Targeted degradation of KRAS protein in non-small cell lung cancer: Therapeutic strategies using liposomal PROTACs with enhanced cellular uptake and pharmacokinetic profiles.

The role of KRAS mutation in non-small cell lung cancer (NSCLC) initiation and progression is well-established. However, "undruggable" KRAS protein poses the research of small molecule inhibitors a significant challenge. Addressing this, proteolysis-targeting chimeras (PROTACs) have become a cutting-edge treatment method, emphasizing protein degradation. A modified ethanol injection method was employed in this study to formulate liposomes encapsulating PROTAC drug LC-2 (LC-2 LPs). Precise surface modifications using cell-penetrating peptide R8 yielded R8-LC-2 liposomes (R8-LC-2 LPs). Comprehensive cellular uptake and cytotoxicity studies unveiled that R8-LC-2 LPs depended on concentration and time, showcasing the superior performance of R8-LC-2 LPs compared to normal liposomes. In vivo pharmacokinetic profiles demonstrated the capacity of DSPE-PEG2000 to prolong the circulation time of LC-2, leading to higher plasma concentrations compared to free LC-2. In vivo antitumor efficacy research underscored the remarkable ability of R8-LC-2 LPs to effectively suppress tumor growth. This study contributed to the exploration of enhanced therapeutic strategies for NSCLC, specifically focusing on the development of liposomal PROTACs targeting the "undruggable" KRAS protein. The findings provide valuable insights into the potential of this innovative approach, offering prospects for improved drug delivery and heightened antitumor efficacy.

Center Variability in Acute Rejection and Biliary Complications After Pediatric Liver Transplantation.

Transplant center performance and practice variation for pediatric post-liver transplantation (LT) outcomes other than survival are understudied. This was a retrospective cohort study of pediatric LT recipients who received transplants between January 1, 2006, and May 31, 2017, using United Network for Organ Sharing (UNOS) data that were merged with the Pediatric Health Information System database. Center effects for the acute rejection rate at 1 year after LT (AR1) using UNOS coding and the biliary complication rate at 1 year after LT (BC1) using inpatient billing claims data were estimated by center-specific rescaled odds ratios that accounted for potential differences in recipient and donor characteristics. There were 2216 pediatric LT recipients at 24 freestanding children's hospitals in the United States during the study period. The median unadjusted center rate of AR1 was 36.92% (interquartile range [IQR], 22.36%-44.52%), whereas that of BC1 was 32.29% (IQR, 26.14%-40.44%). Accounting for recipient case mix and donor factors, 5/24 centers performed better than expected with regard to AR1, whereas 3/24 centers performed worse than expected. There was less heterogeneity across the center effects for BC1 than for AR1. There was no relationship observed between the center effects for AR1 or BC1 and center volume. Beyond recipient and allograft factors, differences in transplant center management are an important driver of center AR1 performance, and less so of BC1 performance. Further research is needed to identify the sources of variability so as to implement the most effective solutions to broadly enhance outcomes for pediatric LT recipients.

A novel approach on designing ultrahigh burnup metallic TWR fuels: Upsetting the current technological limits.

