diagnosis of BM was 12.73 months, and the survival time from brain metastasis of HER2-positive patients was numerically shorter, though the difference was not significant (5.30 months vs.16.13 months, P = 0.28.) CONCLUSION: The incidence of BM in patients with HER2-positive gastric cancer is 4.08 times higher than that in general patients. The median overall survival time from BM is shorter for HER2-positive patients., (© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

The QuEChERS (quick, easy, cheap, effective, rugged and safe) conditions were optimized for efficient determination of the U.S. Environmental Protection Agency (US EPA) and European Union (EU) priority polycyclic aromatic hydrocarbons (PAHs) for the categories of grains, tuber & starchy vegetables, soy beans and products, fish & seafood, and poultry & meat, including raw materials and their corresponding products. The PAHs were analyzed using ultrahigh-performance liquid chromatography with temperature-controlled fluorescence detection and gas chromatography with tandem mass spectrometry. The established conditions had good accuracy, repeatability, and precision. Environmental pollution and processing methods influence the level of PAHs in samples. The low molecular weight PAHs were present in all raw materials, and processing increased high and low molecular weight PAHs in the products. The excess cancer risk for consumption of PAHs in cooked samples was mostly acceptable; a small number of samples might be of slight concern in certain age groups.

Background: Hypertensive disorders of pregnancy (HDP) is the most common cause of indicated preterm delivery, but the impact of prenatal steroid exposure on the outcomes of preterm infants born to HDP mothers, who may be at risk for intrauterine hypoxia-ischemia, remains uncertain. The study objective is to evaluate the mortality and morbidities in HDP for very preterm infants (VPIs) exposed to different course of ANS., Methods: This is a prospective cohort study comprising infants with < 32 weeks gestation born to women with HDP only from 1 Jan. 2019 to 31 Dec. 2021 within 40 participating neonatal intensive care units (NICUs) in Sino-northern network. ANS courses included completed, partial, repeated, and no ANS. Univariate and multivariable analyses were performed on administration of ANS and short-term outcomes before discharge., Results: Among 1917 VPIs born to women with HDP only, 987(51.4%) received a complete course of ANS within 48 h to 7 days before birth, 560(29.2%) received partial ANS within 24 h before delivery, 100(5.2%) received repeat ANS and 270 (14.1%) did not receive any ANS. Compared to infants who received complete ANS, infants unexposed to ANS was associated with higher odds of death (AOR 1.85; 95%CI 1.10, 3.14), Severe Neurological Injury (SNI) or death (AOR 1.68; 95%CI 1.29,3.80) and NEC or death (AOR 1.78; 95%CI 1.55, 2.89), the repeated ANS group exhibits a significant negative correlation with the duration of oxygen therapy days (correlation coefficient - 18.3; 95%CI-39.2, -2.1). However, there were no significant differences observed between the full course and partial course groups in terms of outcomes. We can draw similar conclusions in the non-SGA group, while the differences are not significant in the SGA group. From KM curve, it showed that the repeated group had the highest survival rate, but the statistical analysis did not indicate a significant difference., Conclusions: Even partial courses of ANS administered within 24 h before delivery proved to be protective against death and other morbidities. The differences mentioned above are more pronounced in the non-SGA group. Repeat courses demonstrate a trend toward protection, but this still needs to be confirmed by larger samples., (© 2024. The Author(s).)

The Lamiaceae family is renowned for its terpenoid-based medicinal components, but Leonurus, which has traditional medicinal uses, stands out for its alkaloid-rich composition. Leonurine, the principal active compound found in Leonurus, has demonstrated promising effects in reducing blood lipids and treating strokes. However, the biosynthetic pathway of leonurine remains largely unexplored. Here, we present the chromosome-level genome sequence assemblies of Leonurus japonicus, known for its high leonurine production, and Leonurus sibiricus, characterized by very limited leonurine production. By integrating genomics, RNA sequencing, metabolomics, and enzyme activity assay data, we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase (ADC), uridine diphosphate glucosyltransferase (UGT), and serine carboxypeptidase-like (SCPL) acyltransferase enzymes that catalyze key reactions in this pathway. Further analyses revealed that the UGT-SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in L. japonicus, which contributed to the accumulation of leonurine specifically in L. japonicus. Collectively, our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus., (Copyright © 2023 The Author. Published by Elsevier Inc. All rights reserved.)

We study the property of equal-spin Andreev reflection (ESAR) in the ferromagnet/insulator/Ising superconductor junction where Ising spin-orbit coupling is taken into account in the insulator. It is found that the ESAR exhibits a regular oscillation with the insulating barrier, the amplitude and period of which can be effectively controlled by the chemical potentials. Compared to that in the ferromagnet/Ising superconductor junction, the ESAR is greatly increased due to the resonant mode, suggesting an enhanced spin-triplet pairing. As an application, the proposed junction may work as a switch to turn on and off the ESAR. Furthermore, the insulating barrier does not change the magnetoanisotropic period of ESAR because of the invariant symmetry of the system, however, the magnetoanisotropy is strengthened., (© 2023 IOP Publishing Ltd.)