跳-扩散模型下期权定价方法及参数校准

该文对跳-扩散模型下期权定价方法及参数校准问题进行研究.首先,推导出了跳-扩散模型在均值修正等价鞅测度下的风险中性特征函数,利用COS方法对跳-扩散模型进行期权定价,分析了COS方法的定价误差,并通过数值实验验证了COS定价方法的有效性;然后,采用相对熵正则化方法对跳-扩散模型进行参数校准,通过数值模拟实验验证了校准方法的准确性和可靠性;最后,利用S&P500市场数据对模型参数进行校准.结果表明:不同到期日期权数据校准结果有很大不同,Merton跳-扩散模型比Black-Scholes模型能更好的模拟市场数据.

Harmonic scalpel versus traditional scissors in laparoscopic partial nephrectomy:A propensity score-based analysis

Objective:The present study aims to compare the clinical efficacy of laparoscopic partial nephrectomy using a harmonic scalpel versus traditional scissor.Methods:A retrospective review was conducted in patients with localized renal tumors and scheduled for laparoscopic partial nephrectomy from January 2015 to December 2019.Eventually,225 patients joined this retrospective study.Patients were divided into the harmonic scalpel group or scissor group based on the method used,with 71 cases and 154 cases respectively.Propensity score matching(1:1)was performed to adjust for potential baseline confounders,and each group had 57 cases.Patient characteristics,perioperative clinical results,complications,and oncological results were compared between the two groups.Results:After matching,patient characteristics were not significantly different between the two groups.The scissor group was associated with a significantly shorter operative time(105 min vs.130 min,p<0.001),shorter warm ischemia time(19.35 min vs.22.07 min,p?0.005).However,the harmonic scalpel group was associated with significantly less estimated blood loss(20 mL vs.30 mL,p?0.013)and shorter length of stay(8 d vs.10 d,p?0.040).There was no significantly difference in indwelling time of drainage tube,perioperative complication,oncological outcomes or recurrence rates.Conclusions:The harmonic scalpel is used safely and effectively in laparoscopic partial nephrectomy,and has benefits in intraoperative blood loss and length of stay.

Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators(e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges,including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result,the design of new epigenetic modulators(e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging(Hy T) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review,we aim to provide an in-depth illustration of new degrading strategies(2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Photo-controlled release of paclitaxel and model drugs from RNA pyramids

Stimuli-resp on sive release of drugs from a nano carrier in spatial-,temporal-,and dosage-controlled fashi ons is of great interest in the pharmaceutical industry.Paclitaxel is one of the most effective and popular chemotherapeutic drugs against a number of cancers such as metastatic or non metastatic breast can cer,non-small cell lung can cer,refractory ovaria n cancer,AIDS-related Kaposi's sarcoma,and head and neck can cers.Here,by taki ng the adva ntage of RNA nanotechno logy in biomedical and material scie nee,we developed a three-dime nsional pyramid-shaped RNA nanocage for a photocontrolled release of cargo,using paclitaxel as a model drug.The light-triggered release of paclitaxel or fluorophore Cy5 was achieved by incorporation of photocleavable spacers into the RNA nanoparticles.Upon irradiation with ultraviolet light,cargos were rapidly released(within 5 min).In vitro treatment of breast can cer cells with the RNA nano particles harbori ng photocleavable paclitaxel showed higher cytotoxicity as compared to RNA nanoparticles without the photocleavable spacer.The methodology provides proof of con cept for the applicati on of the light-triggered con trolled release of drugs from RNA nano cages.

Ligand-based substituent-anchoring design of selective receptor-interacting protein kinase 1 necroptosis inhibitors for ulcerative colitis therapy

Receptor-interacting protein(RIP)kinase 1 is involved in immune-mediated inflammatory diseases including ulcerative colitis(UC)by regulating necroptosis and inflammation.Our group previously identified TAK-632(5)as an effective necroptosis inhibitor by dual-targeting RIP1 and RIP3.In this study,using ligand-based substituent-anchoring design strategy,we focused on the benzothiazole ring to obtain a series of TAK-632 analogues showing significantly improving on the anti-necroptosis activity and RIP1 selectivity over RIP3.Among them,a conformational constrained fluorine-substituted derivative(25)exhibited 333-fold selectivity for RIP1(K_(d)= 15 nmol/L)than RIP3(K_(d)>5000 nmol/L).This compound showed highly potent activity against cell necroptosis(EC_(50)=8 nmol/L)and systemic inflammatory response syndrome(SIRS)induced by TNF-α in vivo.Especially,it was able to exhibit remarkable anti-inflammatory treatment efficacy in a DSS-induced mouse model of UC.Taken together,the highly potent,selective,orally active anti-necroptosis inhibitor represents promising candidate for clinical treatment of UC.

N-Type Mg_(3)Sb_(2-x)Bi_(x) Alloys as Promising Thermoelectric Materials

N-type Mg_(3)Sb_(2-x)Bi_(x) alloys have been extensively studied in recent years due to their significantly enhanced thermoelectric figure of merit(zT),thus promoting them as potential candidates for waste heat recovery and cooling applications.In this review,the effects resulting from alloying Mg_(3)Bi_(2) with Mg_(3)Sb_(2),including narrowed bandgap,decreased effective mass,and increased carrier mobility,are summarized.Subsequently,defect-controlled electrical properties in n-type Mg_(3)Sb_(2-x)Bi_(x) are revealed.On one hand,manipulation of intrinsic and extrinsic defects can achieve optimal carrier concentration.On the other hand,Mg vacancies dominate carrier-scattering mechanisms(ionized impurity scattering and grain boundary scattering).Both aspects are discussed for Mg_(3)Sb_(2-x)Bi_(x) thermoelectric materials.Finally,we review the present status of,and future outlook for,these materials in power generation and cooling applications.

Construction of RNA nanotubes

Nanotubes are miniature materials with significant potential applications in nanotechnological, medical, biological and material sciences. The quest for manufacturing methods of nano-mechanical modules is in progress. For example, the application of carbon nanotubes has been extensively investigated due to the precise width control, but the precise length control remains challenging. Here we report two approaches for the one-pot self-assembly of RNA nanotubes. For the first approach, six RNA strands were used to assemble the nanotube by forming a 11 nm long hollow channel with the inner diameter of 1.7 nm and the outside diameter of 6.3 nm. For the second approach, six RNA strands were designed to hybridize with their neighboring strands by complementary base pairing and formed a nanotube with a six-helix hollow channel similar to the nanotube assembled by the first approach. The fabricated RNA nanotubes were characterized by gel electrophoresis and atomic force microscopy (AFM), confirming the formation of nanotube-shaped RNA nanostructures. Cholesterol molecules were introduced into RNA nanotubes to facilitate their incorporation into lipid bilayer. Incubation of RNA nanotube complex with the free-standing lipid bilayer membrane under applied voltage led to discrete current signatures. Addition of peptides into the sensing chamber revealed discrete steps of current blockage. Polyarginine peptides with different lengths can be detected by current signatures, suggesting that the RNA-cholesterol complex holds the promise of achieving single molecule sensing of peptides.

3D RNA nanocage for encapsulation and shielding of hydrophobic biomolecules to improve the in vivo biodistribution

Ribonucleic acid(RNA)nanotechnology platforms have the potential of harboring therapeutics for in vivo delivery in disease treatment.However,the nonspecific interaction between the harbored hydrophobic drugs and cells or other components before reaching the diseased site has been an obstacle in drug delivery.Here we report an encapsulation strategy to prevent such nonspecific hydrophobic interactions in vitro and in vivo based on a self-assembled three-dimensional(3D)RNA nanocage.By placing an RNA three-way junction(3WJ)in the cavity of the nanocage,the conjugated hydrophobic molecules were specifically positioned within the nanocage,preventing their exposure to the biological environment.The assembly of the nanocages was characterized by native polyacrylamide gel electrophoresis(PAGE),atomic force microscopy(AFM),and cryogenic electron microscopy(cryo-EM)imaging.The stealth effect of the nanocage for hydrophobic molecules in vitro was evaluated by gel electrophoresis,flow cytometry,and confocal microscopy.The in vivo sheathing effect of the nanocage for hydrophobic molecules was assessed by biodistribution profiling in mice.The RNA nanocages with hydrophobic biomolecules underwent faster clearance in liver and spleen in comparison to their counterparts.Therefore,this encapsulation strategy holds promise for in vivo delivery of hydrophobic drugs for disease treatment.

Radial electromagnetic type unbalance vibration self-recovery regulation system for high-end grinding machine spindles

Modern rotating machines,which are represented by high-end grinding machines,have developed toward high precision,intelligence,and high durability in recent years.As the core components of grinding machine spindles,grinding wheels greatly affect the vibration level during operation.The unbalance vibration self-recovery regulation(UVSRR)system is proposed to suppress the vibration of grinding wheels during workpiece processing,eliminating or minimizing the imbalance.First,technical principles and the system composition are introduced.Second,the balancing actuator in the UVSRR system is analyzed in detail.The advanced nature of the improved structure is presented through structure introduction and advantage analysis.The performance of the balancing actuator is mutually verified by the theoretical calculation of torque and software simulation.Results show that the self-locking torque satisfies the actual demand,and the driving torque is increased by 1.73 times compared with the traditional structure.Finally,the engineering application value of the UVSRR system is verified by laboratory performance comparison and actual factory application.The balancing speed and effect of the UVSRR system are better than those of an international mainstream product and,the quality of the workpieces machined in the factory improved by 40%.