Rapid, sensitive, and visual detection of pseudorabies virus with an RPA-CRISPR/EsCas13d-based dual-readout portable platform.

Pseudorabies viruses (PRV) pose a major threat to the global pig industry and public health. Rapid, intuitive, affordable, and accurate diagnostic testing is critical for controlling and eradicating infectious diseases. In this study, a portable detection platform based on RPA-CRISPR/EsCas13d was developed. The platform exhibits high sensitivity (1 copy/µL), good specificity, and no cross-reactivity with common pathogens. The platform uses rapid preamplification technology to provide visualization results (lateral flow assays or visual fluorescence) within 1 h. Fifty pig samples (including tissues, oral fluids, and serum) were tested using this platform and real-time quantitative polymerase chain reaction (qPCR), showing 34.0 % (17 of 50) PRV positivity with the portable CRISPR/EsCas13d dual-readout platform, consistent with the qPCR results. These results highlight the stability, sensitivity, efficiency, and low equipment requirements of the portable platform. Additionally, a novel point-of-care test is being developed for clinical use in remote rural and resource-limited areas, which could be a prospective measure for monitoring the progression of pseudorabies and other infectious diseases worldwide.

Porcine reproductive and respiratory syndrome virus infects the reproductive system of male piglets and impairs development of the blood-testis barrier.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease that threatens the global swine industry. Recent studies have focused on the damage that PRRSV causes to the reproductive system of male pigs, although pathological research is lacking. Therefore, we examined the pathogenic mechanisms in male piglets infected with PRRSV. Gross and histopathological changes indicated that PRRSV affected the entire reproductive system, as confirmed via immunohistochemical analysis. PRRSV infected Sertoli cells and spermatogonia. To test the new hypothesis that PRRSV infection in piglets impairs blood - testis barrier (BTB) development, we investigated the pathology of PRRSV damage in the BTB. PRRSV infection significantly decreased the quantity and proliferative capacity of Sertoli cells constituting the BTB. