Gene redundancy and gene compensation of insulin-like peptides in the oocyte development of bean beetle.

Bean beetle (Callosobruchus maculatus) exhibits clear phenotypic plasticity depending on population density; However, the underlying molecular mechanism remains unknown. Compared to low-density individuals, high-density individuals showed a faster terminal oocyte maturity rate. Four insulin-like peptide (ILP) genes were identified in the bean beetle, which had higher expression levels in the head than in the thorax and abdomen. The population density could regulate the expression levels of CmILP1-3, CmILP2-3, and CmILP1 as well as CmILP3 in the head, thorax, and abdomen, respectively. RNA interference results showed that each CmILP could regulate terminal oocyte maturity rate, indicating that there was functional redundancy among CmILPs. Silencing each CmILP could lead to down-regulation of some other CmILPs, however, CmILP3 was up-regulated in the abdomen after silencing CmILP1 or CmILP2. Compared to single gene silencing, silencing CmILP3 with CmILP1 or CmILP2 at the same time led to more serious retardation in oocyte development, suggesting CmILP3 could be up-regulated to functionally compensate for the down-regulation of CmILP1 and CmILP2. In conclusion, population density-dependent plasticity in terminal oocyte maturity rate of bean beetle was regulated by CmILPs, which exhibited gene redundancy and gene compensation.

Genome analysis and classification of Xanthomonas bacteriophage AhaSv, a new member of the genus Salvovirus.

Xanthomonas phage AhaSv was isolated from lake water. Genome sequencing showed that its genome is a linear dsDNA molecule with a length of 55,576 bp and a G+C content of 63.23%. Seventy-one open reading frames (ORFs) were predicted, and no tRNAs were found in the genome. Phylogenetic analysis showed that AhaSv is closely related to members of the genus Salvovirus of the family Casjensviridae. Intergenomic similarity values between phage AhaSv and homologous phages were up to 90.6%, suggesting that phage AhaSv should be considered a member of a new species in the genus Salvovirus.

Secondary Organic Aerosol Generated from Biomass Burning Emitted Phenolic Compounds: Oxidative Potential, Reactive Oxygen Species, and Cytotoxicity.

Phenolic compounds are largely emitted from biomass burning (BB) and have a significant potential to form SOA (Phc-SOA). However, the toxicological properties of Phc-SOA remain unclear. In this study, phenol and guaiacol were chosen as two representative phenolic gases in BB plumes, and the toxicological properties of water-soluble components of their SOA generated under different photochemical ages and NOx levels were investigated. Phenolic compounds contribute greatly to the oxidative potential (OP) of biomass-burning SOA. OH-adducts of guaiacol (e.g., 2-methoxyhydroquinone) were identified as components of guaiacol SOA (GSOA) with high OP. The addition of nitro groups to 2,5-dimethyl-1,4-benzoquinone, a surrogate quinone compound in Phc-SOA, increased its OP. The toxicity of both phenol SOA (PSOA) and GSOA in vitro in human alveolar epithelial cells decreased with aging in terms of both cell death and cellular reactive oxygen species (ROS), possibly due to more ring-opening products with relatively low toxicity. The influence of NOx was consistent between cell death and cellular ROS for GSOA but not for PSOA, indicating that cellular ROS production does not necessarily represent all processes contributing to cell death caused by PSOA. Combining different acellular and cellular assays can provide a comprehensive understanding of aerosol toxicological properties.

Application of cold-adapted microbial agents in soil contaminate remediation: biodegradation mechanisms, case studies, and safety assessments.

The microbial agent technology has made significant progress in remediating nitro-aromatic compounds (NACs), such as p-nitrophenol, 2,4-dinitrophenol, and 2,4,6-Trinitrotoluene, in farmland soil over the past decade. However, there are still gaps in our understanding of the bioavailability and degradation mechanisms of these compounds in low-temperature environments. In this review, we provide a comprehensive summary of the strategies employed by cold-adapted microorganisms and elucidate the degradation pathways of NACs pollutants. To further analyze their metabolic mechanisms, we propose using mass balance to improve our understanding of biochemical processes and refine the degradation pathways through stoichiometry analysis. Additionally, we suggest employing 13C-metabolic flux analysis to track enzyme activity and intermediate products during bio-degradation processes with the aim of accelerating the remediation of nitro-aromatic compounds, particularly in cold regions. Through a comprehensive analysis of pollutant metabolic activities and a commitment to the 'One Health' approach, with an emphasis on selecting non-pathogenic strains, the environmental management strategies for soil remediation could be positioned to develop and implement safe and effective measure.

