Clinical efficacy of apatinib as a second-line treatment for advanced pancreatic cancer in a Chinese tertiary cancer health facility

Purpose: To study the effectiveness and safety of apatinib as second-line treatment for advanced pancreatic cancer (APC) in a Chinese tertiary cancer hospital. Methods: Two groups of APC patients who received treatment with single-agent or two-drug combination of gemcitabine-based first-line therapy (50 per group) in The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing were assessed. The study group received apatinib at or above the second line treatment, while the control group was treated with second-line chemotherapy, which was different from first-line single-drug chemotherapy. Patients received treatments until there was improvement in their conditions, or until adverse reactions became intolerable. Complete remission (CR), partial remission (PR), disease stabilization (SD), disease progression (PD), incidence of adverse reactions, and progression-free survival (PFS) of the patients were recorded. Results: The number of PR cases in APC patients who received apatinib as second-line therapy, and the number of PD patients were higher than the corresponding populations in the control group (p < 0.05). Treatment effectiveness was significantly higher in study group patients than in control subjects (p < 0.05). However, the incidence of adverse reactions was lower in the study group than in control group. Median PFS in the study group (5 months) was significantly higher than that of the control group (4.1 months, p < 0.05). Conclusion: The clinical efficacy of apatinib as second-line treatment for advanced pancreatic cancer is higher than that of the single drug. Apatinib is associated with low incidence of adverse reactions which prolongs PFS. Thus, apatinib has potentials for the clinical management of pancreatic cancer

Protective effect of aprepitant against chemotherapy induced nausea and vomiting in postoperative chemotherapy for gastric cancer

Purpose: To investigate the clinical efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by schemotherapy after gastric cancer surgery, and associated factors, as well as adverse reactions to the drug. Methods: A total of 100 postoperative gastric cancer patients in the Affiliated Cancer Hospital of Nanjing Medical University from January 2017 to January 2019, were randomly divided into control group (50 patients given dexamethasone + parlour SiQiong), and treatment group (50 patients given his minions horse temple + dexamethasone + parlour SiQiong). Recording of nausea and vomiting, as well as adverse reaction of patients, were started after 7 days of chemotherapy in patients. Results: The total effective control of acute CINV in the control group was 82 %, while the total effective control of acute CINV in the study group was 94 %. Values of total effective control of DFS in the control and study groups were 70 and 86 %, respectively. The incidence of adverse reactions was similar in the two groups. There was a significant correlation between the anti-emetic effect of aprepitant and gastric surgery. Conclusion: After gastric cancer surgery, combined treatment with aprepitant, palonosetron and dexamethasone prevents CINV induced by moderate emetogenic chemotherapy with orisaplatin. The combined treatment has good efficacy and can improve tolerance to, and compliance with chemotherap

The complete assembly of human LAT1-4F2hc complex provides insights into its regulation, function and localisation

The LAT1-4F2hc complex (SLC7A5-SLC3A2) facilitates uptake of essential amino acids, hormones and drugs. Its dysfunction is associated with many cancers and immune/neurological disorders. Here, we apply native mass spectrometry (MS)-based approaches to provide evidence of super-dimer formation (LAT1-4F2hc)2. When combined with lipidomics, and site-directed mutagenesis, we discover four endogenous phosphatidylethanolamine (PE) molecules at the interface and C-terminus of both LAT1 subunits. We find that interfacial PE binding is regulated by 4F2hc-R183 and is critical for regulation of palmitoylation on neighbouring LAT1-C187. Combining native MS with mass photometry (MP), we reveal that super-dimerization is sensitive to pH, and modulated by complex N-glycans on the 4F2hc subunit. We further validate the dynamic assemblies of LAT1-4F2hc on plasma membrane and in the lysosome. Together our results link PTM and lipid binding with regulation and localisation of the LAT1-4F2hc super-dimer

Structural Basis for the Enhanced Infectivity and Immune Evasion of Omicron Subvariants

