One-pot synthesis of N-doped petroleum coke-based microporous carbon for high-performance CO2 adsorption and supercapacitors.

Waste resource utilization of petroleum coke is crucial for achieving global carbon emission reduction. Herein, a series of N-doped microporous carbons were fabricated from petroleum coke using a one-pot synthesis method. The as-prepared samples had a large specific surface area (up to 2512 m2/g), a moderate-high N content (up to 4.82 at.%), and high population (55%) of ultra-micropores (<0.7 nm). Regulating the N content and ultra-microporosity led to efficient CO2 adsorption and separation. At ambient pressure, the optimal N-doped petroleum coke-based microporous carbon exhibited the highest CO2 uptake of 4.25 mmol/g at 25°C and 6.57 mmol/g at 0°C. These values are comparable or even better than those of numerous previously reported adsorbents prepared by multistep synthesis, primarily due to the existence of ultra-micropores. The sample exhibited excellent CO2/N2 selectivity at 25°C owing to the abundant basic pyridinic and pyrrolic N species; and showed superior CO2 adsorption-desorption cycling performance, which was maintained at 97% after 10 cycles at 25°C. Moreover, petroleum coke-based microporous carbon, with a considerably high specific surface area and hierarchical pore structure, exhibited excellent electrochemical performance over the N-doped sample, maintaining a favorable specific capacitance of 233.25 F/g at 0.5 A/g in 6 mol/L KOH aqueous electrolyte. This study provides insight into the influence of N-doping on the porous properties of petroleum coke-based carbon. Furthermore, the as-prepared carbons were found to be promising adsorbents for CO2 adsorption, CO2/N2 separation and electrochemical application.

Scalable Fabrication of Superhydrophobic Coating with Rough Coral Reef-Like Structures for Efficient Self-Cleaning and Oil-Water Separation: An Experimental and Molecular Dynamics Simulation Study.

Superhydrophobic coating has a great application prospect in self-cleaning and oil-water separation but remains challenging for large-scale preparation of robust and weather-resistant superhydrophobic coatings via facile approaches. Herein, this work reports a scalable fabrication of weather-resistant superhydrophobic coating with multiscale rough coral reef-like structures by spraying the suspension containing superhydrophobic silica nanoparticles and industrial coating varnish on various substrates. The coral reef-like structures effectively improves the surface roughness and abrasion resistance. Rapid aging experiments (3000 h) and the outdoor building project application (3000 m2 ) show that the sprayed superhydrophobic coating exhibits excellent self-cleaning properties, weather resistance, and environmental adaptability. Moreover, the combined silica-coating varnish-polyurethane (CSCP) superhydrophobic sponge exhibits exceptional oil-water separation capabilities, selectively absorbing the oils from water up to 39 times of its own weight. Furthermore, the molecular dynamics (MD) simulation reveals that the combined effect of higher surface roughness, smaller diffusion coefficient of water molecules, and weaker electrostatic interactions between water and the surface jointly determines the superhydrophobicity of the prepared coating. This work deepens the understanding of the anti-wetting mechanism of superhydrophobic surfaces from the perspective of energetic and kinetic properties, thereby paving the way for the rational design of superhydrophobic materials and their large-scale applications.

Construction of a novel TROP2/CD3 bispecific antibody with potent antitumor activity and reduced induction of Th1 cytokines.

Many cancers, including triple-negative breast cancer, overexpress TROP2 on the surface of tumor cells. TROP2 has become a promising tumor associated antigen for the development of novel antibody-based targeted therapy. Herein, we constructed a novel bispecific antibody with the ability to simultaneously target TROP2 on the tumor surface and bind to CD3 to activate T cells. Given that the excessive production of Th1 cytokines induced by CD3-mediated T-cell overactivation may lead to toxicity in the clinic, we devised a strategy to modify this CD3-induced T cell activation by a two-step reduction in the bispecific antibody binding affinity for CD3 to a level that retained the ability of the bispecific antibody to effectively inhibit tumor growth while greatly reducing the amount of Th1 cytokines secreted by T cells. Thus, we provide insight into the design of T cell engagers that exhibit a promising toxicity profile while retaining inhibitory effects on tumor growth.