Increased levels of villus-derived exosomal miR-29a-3p in normal pregnancy than uRPL patients suppresses decidual NK cell production of interferon-γ and exerts a therapeutic effect in abortion-prone mice.

OBJECTIVE: Recurrent pregnancy loss (RPL) patients have higher absolute numbers of decidual natural killer (dNK) cells with elevated intracellular IFN-γ levels leading to a pro-inflammatory cytokine milieu, which contributes to RPL pathogenesis. The main objective of this study was twofold: first to explore the regulatory effects and mechanisms of villus-derived exosomes (vEXOs) from induced abortion patients or RPL patients at the level of intracellular IFN-γ in dNK cells; second to determine the validity of application of vEXOs in the treatment of unexplained RPL (uRPL) through in vitro experiments and mouse models. METHODS: Exosomes were isolated from villus explants by ultracentrifugation, co-cultured with dNK cells, and purified by enzymatic digestion and magnetically activated cell sorting. Flow cytometry, enzyme-linked immunosorbent assays, and RT-qPCR were used to determine IFN-γ levels. Comparative miRNA analysis of vEXOs from induced abortion (IA) and uRPL patients was used to screen potential candidates involved in dNK regulation, which was further confirmed by luciferase reporter assays. IA-vEXOs were electroporated with therapeutic miRNAs and encapsulated in a China Food and Drug Administration (CFDA)-approved hyaluronate gel (HA-Gel), which has been used as a clinical biomaterial in cell therapy for > 30 years. In vivo tracking was performed using 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyaine iodide (DiR) labelling. Tail-vein and uterine horn injections were used to evaluate therapeutic effects of the engineered exosomes in an abortion-prone mouse model (CBA/J × DBA/2 J). Placental growth was evaluated based on placental weight. IFN-γ mRNA levels in mouse placentas were measured by RT-qPCR. RESULTS: IFN-γ levels were significantly higher in dNK cells of uRPL patients than in IA patients. Both uRPL-vEXOs and IA-vEXOs could be efficiently internalized by dNK cells, whereas uRPL-vEXOs could not reduce the expression of IFN-γ by dNK cells as much as IA-vEXOs. Mechanistically, miR-29a-3p was delivered by vEXOs to inhibit IFN-γ production by binding to the 3' UTR of IFN-γ mRNA in dNK cells. For in vivo treatment, application of the HA-Gel effectively prolonged the residence time of vEXOs in the uterine cavity via sustained release. Engineered vEXOs loaded with miR-29a-3p reduced the embryo resorption rate in RPL mice with no signs of systemic toxicity. CONCLUSION: Our study provides the first evidence that villi can regulate dNK cell production of IFN-γ via exosome-mediated transfer of miR-29a-3p, which deepens our understanding of maternal-fetal immune tolerance for pregnancy maintenance. Based on this, we developed a new strategy to mix engineered vEXOs with HA-Gel, which exhibited good therapeutic effects in mice with uRPL and could be used for potential clinical applications in uRPL treatment.

A novel magnetic graphene-loaded biochar gel for the remediation of arsenic- and antimony-contaminated mining soil.

Metalloid co-contamination such as arsenic (As) and antimony (Sb) in soils has posed a significant threat to ecological balance and human well-being. In this study, a novel magnetic graphene-loaded biochar gel (FeBG) was developed, and its remediation potential for the reclamation of AsSb spoiled soil was assessed through a six-month soil incubation experiment. Results showed that the incorporation of iron substances and graphene imparted FeBG with enhanced surface characteristics, such as the formation of a new FeO bond and an enlarged surface area compared to the pristine biochar (BC) (80.5 m2 g-1 vs 57.4 m2 g-1). Application of FeBG significantly decreased Na2HPO4-extractable concentration of As in soils by 9.9 %, whilst BC addition had a non-significant influence on As availability, compared to the control. Additionally, both BC (8.2 %) and FeBG (16.4 %) treatments decreased the Na2HPO4-extractable concentration of Sb in soils. The enhanced immobilization efficiency of FeBG for As/Sb could be attributed to FeBG-induced electrostatic attraction, complexation (Fe-O(H)-As/Sb), and π-π electron donor-acceptor coordination mechanisms. Additionally, the FeBG application boosted the activities of sucrase (9.6 %) and leucine aminopeptidase (7.7 %), compared to the control. PLS-PM analysis revealed a significant negative impact of soil physicochemical properties on the availability of As (ß = -0.611, P < 0.01) and Sb (ß = -0.848, P < 0.001) in soils, in which Sb availability subsequently led to a suppression in soil enzyme activities (ß = -0.514, P < 0.01). Overall, the novel FeBG could be a potential amendment for the simultaneous stabilization of As/Sb and the improvement of soil quality in contaminated soils.