Abstract: The grand challenge of "net-zero carbon" emission calls for technological breakthroughs in energy production. The traveling wave reactor (TWR) is designed to provide economical and safe nuclear power and solve imminent problems, including limited uranium resources and radiotoxicity burdens from back-end fuel reprocessing/disposal. However, qualification of fuels and materials for TWR remains challenging and it sets an "end of the road" mark on the route of R&D of this technology. In this article, a novel approach is proposed to maneuver reactor operations and utilize high-temperature transients to mitigate the challenges raised by envisioned TWR service environment. Annular U-50Zr fuel and oxidation dispersion strengthened (ODS) steels are proposed to be used instead of the current U-10Zr and HT-9 ferritic/martensitic steels. In addition, irradiation-accelerated transport of Mn and Cr to the cladding surface to form a protective oxide layer as a self-repairing mechanism was discovered and is believed capable of mitigating long-term corrosion. This work represents an attempt to disruptively overcome current technological limits in the TWR fuels. Impact statement: After the Fukushima accident in 2011, the entire nuclear industry calls for a major technological breakthrough that addresses the following three fundamental issues: (1) Reducing spent nuclear fuel reprocessing demands, (2) reducing the probability of a severe accident, and (3) reducing the energy production cost per kilowatt-hour. An inherently safe and ultralong life fast neutron reactor fuel form can be such one stone that kills the three birds. In light of the recent development findings on U-50Zr fuels, we hereby propose a disruptive, conceptual metallic fuel design that can serve the following purposes at the same time: (1) Reaching ultrahigh burnup of above 40% FIMA, (2) possessing strong inherent safety features, and (3) extending current limits on fast neutron irradiation dose to be far beyond 200 dpa. We believe that this technology will be able to bring about revolutionary changes to the nuclear industry by significantly lowering the operational costs as well as improving the reactor system safety to a large extent. Supplementary information: The online version contains supplementary material available at 10.1557/s43577-022-00420-4.

Connexin 43 participates in atrial electrical remodelling through colocalization with calcium channels in atrial myocytes.

Atrial fibrillation (AF) is associated with atrial conduction disturbances caused by electrical and/or structural remodelling. In the present study, we hypothesized that connexin might interact with the calcium channel through forming a protein complex and, then, participates in the pathogenesis of AF. Western blot and whole-cell patch clamp showed that protein levels of Cav1.2 and connexin 43 (Cx43) and basal ICa,L were decreased in AF subjects compared to sinus rhythm (SR) controls. In cultured atrium-derived myocytes (HL-1 cells), knocking-down of Cx43 or incubation with 30 mmol/L glycyrrhetinic acid significantly inhibited protein levels of Cav1.2 and Cav3.1 and the current density of ICa,L and ICa,T . Incubation with nifedipine or mibefradil decreased the protein level of Cx43 in HL-1 cells. Moreover, Cx43 was colocalized with Cav1.2 and Cav3.1 in atrial myocytes. Therefore, Cx43 might regulate the ICa,L and ICa,T through colocalization with calcium channel subunits in atrial myocytes, representing a potential pathogenic mechanism in AF.

Activation of PKCα participates in the reduction of Ikur in atrial myocytes induced by tumour necrosis factor-α.

The atrial-specific ultra-rapid delayed rectifier K+ current (Ikur) plays an important role in the progression of atrial fibrillation (AF). Because inflammation is known to lead to the onset of AF, we aimed to investigate whether tumour necrosis factor-α (TNF-α) played a role in regulating Ikur and the potential signalling pathways involved. Whole-cell patch-clamp and biochemical assays were used to study the regulation and expression of Ikur in myocytes and in tissues from left atrial appendages (LAAs) obtained from patients with sinus rhythm (SR) or AF, as well as in rat cardiomyocytes (H9c2 cells) and mouse atrial myocytes (HL-1 cells). Ikur current density was markedly reduced in atrial myocytes from AF patients compared with SR controls. Reduction of Kv1.5 protein levels was accompanied by increased expression of TNF-α and protein kinase C (PKC)α activation in AF patients. Treatment with TNF-α dose-dependently reduced Ikur and protein expression of Kv1.5 but not Kv3.1b in H9c2 cells and HL-1 cells. TNF-α also increased activity of PKCα. Specific PKCα inhibitor Gö6976 alleviated the reduction in Ikur induced by TNF-α, but not the reduction in Kv1.5 protein. TNF-α was involved in the electrical remodelling associated with AF, probably by depressing Ikur in atrial myocytes via activation of PKCα.

Ratiometric electrochemical sensing based on Mo2C for detection of acetaminophen.

In this work, MoO2 nanoparticles were synthesized and annealed to form Mo2C nanoparticles. This is the first report of a ratiometric electrochemical sensor (R-ECS) for the detection of acetaminophen (AP), in which Mo2C is used as the sensing agent and ferrocene (FC) is used as an internal reference. FC (100 µM) is added directly to the electrolyte solution for convenient operation. The synthesized materials were fully characterized with respect to composition, morphology and electrochemical performance. The oxidation peak potentials of FC (0.196 V) and AP (0.364 V) can be completely separated by the Mo2C modified glassy carbon electrode, and their ratiometric signals are used for the quantification of AP. It was found that the oxidation peak currents of AP at separated potentials on Mo2C/GCE are linear with concentration in the range of 0.5-600 µM, and the detection limit is 0.029 µM (S/N = 3). Mo2C/GCE exhibited decent repeatability, reproducibility, stability, and selectivity. The sensor was then applied to measure AP in tap water and river water.

Targeted and nontargeted screening and identification of 50 antihypertensive adulterants in dietary supplements and herbal medicines using quadrupole-orbitrap high resolution mass spectrometry with compound database.

In the present work, a novel database of drug compounds and a rapid screening method based on ultra-high performance liquid chromatography coupled to high resolution orbitrap mass spectrometry were developed and applied in the screening and identification of targeted and nontargeted antihypertensive adulterants in dietary supplements and herbal medicines. The established screening database includes retention time, exact mass, fragments, isotopic pattern, and MS2 spectra library of the target compounds and thus provides automated search and identification of the targets with a single injection. The nontargeted compounds in the samples are identified through the full MS scan and MS2 data by using the Chemspider database and the data analysis in XCalibur, MassFrontier and TraceFinder software. In addition, this method possesses excellent quantitative capacity. The novel approach was applied to 65 batches of samples that are claimed as "all-natural" products having the antihypertensive function, among which nine batches were found to be positive. Multiple targeted and nontargeted antihypertensive adulterants were detected at levels ranging from 2.8 to 27.9 mg/g. The novel database and screening method demonstrated herein will be promising and powerful tools for rapid screening of antihypertensive adulterants in dietary supplements and herbal medicines.

A Zn Metal-Organic Framework with High Stability and Sorption Selectivity for CO2.

A three-dimensional porous Zn metal-organic framework (UPC-12) with high thermal and chemical stability was isolated in high yield and purity from a hydrothermal reaction. UPC-12 exhibits high selectivity for CO2 due to the formation of hydrogen bonds between CO2 molecules and the -COOH groups exposed inside the channels and the effective π-π interactions between CO2 molecules and the pillared bipyridine moieties of the MOF. The adsorption-desorption process was studied, for the first time, by both (13)C CP-TOSS NMR spectroscopy and in situ DRIFTS.

Porous zirconium metal-organic framework constructed from 2D → 3D interpenetration based on a 3,6-connected kgd net.

A new porous zirconium metal-organic framework (Zr MOF), Zr6(µ3-O)4(µ3-OH)4(OH)6(H2O)6(BTB)2·6DMF·H2O (1; H3BTB = 5'-(4-carboxyphenyl)[1,1':3',1″-terphenyl]-4,4″-dicarboxylic acid), based on Zr6 clusters and tricarboxylate ligands has been constructed and characterized. The Zr6 clusters were linked by BTB ligands to generate a 2D network of kgd topology. The interpenetrations among the 2D networks gave rise to a 3D porous framework, which represents the first Zr MOF constructed from 2D → 3D interpenetration. The gas uptake and catalytic properties for 1 have also been studied.

The Effects of Irradiation on the Improvement in Oxidation Behavior of MX-ODS Steel in Liquid Pb.

Lead-cooled fast reactors exhibit strong inherent safety performance and good economic features, while material degradation due to corrosion and irradiation is still challenging. Oxide dispersion-strengthened steels are one of the promising candidates for fuel cladding materials. The effects of both irradiation and corrosion on ODS steel need to be further studied. In this work, MX-ODS steel was irradiated by Fe ions at 500 °C up to 46 dpa. Later, the as-received specimen and the irradiated specimen were used to conduct corrosion tests in oxygen-saturated Pb at 550 °C for 1 h. In the as-received specimen, discontinuous oxides penetrated by Pb and Pb in contact with steel matrix were observed, demonstrating unsatisfactory corrosion resistance of the material. However, in the irradiated specimen after corrosion experiment, a protective oxide layer formed and prevented Pb attack. The oxidation behavior differences between the two specimens can be attributed to the defects produced by irradiation and the structural discrepancy in oxides caused by the formation process. A possible mechanism of irradiation on the corrosion is discussed. In the as-received specimen, Fe atoms loss led to voids in the oxides, and lead penetrated the oxides through these voids. In the irradiated specimen, defects left by previous irradiation helped to form a more uniform oxide layer. The adhesive outer magnetite oxide and the Fe ions generated from where grain boundary oxidation developed retarded the presence of voids and made the oxide layer protective.

Ruthenium-Arene-ß-Carboline Complexes as Potent Inhibitors of Cyclin-Dependent Kinase 1: Synthesis, Characterization and Anticancer Mechanism Studies.

A series of Ru(II)-arene complexes (1-6) of the general formula [(η(6)-arene)Ru(L)Cl]PF6 (arene=benzene or p-cymene; L=bidentate ß-carboline derivative, an indole alkaloid with potential cyclin-dependent kinases (CDKs) inhibitory activities) is reported. All the complexes were fully characterized by classical analytical methods, and three were characterized by X-ray crystallography. Hydrolytic studies show that ß-carboline ligands play a vital role in their aqueous behaviour. These complexes are highly active in vitro, with the most active complex 6 displaying a 3- to 12-fold higher anticancer activity than cisplatin against several cancer cell lines. Interestingly, the complexes are able to overcome cross-resistance to cisplatin, and show much lower cytotoxicity against normal cells. Complexes 1-6 may directly target CDK1, because they can block cells in the G2M phase, down-regulate the expression of CDK1 and cyclin B1, and inhibit CDK1/cyclin B in vitro. Further mechanism studies show that the complexes can effectively induce apoptosis through mitochondrial-related pathways and intracellular reactive oxygen species (ROS) elevation.

Physiological responses and transcriptome analysis of soybean under gradual water deficit.

Soybean is an important food and oil crop widely cultivated globally. However, water deficit can seriously affect the yield and quality of soybeans. In order to ensure the stability and increase of soybean yield and improve agricultural water use efficiency (WUE), research on improving drought tolerance and the efficiency of water utilization of soybeans under drought stress has become particularly important. This study utilized the drought-tolerant variety Heinong 44 (HN44) and the drought-sensitive variety Suinong 14 (SN14) to analyze physiological responses and transcriptome changes during the gradual water deficit at the early seed-filling stage. The results indicated that under drought conditions, HN44 had smaller stomata, higher stomatal density, and lower stomatal conductance (Gs) and transpiration rate as compared to SN14. Additionally, HN44 had a higher abscisic acid (ABA) content and faster changes in stomatal morphology and Gs to maintain a dynamic balance between net photosynthetic rate (Pn) and Gs. Additionally, drought-tolerant variety HN44 had high instantaneous WUE under water deficit. Further, HN44 retained a high level of superoxide dismutase (SOD) activity and proline content, mitigating malondialdehyde (MDA) accumulation and drought-induced damage. Comprehensive analysis of transcriptome data revealed that HN44 had fewer differentially expressed genes (DEGs) under light drought stress, reacting insensitivity to water deficit. At the initial stage of drought stress, both varieties had a large number of upregulated DEGs to cope with the drought stress. Under severe drought stress, HN44 had fewer downregulated genes enriched in the photosynthesis pathway than SN14, while it had more upregulated genes enriched in the ABA-mediated signaling and glutathione metabolism pathways than SN14. During gradual water deficit, HN44 demonstrated better drought-tolerant physiological characteristics and water use efficiency than SN14 through key DEGs such as GmbZIP4, LOC100810474, and LOC100819313 in the major pathways. Key transcription factors were screened and identified, providing further clarity on the molecular regulatory pathways responsible for the physiological differences in drought tolerance among these varieties. This study deepened the understanding of the drought resistance mechanisms in soybeans, providing valuable references for drought-resistant soybean breeding.