Tuning the Hierarchical Pore Structure and the Metal Site in a Metal-Organic Framework Derivative to Unravel the Mechanism for the Adsorption of Different Volatile Organic Compounds.

Volatile organic compounds (VOCs) are one of the main classes of air pollutants, and it is important to develop efficient adsorbents to remove them from the atmosphere. To do this most efficiently, we need to understand the mechanism of VOC adsorption. In this work, we described how the metal organic framework (MOF), ZIF-8, was used as a precursor to generate MOF derivatives (Zn-GC) through temperature-controlled calcination, which had adjustable metal sites and hierarchical pore structure. It was used as a model adsorbent to study the adsorption and desorption characteristics of different VOCs. Zn-GC-850 with developed pores exhibited higher adsorption performance for the benzene series, whereas Zn-GC-650 with more metal sites had a better adsorption capacity for oxygen-containing VOCs. By tuning the molecular structure of the VOCs, we revealed the adsorption mechanism of different VOCs at the molecular level. The more developed hierarchical pore structure obtained at the higher temperature facilitates the diffusion of the benzene series, and the noncovalent interaction between their methyl group(s) and the carbonized MOF derivatives improves the adsorption affinity; while the higher exposure of Zn sites obtained at lower temperature favors the adsorption of oxygen-containing VOCs by Zn-O bonds. The mass transfers of VOCs and the role of the adsorbent were simulated by multiple theoretical models. This study strengthens the basis for the design and optimization of the adsorbent and catalyst for VOCs treatment.

Efficacy and Safety of Coronary Intervention via Distal Transradial Access (dTRA) in Patients with Low Body Mass Index.

The study aimed to investigate the efficacy and safety of coronary intervention via distal transradial access (dTRA) in patients with low body mass index (BMI). A total of 67 patients with low BMI who underwent coronary intervention, comprising 29 patients via dTRA and 38 patients via conventional transradial access (cTRA), were retrospectively included. There was no significant difference in the puncture success rate between the two groups (dTRA 96.6%, cTRA 97.4%, P=0.846). Compared with the cTRA group, the success rate of one-needle puncture in the dTRA group was lower (51.7% vs. 81.6%, P=0.020). The compression haemostasis time in the dTRA group was shorter than that in the cTRA group (P < 0.001). However, the incidence of radial artery occlusion was lower in the dTRA group than in the cTRA group (4.0% vs. 33.3%, P=0.007). In conclusion, coronary intervention via dTRA was safe and effective in patients with low BMI.

Safety and efficacy of coronary angiography and percutaneous coronary intervention via distal transradial artery access in the anatomical snuffbox: a single-centre prospective cohort study using a propensity score method.

BACKGROUND: This study investigated the safety and efficacy of coronary angiography (CAG) and percutaneous coronary intervention (PCI) via distal transradial artery access (d-TRA). METHODS: For this single-centre prospective cohort study, a total of 1066 patients who underwent CAG or PCI procedures from September 2019 to November 2020 were included. Patients were divided into two groups: the d-TRA group (346) and the conventional transradial artery access (c-TRA) group (720) based on access site. A total of 342 pairs of patients were successfully matched using propensity score matching (PSM) for subsequent analysis. RESULTS: No significant differences in puncture success rate, procedural method, procedural time, sheath size, contrast dosage or fluoroscopy time were noted between the two groups. The puncture time in the d-TRA group was longer than that in the c-TRA group (P < 0.01), and the procedure success rate was lower than that in the c-TRA group (90.94% vs. 96.49%, P = 0.01). The haemostasis time in the d-TRA group was shorter than that in the c-TRA group (P < 0.01), and the visual analogue scale (VAS) was lower than that in the c-TRA group (P < 0.01). In addition, the prevalence of bleeding and haematoma in the d-TRA group was lower than that in the c-TRA group (1.75% vs. 7.31%, P < 0.01; 0.58% vs. 3.22%, P = 0.01, respectively). No significant difference in the incidence of numbness was noted between the two groups. No other complications were found in two groups. CONCLUSION: d-TRA is as safe and effective as c-TRA for CAG and PCI. It has the advantages of improved comfort and fewer complications. Trail registration Chinese Clinical Trial Registry, ChiCTR1900026519.