Iron-Catalyzed Aminoalkylative Carbonylative Cyclization of Alkenes toward α-Tetralones.

Carbonylative multifunctionalization of alkenes is an efficient approach to introduce multiple functional groups into one molecule from easily available materials. Herein, we developed an iron-catalyzed radical relay carbonylative cyclization of alkenes with acetamides. Various α-tetralones can be constructed in moderate yields from readily available substrates with an earth-abundant iron salt as the catalyst.

TSG6-Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model.

Intrauterine adhesion (IUA) is characterized by the formation of fibrous scar tissue within the uterine cavity, which significantly impacts female reproductive health and even leads to infertility. Unfortunately, severe cases of IUA currently lack effective treatments. This study presents a novel approach that utilizes tumor necrosis factor-(TNF) stimulated gene 6 (TSG6)-modified exosomes (Exos) in conjunction with an injectable thermosensitive hydrogel (CS/GP) to mitigate the occurrence of IUA by reducing endometrium fibrosis in a mouse IUA model. This study demonstrate that TSG6-modified Exos effectively inhibits the activation of inflammatory M1-like macrophages during the initial stages of inflammation and maintains the balance of macrophage phenotypes (M1/M2) during the repair phase. Moreover, TSG6 inhibits the interaction between macrophages and endometrial stromal fibroblasts, thereby preventing the activation of stromal fibroblasts into myofibroblasts. Furthermore, this research indicates that CS/GP facilitates the sustained release of TSG6-modified Exos, leading to a significant reduction in both the manifestations of IUA and the extent of endometrium fibrosis. Collectively, through the successful construction of CS/GP loaded with TSG6-modified Exos, a reduction in the occurrence and progression of IUA is achieved by mitigating endometrium fibrosis. Consequently, this approach holds promise for the treatment of IUA.

Tibial tubercle avulsion fracture following preexisting Osgood-Schlatter disease in an adolescent: a case report.

Tibial tubercle avulsion fractures (TTAFs) are rare but typical in children and adolescents and Osgood-Schlatter disease (OSD) may be involved in their pathogenesis. However, few publications have reported the relationship between OSD and TTAF. A 16-year-old healthy male adolescent presented with pain, swelling and limited range of motion of the right knee following sudden acceleration while running. Based on the radiographic evidence, the patient was diagnosed with an avulsion fracture of the right tibial tubercle and OSD. Open reduction and internal fixation were performed using two cannulated screws and two Kirschner wires. The patient returned to preinjury activity levels at the 12-month follow-up postoperatively. This case report aimed to highlight this unique injury pattern. For patients with TTAFs, not only should the fracture be treated, but the cause of the fracture, such as OSD, should also be given appropriate treatment.

Characteristics and whole-genome analysis of a novel Pseudomonas syringae pv. tomato bacteriophage D6 isolated from a karst cave.

Pseudomonas syringae is a gram-negative plant pathogen that infects plants such as tomato and poses a threat to global crop production. In this study, a novel lytic phage infecting P. syringae pv. tomato DC3000, named phage D6, was isolated and characterized from sediments in a karst cave. The latent period of phage D6 was found to be 60 min, with a burst size of 16 plaque-forming units per cell. Phage D6 was stable at temperatures between 4 and 40 °C but lost infectivity when heated to 70 °C. Its infectivity was unaffected at pH 6-10 but became inactivated at pH ≤ 5 or ≥ 12. The genome of phage D6 is a linear double-stranded DNA of 307,402 bp with a G + C content of 48.43%. There is a codon preference between phage D6 and its host, and the translation of phage D6 gene may not be entirely dependent on the tRNA library provided by the host. A total of 410 open reading frames (ORFs) and 14 tRNAs were predicted in its genome, with 92 ORFs encoding proteins with predicted functions. Phage D6 showed low genomic similarity to known phage genomes in the GenBank and Viral sequence databases. Genomic and phylogenetic analyses revealed that phage D6 is a novel phage. The tomato plants were first injected with phage D6, and subsequently with Pst DC3000, using the foliar spraying and root drenching inoculum approach. Results obtained after 14 days indicated that phage D6 inoculation decreased P. syringae-induced symptoms in tomato leaves and inhibited the pathogen's growth in the leaves. The amount of Pst DC3000 was reduced by 150- and 263-fold, respectively. In conclusion, the lytic phage D6 identified in this study belongs to a novel phage within the Caudoviricetes class and has potential for use in biological control of plant diseases.