Induction Immunosuppression Does Not Worsen Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Prior studies are inconsistent regarding the impact of antibody induction therapy on outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). METHODS: Adults transplanted with HCC exception priority were identified from February 27, 2002, to March 31, 2019, using the United Network for Organ Sharing database. Time-to-event analyses evaluated the association of antibody induction therapy (none, nondepleting induction [NDI], depleting induction [DI]) with overall post-LT patient survival and HCC recurrence. Separate multivariable models adjusted for tumor characteristics on either last exception or on explant. The interaction of induction and maintenance regimen at LT discharge was investigated. RESULTS: Among 22 535 LTs for HCC, 17 688 (78.48%) received no antibody induction, 2984 (13.24%) NDI, and 1863 (8.27%) DI. Minimal differences in patient and tumor characteristics were noted between induction groups, and there was significant center variability in practices. NDI was associated with improved survival, particularly when combined with a calcineurin inhibitor (CNI) and antimetabolite (hazard ratio [HR] 0.73 versus no induction plus 3-drug therapy in the last exception model [ P < 0.001]; HR 0.64 in the explant model [ P = 0.011]). The combination of DI with CNI alone was also protective (HR 0.43; P = 0.003). Neither NDI nor DI was associated with tumor recurrence (all P > 0.1). However, increased HCC recurrence was observed with no induction plus CNI monotherapy (HR 1.47, P = 0.019; versus no induction plus 3-drug therapy). CONCLUSIONS: In conclusion, induction immunosuppression was not associated with worse post-LT outcomes in patients transplanted with HCC exception priority. An improvement in survival was possibly observed with NDI.

Structure-Interaction Relationship of Polymyxins with Lung Surfactant.

Multidrug-resistant Gram-negative bacteria present an urgent and formidable threat to the global public health. Polymyxins have emerged as a last-resort therapy against these 'superbugs'; however, their efficacy against pulmonary infection is poor. In this study, we integrated chemical biology and molecular dynamics simulations to examine how the alveolar lung surfactant significantly reduces polymyxin antibacterial activity. We discovered that lung surfactant is a phospholipid-based permeability barrier against polymyxins, compromising their efficacy against target bacteria. Next, we unraveled the structure-interaction relationship between polymyxins and lung surfactant, elucidating the thermodynamics that govern the penetration of polymyxins through this critical surfactant layer. Moreover, we developed a novel analog, FADDI-235, which exhibited potent activity against Gram-negative bacteria, both in the presence and absence of lung surfactant. These findings shed new light on the sequestration mechanism of lung surfactant on polymyxins and importantly pave the way for the rational design of new-generation lipopeptide antibiotics to effectively treat Gram-negative bacterial pneumonia.

Involvement of plasminogen activator inhibitor-1 in p300/p53-mediated age-related atrial fibrosis.

Plasminogen activator inhibitor-1 (PAI-1), a key regulator of the fibrinolytic system, is also intimately involved in the fibrosis. Although PAI-1 may be involved in the occurrence of atrial fibrillation (AF) and thrombosis in the elderly, but whether it participated in aging-related atrial fibrosis and the detailed mechanism is still unclear. We compared the transcriptomics data of young (passage 4) versus senescent (passage 14) human atrial fibroblasts and found that PAI-1 was closely related to aging-related fibrosis. Aged mice and senescent human and mouse atrial fibroblasts underwent electrophysiological and biochemical studies. We found that p300, p53, and PAI-1 protein expressions were increased in the atrial tissue of aged mice and senescent human and mouse atrial fibroblasts. Curcumin or C646 (p300 inhibitor), or p300 knockdown inhibited the expression of PAI-1 contributing to reduced atrial fibroblasts senescence, atrial fibrosis, and the AF inducibility. Furthermore, p53 knockdown decreased the protein expression of PAI-1 and p21 in senescent human and mouse atrial fibroblasts. Our results suggest that p300/p53/PAI-1 signaling pathway participates in the mechanism of atrial fibrosis induced by aging, which provides new sights into the treatment of elderly AF.