Bispecific antibody simultaneously targeting PD1 and HER2 inhibits tumor growth via direct tumor cell killing in combination with PD1/PDL1 blockade and HER2 inhibition.

Immune checkpoint blockade has shown significant clinical benefit in multiple cancer indications, but many patients are either refractory or become resistant to the treatment over time. HER2/neu oncogene overexpressed in invasive breast cancer patients associates with more aggressive diseases and poor prognosis. Anti-HER2 mAbs, such as trastuzumab, are currently the standard of care for HER2-overexpressing cancers, but the response rates are below 30% and patients generally suffer relapse within a year. In this study we developed a bispecific antibody (BsAb) simultaneously targeting both PD1 and HER2 in an attempt to combine HER2-targeted therapy with immune checkpoint blockade for treating HER2-positive solid tumors. The BsAb was constructed by fusing scFvs (anti-PD1) with the effector-functional Fc of an IgG (trastuzumab) via a flexible peptide linker. We showed that the BsAb bound to human HER2 and PD1 with high affinities (EC50 values were 0.2 and 0.14 nM, respectively), and exhibited potent antitumor activities in vitro and in vivo. Furthermore, we demonstrated that the BsAb exhibited both HER2 and PD1 blockade activities and was effective in killing HER2-positive tumor cells via antibody-dependent cellular cytotoxicity. In addition, the BsAb could crosslink HER2-positive tumor cells with T cells to form PD1 immunological synapses that directed tumor cell killing without the need of antigen presentation. Thus, the BsAb is a new promising approach for treating late-stage metastatic HER2-positive cancers.

Recanalization of the occluded radial artery via distal transradial access in the anatomic snuffbox.

BACKGROUND: Radial artery occlusion is a common complication after coronary angiography and percutaneous coronary intervention via the transradial access. In recent years, coronary angiography and percutaneous coronary intervention via the distal transradial access has gradually emerged, but recanalization of the occluded radial artery through the distal transradial access has rarely been reported. CASE PRESENTATION: A 67-year-old female with arterial hypertension and diabetes mellitus was admitted to the hospital due to chest pain for three hours. She was diagnosed with acute myocardial infarction. After admission, the patient successfully underwent emergency coronary angiography and percutaneous coronary intervention through the right transradial access. Radial artery occlusion was found after the operation, and recanalization was successfully performed through the right distal transradial access before discharge. Immediately after the operation and one month later, vascular ultrasonography showed that the antegrade flow was normal. CONCLUSIONS: This report presents a case of radial artery occlusion after emergency coronary angiography and percutaneous coronary intervention in which recanalization was successfully performed through the right distal transradial access. This case demonstrates that recanalization of a radial artery occlusion via the distal transradial access is safe and feasible.

Atherogenic index of plasma is related to coronary atherosclerotic disease in elderly individuals: a cross-sectional study.

