Covalent Organic Framework Ionomer Steering the CO2 Electroreduction Pathway on Cu at Industrial-Grade Current Density.

CO2 electroreduction holds great promise for addressing global energy and sustainability challenges. Copper (Cu) shows great potential for effective conversion of CO2 toward specific value-added and/or high-energy-density products. However, its limitation lies in relatively low product selectivity. Herein, we present that the CO2 reduction reaction (CO2RR) pathway on commercially available Cu can be rationally steered by modulating the microenvironment in the vicinity of the Cu surface with two-dimensional sulfonated covalent organic framework nanosheet (COF-NS)-based ionomers. Specifically, the selectivity toward methane (CH4) can be enhanced to more than 60% with the total current density up to 500 mA cm-2 in flow cells in both acidic (pH = 2) and alkaline (pH = 14) electrolytes. The COF-NS, characterized by abundant apertures, can promote the accumulation of CO2 and K+ near the catalyst surface, alter the adsorption energy and surface coverage of *CO, facilitate the dissociation of H2O, and finally modulate the reaction pathway for the CO2RR. Our approach demonstrates the rational modulation of reaction interfaces for the CO2RR utilizing porous open framework ionomers, showcasing their potential practical applications.

Event-Triggered Finite-Time Formation Control of Underactuated Multiple ASVs with Prescribed Performance and Collision Avoidance.

In this paper, an event-triggered finite-time controller is proposed for solving the formation control problems of underactuated multiple autonomous surface vessels (ASVs), including asymmetric mass matrix, collision avoidance, maintaining communication distances and prescribed performance. First, to not only avoid collisions between the follower and leader but also maintain an effective communication distance, a desired tracking distance is designed to be maintained. Second, an improved barrier Lyapunov function (BLF) is proposed to implement the tracking error constraint. In addition, the relative threshold event-triggering strategy effectively solves the communication pressure problem and greatly saves communication resources. Finally, based on coordinate transformation, line of sight (LOS) and dynamic surface control (DSC), a comprehensive finite-time formation control method is proposed to avoid collisions and maintain communication distance. All the signals of the proposed control system can be stabilized in finite time (PFS). The numerical simulation results verify the effectiveness of the proposed control system.

Efficiently accumulating germ-like stem cells from mouse postnatal ovary by in situ tissue culture.

Although recent studies have revealed that germline stem cells (GSCs) exist in the mouse postnatal ovary, how to efficiently obtain GSCs for regenerating neo-oogenesis is still a technical challenge. Here, we report that using in situ tissue culture we can efficiently accumulate large amounts of proliferating germ-like cells from mouse postnatal ovaries. Usually, more than 10,000 germ-like cells can be derived from one ovary by this method, and over 20% of these cells can grow into germ-like cells with self-renewal, which thus can serve as a good cell pool to isolate GSCs by other cell assorting methods such as FACS. This method is simple and time-saving, which should be useful for in future studies on mouse GSCs.

Pathogenic characteristics of a QX-like infectious bronchitis virus strain SD in chickens exposed at different ages and protective efficacy of combining live homologous and heterologous vaccination.

Continued reports of infections with infectious bronchitis virus (IBV) variants have occurred since its first isolation in the 1930s. Currently, QX-like IBVs are the predominant circulating genotype around the world. Here, the pathogenicity of QX-like IBV strain SD was characterized in chickens at different ages of exposure to the virus, and the protection efficacy of available vaccine combinations against IBV was evaluated. The results revealed that QX-like IBV strain SD was severely pathogenic in chickens, causing respiratory, urinary and reproductive infections, irrespective of age, based on clinical observations, viral distribution in tissues and a ciliostasis study. Severe respiratory signs, tracheal cilia injury, nephritis and abnormal development of the oviduct and ovarian follicles were evident throughout the experiment. A challenge experiment demonstrated that the homologous QX vaccine showed superior protection efficacy compared with other available vaccines, confirming the importance of IBV vaccine seed homology against the circulating IBV strains. Our findings aid an understanding of the pathogenicity of QX-like IBVs that may help to further control the infection.

Cytokine expression in chicken embryo fibroblasts in response to infection with virulent or lentogenic avian avulavirus 1 (AAvV-1).