The Omicron variants of SARS-CoV-2 have emerged as the dominant strains worldwide, causing the COVID-19 pandemic. Each Omicron subvariant contains at least 30 mutations on the spike protein (S protein) compared to the original wild-type (WT) strain. Here we report the cryo-EM structures of the trimeric S proteins from the BA.1, BA.2, BA.3, and BA.4/BA.5 subvariants, with BA.4 and BA.5 sharing the same S protein mutations, each in complex with the surface receptor ACE2. All three receptor-binding domains of the S protein from BA.2 and BA.4/BA.5 are “up”, while the BA.1 S protein has two “up” and one “down”. The BA.3 S protein displays increased heterogeneity, with the majority in the all “up” RBD state. The different conformations preferences of the S protein are consistent with their varied transmissibility. By analyzing the position of the glycan modification on Asn343, which is located at the S309 epitopes, we have uncovered the underlying immune evasion mechanism of the Omicron subvariants. Our findings provide a molecular basis of high infectivity and immune evasion of Omicron subvariants, thereby offering insights into potential therapeutic interventions against SARS-CoV-2 variants

Elucidating the strain–vacancy–activity relationship on structurally deformed Co@CoO nanosheets for aqueous phase reforming of formaldehyde

Lattice strain modulation and vacancy engineering are both effective approaches to control the catalytic properties of heterogeneous catalysts. Here, Co@CoO heterointerface catalysts are prepared via the controlled reduction of CoO nanosheets. The experimental quantifications of lattice strain and oxygen vacancy concentration on CoO, as well as the charge transfer across the Co-CoO interface are all linearly correlated to the catalytic activity toward the aqueous phase reforming of formaldehyde to produce hydrogen. Mechanistic investigations by spectroscopic measurements and density functional theory calculations elucidate the bifunctional nature of the oxygen-vacancy-rich Co-CoO interfaces, where the Co and the CoO sites are responsible for CH bond cleavage and OH activation, respectively. Optimal catalytic activity is achieved by the sample reduced at 350 °C, Co@CoO-350 which exhibits the maximum concentration of Co-CoO interfaces, the maximum concentration of oxygen vacancies, a lattice strain of 5.2% in CoO, and the highest aqueous phase formaldehyde reforming turnover frequency of 50.4 h-1 at room temperature. This work provides not only new insights into the strain-vacancy-activity relationship at bifunctional catalytic interfaces, but also a facile synthetic approach to prepare heterostructures with highly tunable catalytic activities.National Research Foundation (NRF)Submitted/Accepted versionThe authors are grateful for financial supports from the National Natural Science Foundation of China (Grant No. 21872123, and 22172143), the Zhejiang Provincial Natural Science Foundation of China (Grant No. LY18B030007), and the Excellent Postgraduate Thesis Program of Zhejiang Sci-Tech University (Grant No. 2019D05). W.L. acknowledges funding from the National Research Foundation of Singapore under its Campus for Research Excellence and Technological Enterprise (CREATE) program

The cryo-EM structure of homotetrameric attachment glycoprotein from langya henipavirus

Abstract Langya Henipavirus (LayV) infection is an emerging zoonotic disease that has been causing respiratory symptoms in China since 2019. For virus entry, LayV’s genome encodes the fusion protein F and the attachment glycoprotein G. However, the structural and functional information regarding LayV-G remains unclear. In this study, we revealed that LayV-G cannot bind to the receptors found in other HNVs, such as ephrin B2/B3, and it shows different antigenicity from HeV-G and NiV-G. Furthermore, we determined the near full-length structure of LayV-G, which displays a distinct mushroom-shaped configuration, distinguishing it from other attachment glycoproteins of HNV. The stalk and transmembrane regions resemble the stem and root of mushroom and four downward-tilted head domains as mushroom cap potentially interact with the F protein and influence membrane fusion process. Our findings enhance the understanding of emerging HNVs that cause human diseases through zoonotic transmission and provide implication for LayV related vaccine development