BACKGROUND: Dyslipidaemia plays an important role in coronary atherosclerotic disease (CAD). The relationship between the atherogenic index of plasma (AIP) and CAD in elderly individuals was explored in this study. METHODS: Elderly individuals (age ≥ 65 years) who underwent coronary angiography from January 2016 to October 2020 were consecutively enrolled in the study. RESULTS: A total of 1313 individuals, including 354 controls (non-CAD) and 959 CAD patients, were enrolled. In univariate analysis of all populations, the adjusted AIP (aAIP) in the CAD group was 1.13 (0.96, 1.3), which was significantly higher than that in the controls [1.07 (0.89, 1.26)]. However, in subgroup analyses, this phenomenon was only present in males. In addition, further study showed that aAIP was positively related to CAD severity. In binary logistic regression analyses, after adjusting for sex, age, smoking status, primary hypertension (PH), type 2 diabetes mellitus (T2DM), heart rate (HR), white blood cell (WBC) and platelet (PLT), AIP remained independently related to CAD in elderly individuals and was superior to traditional and other nontraditional lipid indices. Subgroup analyses showed that AIP independently influenced CAD risk in males. Ultimately, sensitivity analyses were performed excluding all coronary emergencies, and the final results were similar. CONCLUSIONS: AIP was positively related to the risk and severity of CAD in elderly individuals and was superior to traditional and other nontraditional lipid profiles. However, this association only exists in elderly males.

Volatile organic compounds concentration profiles and control strategy in container manufacturing industry: Case studies in China.

Volatile organic compounds (VOCs), important precursors of ozone (O3) and fine particulate matter (PM2.5), are the key to curb the momentum of O3 growth and further reducing PM2.5 in China. Container manufacturing industry is one of the major VOC emitters, and more than 96% containers of the world are produced in China, with the annual usage of coatings of over 200,000 tons in recent years. This is the first research on the emission characteristics of VOCs in Chinese container manufacturing industry, including concentration and ozone formation potential (OFP) of each species. The result shows that the largest amounts of VOCs are emitted during the pretreatment process, followed by the paint mixing process and primer painting process, and finally other sprays process. The average VOC concentrations in the workshops, the exhausts before treatment and the exhausts after treatment are ranging from 82.67-797.46 , 170-1,812.65 , 66.20-349.63 mg/m3, respectively. Benzenes, alcohols and ethers are main species, which contribute more than 90% OFP together. Based on the emission characteristics of VOCs and the technical feasibility, it is recommended to set the emission limit in standard of benzene to 1.0 mg/m3, toluene to 10 mg/m3, xylene to 20 mg/m3, benzenes to 40 mg/m3, alcohols and ethers to 50 mg/m3, and VOCs to 100 mg/m3. The study reports the industry emission characteristics and discusses the standard limits, which is a powerful support to promote VOCs emission reduction, and to promote the coordinated control of PM2.5 and O3 pollution.

Distal transradial access: a review of the feasibility and safety in cardiovascular angiography and intervention.

BACKGROUND: Transradial access (TRA) has been considered as the default choice in cardiac catheterization. Although infrequent, vascular complications of this approach remain. Recently, the distal transradial approach (dTRA) in cardiac catheterization was reported by interventionalists. METHODS: We retrieved the relevant literatures and reviewed the safety and feasibility of this novel approach in cardiac catheterization. RESULTS: The dTRA for cardiac intervention has superior safety and satisfaction. As a novel approach for cardiac catheterization, access related complications should also be considered by operators, such as RAO, radial spasm, bleeding and haematoma, and injury of the superficial branch of the radial nerve. CONCLUSIONS: The dTRA in cardiovascular angiography and intervention was safe and feasible.

Microbial Targeted Degradation Pretreatment: A Novel Approach to Preparation of Activated Carbon with Specific Hierarchical Porous Structures, High Surface Areas, and Satisfactory Toluene Adsorption Performance.