To investigate cytokine expression in chicken embryo fibroblast (CEF) cells, a virulent avian avulavirus 1 (AAvV-1) strain called SG10 that rapidly causes 100% mortality in its host, and a vaccine strain (La Sota) were characterized. Real-time quantitative PCR was performed on RNA samples from CEF cells, which were collected at 0, 24, 48 and 72 h post-infection. The dynamic expression patterns of ten cytokines (TNF-α, IFN-α, IFN-ß, IL-1ß, IL-2, IL-6, IL-10, IL-13, IL-15 and IL-18) were investigated. The results showed that infection with lentogenic La Sota induced significantly higher levels of the antiviral cytokines IFN-α and IFN-ß, proinflammatory cytokines IL-2, IL-15 and IL-18, and the anti-inflammatory cytokine IL-10, than did infection with virulent SG10. Furthermore, the SG10 strain induced dramatically higher levels of the inflammatory cytokine IL-6 than those observed in cells infected with La Sota. However, the expression patterns of the other cytokines that were tested did not show any obvious trends or statistically significant differences between cells infected with the virulent and avirulent strains. These data show that infection with lentogenic La Sota induced more effective immune responses and anti-viral effects than did infection with virulent SG10 in CEFs. Our data provide distinct expression patterns of IFNs and proinflammatory and anti-inflammatory cytokines to AAvV-1 by virulence in CEF cells.

Geniposide protects against ox-LDL-induced foam cell formation through inhibition of MAPKs and NF-kB signaling pathways.

Atherosclerosis (AS) is characterized by the significant accumulation of low-density lipoprotein (LDL)-cholesterol in macrophages that reside in the vessel wall and the resultant inflammatory response. Therefore, inhibition of LDL-induced inflammation is a promising interference for AS. Many traditional Chinese medicine prescriptions have been developed for AS treatment. Geniposide (GEN) is an iridoid glycoside mainly found in Gardenia jasminoides fruit. Although GEN has previously been shown to possess anti-atherosclerotic activities, its effects on the formation of macrophage-derived foam cells remain poorly characterized. In our current study, we demonstrated that GEN could significantly inhibit oxidized light-density lipoprotein (ox-LDL) induced macrophage foam cell formation and the expression of pro-inflammatory cytokines in a dose-dependent manner. In addition, treatment of GEN in bone-marrow derived macrophages repressed iNOS expression and NO expression. GEN could also alleviate ox-LDL-dependent up-regulation of CD36 expression by blocking the phosphorylation of p38 MAPK, ERK, JNK and NF-kB p65. The results of our current study demonstrate that GEN exhibits significant therapeutic effects against ox-LDA-induced foam cell formation and inflammation. Therefore, GEN is promising agent for treating AS.

Current status of the treatment of blood blister-like aneurysms of the supraclinoid internal carotid artery: A review.

Currently, the treatment of blood blister-like aneurysms (BBAs) of the supraclinoid internal carotid artery (ICA) is challenging and utilizes many therapeutic methods, including direct clipping and suturing, clipping after wrapping, clipping after suturing, coil embolization, stent-assisted coil embolization, multiple overlapping stents, flow-diverting stents, covered stents, and trapping with or without bypass. In these therapeutic approaches, the optimal treatment method for BBAs has not yet been defined based on the current understanding of BBAs of the supraclinoid ICA. Therefore, in this study, we aimed to review the literature from PubMed to discuss and analyze the pros and cons of the above approaches while adding our own viewpoints to the discussion. Among the surgical methods, direct clipping was the easiest method if the compensation of the collateral circulation of the intracranial distal ICA was sufficient or direct clipping did not induce stenosis in the parent artery. In addition, the clipping after wrapping technique should be chosen as the optimal surgical modality to prevent rebleeding from these lesions. Among the endovascular methods, multiple overlapping stents (≥3) with coils may be a feasible alternative for the treatment of ruptured BBAs. In addition, flow-diverting stents appear to have a higher rate of complete occlusion and a lower rate of retreatment and are a promising treatment method. Finally, when all treatments failed or the compensation of the collateral circulation of the intracranial distal ICA was insufficient, the extracranial-intracranial (EC-IC) arterial bypass associated with surgical or endovascular trapping, a complex and highly dangerous method, was used as the treatment of last resort.

Assisted Reproduction Causes Reduced Fetal Growth Associated with Downregulation of Paternally Expressed Imprinted Genes That Enhance Fetal Growth in Mice.