Synthesis of 3-O-Acetyl-11-keto-ß-boswellic Acid (AKBA)-Derived Amides and Their Mitochondria-Targeted Antitumor Activities.

In this study, we synthesized a series of amide and mitochondria-targeted derivatives with 3-O-acetyl-11-keto-ß-boswellic acid (AKBA) as the parent structure and an ethylenediamine moiety as the link chain. Compound 5e, a mitochondrial-targeting potential derivative, showed significantly stronger antitumor activity than that of AKBA, and it could induce vacuolization of A549 cells and stimulate the production of reactive oxygen species (ROS) in a time- and concentration-dependent manner. The antioxidant N-acetylcysteine (NAC) could inhibit the ROS level but could not suppress vacuolization and cell death induced by 5e. Further studies demonstrated that 5e caused abnormal opening of mitochondrial permeability transition pore (MPTP) and a decrease of mitochondrial membrane potential; additionally, it caused cell cycle arrest in G0/G1 but did not induce apoptosis. 5e represented a compound with improved antiproliferative effects for cancer therapy working through new mechanisms.

Clinical Utility in Adopting Race-free Kidney Donor Risk Index.

Recent events of racial injustice prompted us to study potential impact of removing race from kidney donor risk index (KDRI) calculator. Methods: We used Scientific Registry for Transplant Recipients data to analyze outcomes of 66 987 deceased-donor kidney transplants performed in the United States between 2010 and 2016. Graft failure (GF) was defined as death or return to dialysis or requiring repeat transplant. We compared original KDRI and a race-free KDRI (Black donor coefficient zeroed out in the KDRI formula) with respect to recategorization of perceived GF risk (based on KDPI categories: ≤20, 21-34, 35-85, ≥86)' risk discrimination (using the C statistic) and predictive accuracy (using Brier score), and GF risk prediction (using Cox regression on time-to-GF). We used logistic regression to study the impact of donor race on discard probability. Results: There were 10 949 (16.3% of recipients) GF, and 1893 (17% of GFs) were among recipients of kidneys from Black donors. The use of race-free KDRI resulted in reclassification of 49% of kidneys from Black donors into lower GF risk categories. The impact on GF risk discrimination was minimal, with a relative decrease in C statistic of 0.16% and a change in GF predictive accuracy of 0.07%. For a given recipient/donor combination, transplants from Black (compared with non-Black) donors are estimated to decrease predicted graft survival at 1-y by 0.3%-3%, and 5-y by 1%-6%. Kidneys from Black donors are significantly more likely to be discarded (odds ratio adjusted for KDRI except race = 1.24). We estimate that an equal discard probability for Black and non-Black donors would yield 70 additional kidney transplants annually from Black donors. Conclusions: Use of race-free KDRI did not impact GF risk discrimination or predictive accuracy and may lower discard of kidneys from Black donors. We recommend use of race-free KDRI calculator acknowledging the possibility of miscalculation of GF risk in small proportion of kidneys from Black donors.

[Determination of trace genotoxic impurities in nifedipine by ultra high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry].