Hierarchical porous carbon shows great potential for volatile organic compounds (VOCs) removal due to its high surface area and abundant porous framework. However, current fabrication protocols are complex and cause secondary pollution, limiting their application. Here, as a novel strategy, microbial lignocellulose decomposition as a pretreatment was introduced to fabricate hierarchical porous carbon (M-AC) from crude biomass substrate. The M-AC samples had high specific surface areas (maximum: 2290 m2·g-1) and surfaces characterized by needle-like protrusions with a high degree of disorder attributed to hierarchical porous structures. Dynamic toluene adsorption indicated that the carbon materials with microbial pretreatment had much better adsorption performances (maximum: 446 mg/g) than activated carbon without pretreatment. The M-AC material pretreated with a cellulose-degrading microbe showed the best adsorption capacity due to well-developed micropores, whereas the M-AC material pretreated with a lignin-degrading microbe showed excellent transport diffusion due to well-developed mesopores. Therefore, this simple and effective approach using microbial decomposition pretreatment is promising for the development of hierarchical porous carbons with adjustable pore structures and high specific surface areas to remove target VOCs in practical applications.

Complement C3 gene polymorphisms are associated with lipid levels, but not the risk of coronary artery disease: a case-control study.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. Previous studies have shown that complement component 3 (C3) is associated with atherosclerosis and cardiovascular risk factors. METHODS: We conducted this study to evaluate the associations between tagSNPs in the C3 gene locus and the CAD susceptibility and lipid levels in the Chinese population. A hospital-based case-control study, including 1017 subjects (580 CAD patients and 437 non-CAD controls), was conducted. TagSNPs in the C3 gene were searched and genotyped by using the polymerase chain reaction-ligase detection reaction method. RESULTS: The C3 levels were positively associated with the low-density lipoprotein cholesterol (LDL-C) levels (r = 0.269, P = 0.001). Compared with those in controls, the serum C3 levels in CAD patients were significantly higher (Control: 0.94 + 0.14 g/l; CAD: 1.10 + 0.19 g/l, P < 0.001). No significant differences in genotype or allele frequencies were observed between CAD patients and controls. The minor T allele of rs2287848 was associated with low apolipoprotein A1 (ApoA1) levels in controls (Bonferroni corrected P, Pc = 0.032). Linkage disequilibrium and haplotype analysis established two haplotype blocks (Block1: rs344555-rs2277984, Block 2: rs2287848-rs11672613) and six haplotypes. No significant associations between haplotypes and the risk of CAD were observed (all Pc > 0.05). CONCLUSIONS: The results revealed that C3 gene polymorphisms were associated with the lipid levels, but not CAD susceptibility in the Chinese population.

A novel strategy to produce high level and high purity of bioactive IL15 fusion proteins from mammalian cells.

IL15, a member of the common γ chain receptor (γc) cytokine family, is gaining attention in recent years as one of the most promising anti-tumor agents. IL15 regulates T cell activation and proliferation, promotes the survival of CD8+ CD44hi memory T cells and is also essential for NK cell expansion and development. Despite the attraction of developing IL15 as an anti-cancer agent, production of recombinant IL15 has proven to be difficult due to the stringent control of IL15 expression at the transcriptional, translational and the post-translational levels. Furthermore, the bioactivity of IL15 fused to an extra functional domain that is isolated from mammalian cells is generally inferior to recombinant IL15 produced by E. coli. In this study, we report that Lysine 86 in IL15 is responsible for the instability in mammalian cells when its C-terminus is fused to the albumin binding scFv (IL15-A10m3). We demonstrate that K86A or K86R mutants increased the expression of the fusion protein from HEK293 cells. When the wild type IL15 is used for the fusion, no recombinant IL15 fusion was detected in the culture media. Additionally, we determined that the residue 112 in IL15 is critical for the bioactivity of IL15-A10m3. Examination of single and double mutants provides a better understanding of how IL15 engages with its receptor complex to achieve full signaling capacity. The results of our experiments were successfully applied to scale up production to levels up to 50 mg/L and >10 mg/L of >95% pure monomeric recombinant fusion proteins after a 2-step purification from culture media. More importantly, the recombinant fusion protein produced is fully active in stimulating T cell proliferation, when compared to the recombinant wild type IL15.

A pair of chiral flavonolignans as novel anti-cyanobacterial allelochemicals derived from barley straw (Hordeum vulgare): characterization and comparison of their anti-cyanobacterial activities.