Bi-2-(2-phenethyl)chromone derivatives from agarwood of Aquilaria filaria in the Philippines.

Twelve undescribed 2-(2-phenethyl)chromone dimers (1-12) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria in the Philippines, guided by a UHPLC-MS analysis. Their structures were elucidated by 1D NMR, 2D NMR, and HR-ESI-MS spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD spectra. Compounds 1, 2, 5 and 9-12 exhibited potent to moderate anti-inflammatory activity with IC50 values in the range of 22.43 ± 0.86 to 53.88 ± 4.06 µM.

Postpartum Necrotizing Myositis With Endometrial Prolapse.

BACKGROUND: Postpartum necrotizing myositis is a rare condition, typically presenting as a complication after uterine artery embolization or uterine compression suturing. Uterine ischemia can cause endometrial necrosis and even myometrial necrosis, which can lead to systemic infection. If a systemic infection is not promptly and actively treated, it may pose significant risk. CASE: A 35-year-old patient who had undergone bilateral uterine artery ligation, modified B-Lynch suture, and multiple compression sutures due to refractory postpartum hemorrhage frequently presented to clinic after postpartum discharge due to persistent fever and vaginal discharge. A bag-like prolapse from the vagina measuring 10×5 cm, accompanied by purulent discharge, was noted 78 days postsurgery. Subsequent pelvic magnetic resonance imaging revealed a uterine basal abscess and postpartum necrotizing myositis; an emergency laparoscopic supracervical hysterectomy was performed, with postoperative pathology confirming the diagnosis. After the patient's discharge, she was readmitted for inpatient treatment of a pelvic abscess. CONCLUSIONS: Although rare, postpartum necrotizing myositis should be considered in postpartum patients presenting with fever, abdominal pain, severe infection symptoms, and abnormal vaginal discharge. Culture and sensitivity testing are recommended to direct appropriate antibiotic therapy.

Development of non-invasive flexible directional microwave ablation for central lung cancer: a simulation study.

Transbronchial microwave ablation (MWA) with flexible antennas has gradually become an attractive alternative to percutaneous MWA for lung cancer due to its characteristic of non-invasiveness. However, flexible antennas for the precision ablation of lung tumors that are adjacent to critical bronchial structures are still not available. In this study, a non-invasive flexible directional (FD) antenna for early stage central lung tumors surrounding the bronchia was proposed. A comprehensive numerical MWA model with the FD antenna was developed in a real human-sized left lung model. The structure of the antenna and the treatment protocol were optimized by a generic algorithm for the precision ablation of two cases of early stage central lung cancer (i.e. spherical-like and ellipsoidal tumors). The electromagnetic efficiency of the optimized antenna was also improved by implementing an optimizedπ-matching network for impedance matching. The results indicate that the electromagnetic energy of MWA can be restricted to a particular area for precision ablation of specific lung tumors using the FD antenna. This study contributes to the field of lung cancer management with MWA.

Generation of porcine circovirus type 4 virus-like particles and their use to detect serum antibodies.

Porcine circovirus type 4 (PCV4), first identified in 2019 as a newly emerging pathogen, has been found in several provinces of China, as well as in Korea and Thailand. Since PCV4 is not included in immunization programs, epidemiological investigations should be conducted for detection of anti-PCV4 antibodies. Virus-like particles (VLPs) are frequently used for serological analysis of pathogen infections. However, there have been no reports on using PCV4 VLPs for serological investigation of PCV4 infection. In this study, we generated self-assembled PCV4 VLPs using an E. coli expression system, purified them using a two-step process, and used them to develop an indirect ELISA. This ELISA method was found to be highly specific, sensitive, and repeatable, making it suitable for PCV4 antibody detection in serum samples. Finally, the ELISA was used to analyze 422 serum samples collected from across several regions in China, 134 of which tested positive. Thus, the PCV4-VLP-based ELISA can effectively detect antibodies against PCV4 in serum samples, making it a useful tool for PCV4 epidemiology.