Alteration of intrauterine growth trajectory is linked to metabolic diseases in adulthood. In mammalian and, specifically, human species, pregnancies through assisted reproductive technology (ART) are associated with changes in intrauterine growth trajectory. However, it is still unclear how ART alters intrauterine growth trajectory, especially reduced fetal growth in early to midgestation. In this study, using a mouse model, it was found that ART procedures reduce fetal and placental growth at Embryonic Day 10.5. Furthermore, ART leads to decreased methylation levels at H19, KvDMR1, and Snrpn imprinting control regions in the placentae, instead of fetuses. Furthermore, in the placenta, ART downregulated a majority of parentally expressed imprinted genes, which enhance fetal growth, whereas it upregulated a majority of maternally expressed genes which repress fetal growth. Additionally, the expression of genes that regulate placental development was also affected by ART. ART also downregulated a majority of placental nutrient transporters. Disruption of genomic imprinting and abnormal expression of developmentally and functionally relevant genes in placenta may influence the placental development and function, which affect fetal growth and reprogramming.

Use of Transcranial Doppler Ultrasound for Diagnosis of Brain Death in Patients with Severe Cerebral Injury.

BACKGROUND The aim of this study was to investigate the use of transcranial Doppler (TCD) for diagnosis of brain death in patients with severe cerebral injury. MATERIAL AND METHODS This retrospective study enrolled 42 patients based on inclusion and exclusion criteria. All patients were divided into either the brain death group or the survival group according to prognosis. Blood flow of the brain was examined by TCD and analyzed for spectrum changes. The average blood flow velocity (Vm), pulse index (PI), and diastolic blood flow in reverse (RDF) were recorded and compared. RESULTS The data demonstrated that the average speed of bilateral middle cerebral artery blood flow in the brain death group was significantly reduced (P<0.05). However, the PI of the brain death group increased significantly. Moreover, RDF spectrum and nail-like sharp peak spectrum of the brain death group was higher than in the survival group. CONCLUSIONS Due to its simplicity, high repeatability, and specificity, TCD combined with other methods is highly valuable for diagnosis of brain death in patients with severe brain injury.

Sensitization to beer ingredients in Chinese individuals with beer allergy: a clinical study of 20 cases.

BACKGROUND: Rare case reports of allergic reactions to beer have been published, but the nature of the eliciting substances in beer ingredients is often unknown. OBJECTIVE: It was the aim of this study to identify sensitization patterns against various beer ingredients in Chinese individuals with beer allergy. METHODS: Twenty-seven Chinese individuals with a clear-cut history of beer allergy were prescreened to answer a specific questionnaire related to the history and symptoms of beer allergy. Twenty individuals underwent allergy diagnostics with different food allergens and extracts of beer ingredients using the skin prick test (SPT) and the open oral provocation test (OPT) with beer. RESULTS: Fifteen patients (75%) showed positive reactions to one or more beer ingredients. Of these, 9 individuals, reactive to sorghum and/or sorghum malt also showed positive reactions to other ingredients. Seventeen individuals showed variable symptoms after the OPT. Cutaneous erythema and urticaria were the most common symptoms and usually persisted for over 2 h. There were no significant differences in SPT reactivity to beer ingredients between male and female individuals. Single patients reacted to barley, hops or yeast. CONCLUSIONS: Sensitization to sorghum and/or sorghum malt was the most common finding in Chinese individuals with beer allergy.

Significance of combined detection of LunX mRNA and tumor markers in diagnosis of lung carcinoma.

OBJECTIVE: To evaluate the significance of combined detection of LunX mRNA, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 21-1 fragment (CYFRA21-1) in clinical diagnosis of lung carcinoma. METHODS: Based on the quantitative RT-PCR and chemiluminescence immunoassay, the expression levels of LunX mRNA, CEA, NSE, and CYFRA21-1 in 113 patients with lung carcinoma (case group) and 30 healthy participants (control group) were detected. Meantime, the sensitivity, specificity, and accuracy of the combination detection were also explored. RESULTS: The positive rates of LunX mRNA in peripheral blood and CEA, NSE, and CYFRA21-1 in serum were significantly higher in case group than those in control group ((χ) (2)=17.295, 16.825, 19.148, and 17.450; P<0.05). There was no statistical significance when positive rate of LunX mRNA was evaluated among different pathological types ((χ) (2)=0.047, P>0.05). The positive rate of LunX mRNA in stage I + II, III, and IV had a significantly increasing tendency ((χ) (2)=10.565, 32.462, P<0.05). The positive rate of CYFRA21-1 was highest in squamous carcinoma (78.5%), the positive rate of NSE was highest in small cell carcinoma (86.7%), and the positive rate of CEA wag highest in lung adenocarcinoma (80.4%). The sensitivity and accuracy of the combination detection were 91.1% and 88.1%, respectively. CONCLUSIONS: The combined detection of LunX mRNA and tumor markers (TMs) including CEA, NSE, and CYFRA21-1 in peripheral blood is helpful to increase the diagnostic accuracy of lung cancer. Also, it can inform the pathological typing of lung carcinoma.