A method based on ultra high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry (UHPLC-Orbitrap HRMS) was established for the determination of genotoxic impurities 2, 6, and 12 in nifedipine. After extraction with methanol, the sample was injected into the UHPLC-Orbitrap HRMS system for analysis. An ACE EXCELTM 3 C18-AR column (150 mm×4.6 mm, 3 µm) was used for chromatographic separation. The mobile phase was methanol-0.1% formic acid aqueous solution (65∶35, v/v). The flow rate was 0.6 mL/min, while the column temperature and autosampler temperature were set as 35 ℃ and 8 ℃, respectively. The divert valve switching technique was used to protect the mass spectrometer. The six-way valve was set to divert the eluent of 7.5-11.6 min to waste and the rest of the eluent into the mass spectrometer. The Orbitrap mass spectrometer was coupled with the UHPLC system by an electrospray ion (ESI) source. The sheath gas and auxiliary gas flow rates were 60 and 20 arb (arbitrary units), respectively. The spray voltage was 3.5 kV, while the capillary temperature and auxiliary gas heater temperature were set as 350 ℃ and 400 ℃, respectively. The positive ion parallel reaction monitoring (PRM) scanning mode was adopted, and the mass spectral resolution was set to 35000 FWHM. The accurate masses of the [M+H]+ precursor ions of impurities 2, 6, and 12 were m/z 347.1230, 361.1026, and 347.1230, respectively. The accurate masses of the extracted [M+H]+ fragment ions of impurities 2, 6, and 12 were m/z 315.0968, 298.1069, and 315.0968, respectively. The normalized collision energies (NCEs) were optimized to 10%, 42%, and 10% for impurities 2, 6, and 12, respectively. The external standard method was utilized for quantitative analysis. The established method was validated in detail by investigating the specificity, linear range, limit of detection (LOD), limit of quantification (LOQ), recovery, precision, and stability. This method had good specificity, and the solvent did not interfere with the determination of impurities. The peak areas of impurities 2, 6, and 12 as well as their concentrations showed good linear relationships in the ranges of 0.2-100 ng/mL, with all correlation coefficients (r)≥0.9998. The recoveries of impurities 2, 6, and 12 at three levels (low, medium, and high) were in the range of 96.9%-105.0%, while the RSDs were between 1.21% and 5.12%. The LODs were 0.05 ng/mL and the LOQs were 0.2 ng/mL for all three impurities. This analytical method was used to determine impurities 2, 6, and 12 in three batches of nifedipine samples. Impurity 6 was not detected in the three batches, but impurities 2 and 12 were detected in all the three samples, and the detection amount was within the limit. The developed method is sensitive, fast, accurate, and easy to operate. It can provide a reference for the quality control of nifedipine by pharmaceutical companies and extend strong technical support for the supervision by drug regulatory authorities.

Mechanical Performance Study of Beam-Column Connection with U-Shaped Steel Damper.

The article proposes the use of a semi-rigid energy-dissipation connection combined with a U-shaped metal damper to avoid brittle failure of rigid steel beam-column connections under seismic loading. The U-shaped metal damper connects the H-section column and the H-section beam to form a new energy-dissipation connection as an energy-dissipation member. Compared with the existing research, this connection has a stable energy-dissipation performance and great ductility. To clarify the mechanism of energy dissipation, mechanical models under two U-shaped damping deformation modes are established. The calculation formulas for the yield load and stiffness are derived for the corresponding deformation mode using the unit load method. Taking the T-shaped beam-column connection and the application of U-shaped steel damper in the beam-column connection as an example, the mechanical model of the connection is established and the calculation formulas for the yield load and stiffness are derived. At the same time, the connection is subjected to a quasi-static test under cyclic loading. The results show that the hysteretic curve of the test is complete and that the skeleton curve is accurate compared to the theory. The error range of the initial stiffness and yield load obtained by the test and the theoretical formula is kept within 20%, indicating that the theoretical formula is reasonable and feasible. In addition, the correctness of the finite element model is verified by establishing a finite element model and comparing it with the test. The mechanical responses of purely rigid connections and rigid semi-rigid composite connections are compared and analyzed using a multi-story and multi-span plane frame as an example. The results show that the model with semi-rigid connections, compared to the model with rigid connections, avoids the gradual loss of bearing capacity caused by the failure of the connection area of the second floor of the main structure and improves the seismic performance of the main structure.

Two new sesquiterpenoid lactone derivatives from Lindera aggregata.

Two new sesquiterpenoid lactone derivatives, linderin A (1) and linderin B (2) comprising a sesquiterpenoid lactone and a methyl geranylhomogentisate moiety together with six known compounds were isolated from the roots of Lindera aggregata. Their chemical structures were elucidated using extensive spectroscopic analysis including 1 D, 2 D NMR, and HR-ESI-MS data and compared with previously reported data. The absolute configurations of 1 and 2 were assigned based on the electronic circular dichroism calculation. Compound 2 showed moderate anticoagulant activity.