Energy-growth nexus in Australia and New Zealand for the past 150 years-evidence from time-varying and quantile Granger causality analysis.

Using historical data on energy from (Malanima 2020) and GDP from the Maddison Project Database, this paper investigates the energy-growth nexus in a less-studied region, mainly Australia and New Zealand, since 1870. The long annual series allow meaningful application of recently developed time-varying and quantile Granger causality analysis. Results indicate that there is a bi-directional Granger causal relationship between economic growth and energy, coal, and oil consumption at both ends of the distribution, and during various time periods over the past 150 years. Little evidence is found on the Granger causal relationship from gas consumption to economic growth, but some evidence on the direction from economic growth to gas consumption. The Granger causal relationships between electricity consumption and GDP change over time, but results suggest much closer links between the two in most recent decades, and big (positive and negative) changes in electricity consumption significantly Granger causes economic growth.

The interactive force between fat, oil, and grease (FOG) deposits and the effect of food waste disposers on kitchen drainage systems.

Food waste disposers (FWDs) streamline kitchen waste management and facilitate waste classification, whether they would increase the potential of blockage in kitchen drainage system is still unknown. This study conducted a theoretical analysis of the interactive forces between fat, oil, and grease (FOG) deposits and their aggregation on pipe walls. The study involved grading food waste particles processed by FWDs using sieving and weighing techniques to determine the mean weight diameter (MWD) of various aggregations. A full-scale experimental system, implemented in a 60-m high test tower, simulated blockages in horizontal pipes of high-rise buildings. The effect of pipeline materials and particle sizes on blockage were examined by measuring the adhesion of deposits on horizontal pipes. Energy dispersive spectrometer (EDS) analysis suggested that liquid bridge force is a primary factor in aggregate formation. Hand-cut particles formed aggregates with the highest MWD value. Particle size analysis revealed that sizes ranging from 2.36 to 4.75 mm, 1.18-2.36 mm, and 0.60-1.18 mm constituted over 80 % of particles ground by FWDs, with an average size of 2.16 mm. Results of full-scale experiment indicate particle diameters, friction coefficients and lipophilic coefficient significantly affected the propensity of these aggregates to adhere to pipes. Notably, particles processed by FWDs tended to cause blockages more frequently than hand-cut particles. These findings elucidate the deposition mechanism of FOG deposits and offer strategies to reduce blockages in kitchen drainage systems, such as reducing current grinding particle size by 18 % to 1.77 mm or selecting pipes like cast iron and high-density polyethylene.

Large and Pressure-Dependent c-Axis Piezoresistivity of Highly Oriented Pyrolytic Graphite near Zero Pressure.

The c-axis piezoresistivity is a fundamental and important parameter of graphite, but its value near zero pressure has not been well determined. Herein, a new method for studying the c-axis piezoresistivity of van der Waals materials near zero pressure is developed on the basis of in situ scanning electron microscopy and finite element simulation. The c-axis piezoresistivity of microscale highly oriented pyrolytic graphite (HOPG) is found to show a large value of 5.68 × 10-5 kPa-1 near zero pressure and decreases by 2 orders of magnitude to the established value of ∼10-7 kPa-1 when the pressure increases to 200 MPa. By modulating the serial tunneling barrier model on the basis of the stacking faults, we describe the c-axis electrical transport of HOPG under compression. The large c-axis piezoresistivity near zero pressure and its large decrease in magnitude with pressure are attributed to the rapid stiffening of the electromechanical properties under compression.

A Comprehensive Survey on Deep Graph Representation Learning.