Guiding vector field and self-structuring learning network-based formation control of underactuated surface vessels in static obstacle environments with flexible performances.

To address the problem of underactuated surface vessel (USV) formation control in static obstacle environments with model uncertainties and time-varying external disturbances, a model-free formation control strategy is proposed in this paper. First, based on the guiding vector field (GVF), a composite GVF is developed to guide USV formation to the desired position and to avoid multiple static obstacles. Second, a flexible constraint strategy is introduced, and the constraint boundary conditions are appropriately relaxed to avoid singularities in the obstacle environment. Then, based on the Mexican hat wavelet function, the self-structuring fuzzy Mexican hat wavelet cerebellar model articulation controller (SCMAC), and a self-structuring fuzzy Mexican hat wavelet brain emotional learning controller (SBELC), are proposed to achieve model-free control. In addition, the self-structuring algorithm is embedded into SCMAC and SBELC to achieve autonomous optimization of the controller structure and to reduce the computational effort of the control system. The salient features in the proposed control strategy are as follows. First, the proposed model-free formation control strategy does not have to rely on accurate model information. Second, collisions are effectively avoided, and good control performance is guaranteed even under the influence of disturbances and static obstacles. Third, the proposed self-structuring algorithm achieves automatic construction of the controller structure. Finally, the signals in the control system are proven to be bounded, and the simulation results verify the feasibility and superiority of the proposed model-free control strategy.

The Kunming mouse: as a model for age-related decline in female fertility in human.

To ascertain whether the Kunming (KM) mouse is an available model for age-related decline in female fertility in human or not, oocytes from young (6-8 weeks), middle-aged (9 months) and aged (12 months) female mice were compared with respect to number of oocytes, frequency of in-vitro maturation (IVM) and in-vitro fertilization (IVF), and meiotic chromosome segregation and alignment. The mean number of pups born per mouse decreased significantly from the young to the middle-aged and the aged mice. The mean number of ovarian follicles, ovarian germinal vesicle oocytes and ovulated MII oocytes decreased significantly with maternal age. The rate of IVM in oocytes from young mice (73.9%) was less significantly than that in oocytes from middle-aged and aged mice (86.1% and 84.4%, respectively). Immunocytochemical analysis showed that ageing caused a significantly higher rate (49.3%) of chromosome misalignment than that (15.7%) of the young mice. The presence of premature chromatids was also significantly higher in MII oocytes of aged mice as compared with young mice (37.8 versus 8.3%). Pronuclear formation was delayed in oocytes of middle-aged and aged females (35.5 and 42.3% respectively in 5 h of IVF) as compared with young mice (88.1%). The study suggests that KM mouse exhibits an age-related decline in female fertility. Significant reduction of germinal vesicle (GV) and MII oocytes and significant increase of metaphase chromosome misalignment and premature chromatid segregation after meiotic maturation of oocytes, similar to human, presumably contribute to the decline in aged KM mice.

G9a co-localized with histone H3 lysine 9 monomethylation but not dimethylation in a nuclear membrane-dependent manner during mouse preimplantation embryo development.

PURPOSE: Histone H3 lysine 9 (H3K9) methylation plays an important role in the regulation of preimplantation embryo development. G9a has been reported to be a major H3K9mono (m1)/dimethylation(m2) methyltransferase and to contain nuclear localization signals. This study was performed to investigate the correlation between H3K9 methylation level and G9a localization when the nuclear membrane undergoes periodic reconstruction in the cell cycle during preimplantation embryo development. METHODS: The fluorescence intensity was examined via immunofluorescence. The mRNA expression of G9awas determined using real-time reverse transcriptase (RT)-PCR. Eight-cell embryos were cultured in KSOM supplemented with nocodazole (0.5 µM) for 12 h. RESULTS: In this study, it was observed that the fluorescence intensity of H3K9m2 and G9a began to increase significantly from the 4-cell stage and reached the peak at the morula stage (p < 0.001), but the fluorescence intensity declined to 4-cell-stage levels when it reached the blastula stage. We observed a similar pattern when we examined G9a mRNA expression. Once the nuclear membrane disintegrated, G9a and H3K9m1 were not detectable by immunofluorescence; when it was reconstructed, G9a and H3K9m1 had relocated to the cell nucleus. However, no significant change was observed in the H3K9m2 localization or in the G9a mRNA level (p > 0.05) during the whole process. JHDM2A was consistently localized in the cytoplasm irrespective of the presence or absence of a nuclear membrane. CONCLUSION: These results indicate dynamic changes in the expression level of H3K9m2 and G9a as preimplantation embryogenesis progresses. G9a co-localized with H3K9 m1 in a nuclear membrane-dependent manner during mouse preimplantation embryo development.