The inhibitory effect of barley straw (Hordeum vulgare) on cyanobacteria has been observed in many field and laboratory studies for over 30 years, although the compounds responsible for this anti-cyanobacterial effect have remained unknown. In this study, a pair of chiral flavonolignans were isolated from barley straw extract using a bioassay-guided isolation procedure against Microcystis sp. The structures of the allelopathic compounds were elucidated by NMR (nuclear magnetic resonance) and HPLC-MS (high performance liquid chromatography-mass spectrometry), and turned out to be salcolin A and B. The enantiomers differ in their anti-cyanobacterial abilities. Both enantiomers exhibited inhibitory effects on Microcystis sp., and the EC50 (concentration for 50% of maximal effect) of salcolin A and B were 6.02 × 10(-5) and 9.60 × 10(-5 ) mol l(-1) , respectively. Furthermore, the modes of actions of the enantiomers were investigated and compared at a single cell level by flow cytometry. Salcolin A was found to induce an increase on cyanobacterial intracellular ROS (reactive oxygen species) levels and to inhibit esterase activity, whereas salcolin B caused leakages of cyanobacterial cytoplasms. Thus, salcolin A was more 'algistatic', and salcolin B was more 'algicidal'. This study suggests that salcolin is the key allelochemical in barley straw's inhibitory effect on cyanobacteria and could be used as an agent in the future control of cyanobacterial harmful algae blooms.

Replication stress and mitotic dysfunction in cells expressing simian virus 40 large T antigen.

We previously demonstrated that simian virus 40 (SV40) large T antigen (LT) binds to the Bub1 kinase, a key regulator of the spindle checkpoint and chromosome segregation. Bub1 mutations or altered expression patterns are linked to chromosome missegregation and are considered to be a driving force in some human cancers. Here we report that LT, dependent on Bub1 binding, causes micronuclei, lagging chromatin, and anaphase bridges, which are hallmarks of chromosomal instability (CIN) and Bub1 insufficiency. Using time-lapse microscopy, we demonstrate that LT imposes a Bub1 binding-dependent delay in the metaphase-to-anaphase transition. Kinetochore fibers reveal that LT, via Bub1 binding, causes aberrant kinetochore (KT)-microtubule (MT) attachments and a shortened interkinetochore distance, consistent with a lack of tension. Previously, we showed that LT also induces the DNA damage response (DDR) via Bub1 binding. Using inducible LT cell lines, we show that an activated DDR was observed before the appearance of anaphase bridges and micronuclei. Furthermore, LT induction in serum-starved cells demonstrated γ-H2AX accumulation in cells that had not yet entered mitosis. Thus, DDR activation can occur independently of chromosome segregation defects. Replication stress pathways may be responsible, because signatures of replication stress were observed, which were attenuated by exogenous supplementation with nucleosides. Our observations allow us to propose a model that explains and integrates the diverse manifestations of genomic instability induced by LT.

Identification of NOx emissions and source characteristics by TROPOMI observations - A case study in north-central Henan, China.

With the development of industries, air pollution in north-central Henan is becoming increasingly severe. The TROPOspheric Monitoring Instrument (TROPOMI) provides nitrogen dioxide (NO2) column densities with high spatial resolution. Based on TROPOMI, in this study, the nitrogen oxides (NOx) emissions in north-central Henan are derived and the emission hotspots are identified with the flux divergence method (FDM) from May to September 2021. The results indicate that Zhengzhou has the highest NOx emissions in north-central Henan. The most prominent hotspots are in Guancheng Huizu District (Zhengzhou) and Yindu District (Anyang), with emissions of 448.4 g/s and 300.3 g/s, respectively. The Gaussian Mixture Model (GMM) is applied to quantify the characteristics of emission hotspots, including the diameter, eccentricity, and tilt angle, among which the tilt angle provides a novel metric for identifying the spatial distribution of pollution sources. Furthermore, the results are compared with the CAMS global anthropogenic emissions (CAMS-GLOB-ANT) and Multi-resolution Emission Inventory model for Climate and air pollution research (MEIC), and they are generally in good agreement. However, some point sources, such as power plants, may be missed by both inventories. It is also found that for emission hotspots near transportation hubs, CAMS-GLOB-ANT may not have fully considered the actual traffic flow, leading to an underestimation of transportation emissions. These findings provide key information for the accurate implementation of pollution prevention and control measures, as well as references for future optimization of emission inventories. Consequently, deriving NOx emissions from space, quantifying the characteristics of emission hotspots, and combining them with bottom-up inventories can provide valuable insights for targeted emission control.