Graph representation learning aims to effectively encode high-dimensional sparse graph-structured data into low-dimensional dense vectors, which is a fundamental task that has been widely studied in a range of fields, including machine learning and data mining. Classic graph embedding methods follow the basic idea that the embedding vectors of interconnected nodes in the graph can still maintain a relatively close distance, thereby preserving the structural information between the nodes in the graph. However, this is sub-optimal due to: (i) traditional methods have limited model capacity which limits the learning performance; (ii) existing techniques typically rely on unsupervised learning strategies and fail to couple with the latest learning paradigms; (iii) representation learning and downstream tasks are dependent on each other which should be jointly enhanced. With the remarkable success of deep learning, deep graph representation learning has shown great potential and advantages over shallow (traditional) methods, there exist a large number of deep graph representation learning techniques have been proposed in the past decade, especially graph neural networks. In this survey, we conduct a comprehensive survey on current deep graph representation learning algorithms by proposing a new taxonomy of existing state-of-the-art literature. Specifically, we systematically summarize the essential components of graph representation learning and categorize existing approaches by the ways of graph neural network architectures and the most recent advanced learning paradigms. Moreover, this survey also provides the practical and promising applications of deep graph representation learning. Last but not least, we state new perspectives and suggest challenging directions which deserve further investigations in the future.

Hypoxia-activated ADCC-enhanced humanized anti-CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity.

Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on-target off-tumor toxicity limits Ab-based therapeutics. Cluster of differentiation 147 (CD147) is a tumor-associated membrane antigen overexpressed in cancer cells. Ab-based drugs targeting CD147 have achieved inadequate clinical benefits for liver cancer due to side effects. Here, by using glycoengineering and hypoxia-activation strategies, we developed a conditional Ab-dependent cellular cytotoxicity (ADCC)-enhanced humanized anti-CD147 Ab, HcHAb18-azo-PEG5000 (HAP18). Afucosylated ADCC-enhanced HcHAb18 Ab was produced by a fed-batch cell culture system. Azobenzene (Azo)-linked PEG5000 conjugation endowed HAP18 Ab with features of hypoxia-responsive delivery and selective targeting. HAP18 Ab potently inhibits the migration, invasion, and matrix metalloproteinase secretion, triggers the cytotoxicity and apoptosis of cancer cells, and induces ADCC, complement-dependent cytotoxicity, and Ab-dependent cellular phagocytosis under hypoxia. In xenograft mouse models, HAP18 Ab selectively targets hypoxic liver cancer tissues but not normal organs or tissues, and has potent tumor-inhibiting effects. HAP18 Ab caused negligible side effects and exhibited superior pharmacokinetics compared to those of parent HcHAb18 Ab. The hypoxia-activated ADCC-enhanced humanized HAP18 Ab safely confers therapeutic efficacy against liver cancer with improved selectivity. This study highlights that hypoxia activation is a promising strategy for improving the tumor targeting potential of anti-CD147 Ab drugs.

Hypoxia-activated selectivity-improved anti-PKM2 antibody combined with prodrug TH-302 for potentiated targeting therapy in hepatocellular carcinoma.

Background: Hypoxia induces hepatocellular carcinoma (HCC) malignancies; yet it also offers treatment opportunities, exemplified by developing hypoxia-activated prodrugs (HAPs). Although HAP TH-302 combined with therapeutic antibody (Ab) has synergistic effects, the clinical benefits are limited by the on-target off-tumor toxicity of Ab. Here, we sought to develop a hypoxia-activated anti-M2 splice isoform of pyruvate kinase (PKM2) Ab combined with TH-302 for potentiated targeting therapy. Methods: Codon-optimized and hypoxia-activation strategies were used to develop H103 Ab-azo-PEG5k (HAP103) Ab. Hypoxia-activated HAP103 Ab was characterized, and hypoxia-dependent antitumor and immune activities were evaluated. Selective imaging and targeting therapy with HAP103 Ab were assessed in HCC-xenografted mouse models. Targeting selectivity, systemic toxicity, and synergistic therapeutic efficacy of HAP103 Ab with TH-302 were evaluated. Results: Human full-length H103 Ab was produced in a large-scale bioreactor. Azobenzene (azo)-linked PEG5k conjugation endowed HAP103 Ab with hypoxia-activated targeting features. Conditional HAP103 Ab effectively inhibited HCC cell growth, enhanced apoptosis, and induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) functions. Analysis of HCC-xenografted mouse models showed that HAP103 Ab selectively targeted hypoxic HCC tissues and induced potent tumor-inhibitory activity either alone or in combination with TH-302. Besides the synergistic effects, HAP103 Ab had negligible side effects when compared to parent H103 Ab. Conclusion: The hypoxia-activated anti-PKM2 Ab safely confers a strong inhibitory effect on HCC with improved selectivity. This provides a promising strategy to overcome the on-target off-tumor toxicity of Ab therapeutics; and highlights an advanced approach to precisely kill HCC in combination with HAP TH-302.