Causal Association Between Tea Consumption and Gout: A Mendelian Randomization Study.

OBJECTIVE: Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited. We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomization (MR). METHODS: Genome-wide association studies in UK Biobank included 349 376 individuals and successfully discovered single-nucleotide polymorphisms linked to consumption of one cup of tea per day. Summary statistics from the Chronic Kidney Disease Genetics consortium included 13 179 cases and 750 634 controls for gout. Two-sample MR analyses were used to evaluate the relationship between tea consumption and gout risk. The inverse-variance weighted (IVW) method was used for primary analysis, and sensitivity analyses were also conducted to validate the potential causal effect. RESULTS: In this study, the genetically predicted increase in tea consumption per cup was associated with a lower risk of gout in the IVW method (OR: 0.90; 95% CI: 0.82-0.98). Similar results were found in weighted median methods (OR: 0.88; 95% CI: 0.78-1.00), while no significant associations were found in MR-Egger (OR: 0.89; 95% CI: 0.71-1.11), weighted mode (OR: 0.80; 95% CI: 0.65-0.99), and simple mode (OR: 1.01; 95% CI: 0.75-1.36). In addition, no evidence of pleiotropy was detected by MR-Egger regression (P=0.95) or MR-PRESSO analysis (P=0.07). CONCLUSION: This study provides evidence for the daily consumption of an extra cup of tea to reduce the risk of gout.

Corrigendum: Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132.

[This corrects the article DOI: 10.3389/fonc.2022.951589.].

Increased cleavage rate of human nuclear transfer embryos after 5-aza-2'-deoxycytidine treatment.

As an abundant source that involves fewer ethical considerations, human abnormally fertilized zygotes are superior to oocytes as therapeutic cloning recipients of nuclear transfer. However, more effective manipulation conditions should be developed for somatic cell nuclear transfer (SCNT) studies using human abnormally fertilized zygotes as recipients. The present study found that the use of cytochalasin B was not necessary for, and even harmful to, the enucleation of human zygotes. This study also decreased the DNA methylation levels in reconstructed embryos using a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), in an attempt to correct the abnormalities in DNA methylation that might play an important role in the failure of embryo development. After 5-aza-dC treatment and nuclear transfer (NT-Aza group), 32.7% of reconstructed embryos developed to the 8-cell stage, which is a much higher percentage than that of the nuclear transfer only (NT) group (11.1%). The DNA methylation level in the NT-Aza group was significantly lower than that of the NT group, as determined by 5-methylcytosine immunodetection. Based on the present results, this study recommends performing the enucleation procedure without cytochalasin B treatment and using 5-aza-dC in the culture of reconstructed embryos in human SCNT studies.

Effect of age, GV transfer and modified nucleocytoplasmic ratio on PKCα in mouse oocytes and early embryos.

Protein kinase C (PKC) is a family of Ser/Thr protein kinases that can be activated by Ca2+, phospholipid and diacylglycerol. There is evidence that PKC plays key roles in the meiotic maturation and activation of mammalian oocytes. The present study aimed to monitor the effect of age, germinal vesicle (GV) transfer and modified nucleoplasmic ratio on the subcellular distribution profile of PKCα, an important isozyme of PKC, in mouse oocytes undergoing meiotic maturation and following egg activation. Germinal vesicle oocytes were collected from 6-8-week-old and 12-month-old mice. Germinal vesicle-reconstructed oocytes and GV oocytes with one-half or one-third of the original oocyte volume were created using micromanipulation and electrofusion. The subcellular localization of PKCα was detected by immunocytochemistry and laser confocal microscopy. Our study showed that PKCα had a similar location pattern in oocytes and early embryos from young and old mice. PKCα was localized evenly in ooplasm, with weak staining in GV at the GV stage, and present in the entire meiosis II (MII) spindle at the MII stage. In pronuclear and 2-cell embryos, PKCα was concentrated in the nucleus except for the nucleolus. After the GV oocytes were reconstructed, the resultant MII oocytes and embryos showed a similar distribution of PKCα between reconstructed and unreconstructed controls. After one-half or two-thirds of the cytoplasm was removed from the GV oocytes, PKCα still had a similar location pattern in MII oocytes and early embryos from the GV oocytes with modified nucleoplasmic ratio. Our study showed that age, GV transfer and modified nucleocytoplasmic ratio does not affect distribution of PKCα during mouse oocyte maturation, activation, and early embryonic mitosis.