Investigation of catalytic methane oxidation over Ag/Co2MOx (M = Co, Ni, Cu) catalysts with varying interfacial electron transfer.

Atom-doped Co3O4 catalysts loaded with Ag were examined as cost-effective catalysts for methane oxidation. The synthesized Ag/Co2NiOx catalysts exhibited distinctive surface characteristics in contrast with Ag/Co3O4 and Ag/Co2CuOx catalysts prepared using a similar method. Characterization results unveiled that Ag/Co2NiOx featured a higher presence of active surface oxygen species, lattice defects, a larger surface area, and enhanced reducibility. A methane oxidation catalytic performance followed the sequence: Ag/Co2NiOx > Ag/Co3O4 > Ag/Co2CuOx. The investigation delved into methane degradation pathways on the surfaces of three catalysts, examining their behavior under both aerobic and anaerobic atmospheres through in-situ DRIFTS analysis. Furthermore, introducing Ag showed a marked positive effect on Co-Ni mixed oxide, inducing electron transfer and a more active electron system, whereas it exhibited an inverse impact within the surface of Co-Cu mixed oxide. This work provides innovative perspectives on the development of forthcoming environmental catalysts.

Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1.

The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most therapeutic mAbs have been evaded. Addressing this challenge, we systematically explored a reproducible bispecific antibody (bsAb)-dependent synergistic effect in this study. It could effectively restore the neutralizing activity of the bsAb when any of its single mAbs is escaped by variants. This synergy is primarily attributed to the binding angle of receptor-binding domain (RBD)-5, facilitating inter-spike cross-linking and promoting cryptic epitope exposure that classical antibody cocktails cannot achieve. Furthermore, RBD-5 with RBD-2, RBD-6, and RBD-7, alongside RBD-8, also exhibit significantly enhanced effects. This study not only shifts the paradigm in understanding antibody interactions but paves the way for developing more effective therapeutic antibodies against rapidly mutating SARS-CoV-2, with Dia-19 already showing promise against emerging variants like BA.2.86, EG.5.1, and JN.1.

Systemic investigation of inetetamab in combination with small molecules to treat HER2-overexpressing breast and gastric cancers.

Most patients with metastatic breast cancer or gastric cancer who are treated with trastuzumab, an anti-HER2 monoclonal antibody, become refractory to the drug within a year after the initiation of treatment. Although the combination of trastuzumab with pertuzumab produced synergetic effects in the treatment of HER2-overexpressing cancers, not all patients with HER2 overexpression benefited from the trastuzumab plus pertuzumab combination. To improve the clinical benefits of trastuzumab, we systemically investigated the combination of inetetamab (Cipterbin), an analog of trastuzumab, with a variety of small molecules, including tyrosine kinase inhibitors (TKIs) and chemotherapeutic agents in vivo. We showed that pan-TKIs-induced synergistic antitumor effects with inetetamab in the treatment of these two types of cancers and that adding chemotherapeutic agents to the existing TKI plus anti-HER2 monoclonal antibody combination strategies induced additional inhibitory effects, suggesting that such combination strategies may be choices for the treatment of these two tumors. Thus, combination therapies targeting distinct and broad pathways that are essential for tumor growth and survival can be effective for treating metastatic breast cancers and gastric cancers.