Development and validation of a survival prediction model for patients received mechanical ventilation in the intensive care unit: a large sample size cohort from the MIMIC database.

BACKGROUND: Mechanical ventilation remains one of the primary management measures for critically ill patients in intensive care units (ICUs). However, previous studies on the prognosis prediction of ICU patients received mechanical ventilation were limited. This study was to develop and validate a nomogram for predicting short- and long-term survival among patients who received mechanical ventilation in the ICU. METHODS: This was a retrospective cohort study with a 3-year follow-up. Demographic, laboratory, clinical data of 16,775 participants aged ≥18 years who received mechanical ventilation in the ICU were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The outcomes of this study were 1-month, 3-month, 1-year, and 3-year survival. All eligible patients were randomly classified into the training and testing groups with a ratio of 7:3. A multivariate Cox regression in the training group was used to explore the predictors and develop the predictive nomogram. Internal and subgroup validations were performed, and the C-index was calculated to estimate the predictive performance of the nomogram. The time-dependent receiver operating characteristic curves were drawn, and corresponding areas under the curve (AUC) were calculated. RESULTS: Totally 6,291 patients died during the follow-up duration. Age, gender, ethnicity, ICU type, comorbidity, days of mechanical ventilation, white blood cell count, blood urea nitrogen, the fraction of inspiration O2, Sequential Organ Failure Assessment scores, and the Glasgow coma score were predictors of the survival of ICU patients who received mechanical ventilation (P<0.05). The C-index of the nomogram was 0.819 and was validated in the testing group at 0.816. The AUCs for the prognostic nomogram for 1-month, 3-month, 1-year, and 3-year survival were 0.889, 0.892, 0.882, and 0.866, respectively. CONCLUSIONS: This nomogram showed good predictive performance for short- and long-term survival in ICU patients treated with mechanical ventilation, which may be a useful tool for clinicians to assess the prognosis of patients and to adjust treatment strategies in time.

Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132.

Purpose: The aim of this study was to improve the intratumoral accumulation of an antibody-drug conjugate (ADC) and minimize its off-target toxicity, SKB264, a novel anti-trophoblast antigen 2 (TROP2) ADC that was developed using 2-methylsulfonyl pyrimidine as the linker to conjugate its payload (KL610023), a belotecan-derivative topoisomerase I inhibitor. The preclinical pharmacologic profiles of SKB264 were assessed in this study. Methods: The in vitro and in vivo pharmacologic profiles of SKB264, including efficacy, pharmacokinetics-pharmacodynamics (PK-PD), safety, and tissue distribution, were investigated using TROP2-positive cell lines, cell-derived xenograft (CDX), patient-derived xenograft (PDX) models, and cynomolgus monkeys. Moreover, some profiles were compared with IMMU-132. Results: In vitro, SKB264 and SKB264 monoclonal antibody (mAb) had similar internalization abilities and binding affinities to TROP2. After cellular internalization, KL610023 was released and inhibited tumor cell survival. In vivo, SKB264 significantly inhibited tumor growth in a dose-dependent manner in both CDX and PDX models. After SKB264 administration, the serum or plasma concentration/exposure of SKB264 (conjugated ADC, number of payload units ≥1), total antibody (Tab, unconjugated and conjugated mAb regardless of the number of the payload units), and KL610023 in cynomolgus monkeys increased proportionally with increasing dosage from 1 to 10 mg/kg. The linker stability of SKB264 was significantly enhanced as shown by prolonged payload half-life in vivo (SKB264 vs. IMMU-132, 56.3 h vs. 15.5 h). At the same dose, SKB264's exposure in tumor tissue was 4.6-fold higher than that of IMMU-132. Conclusions: Compared with IMMU-132, the longer half-life of SKB264 had a stronger targeting effect and better antitumor activity, suggesting the better therapeutic potential of SKB264 for treating TROP2-positive tumors.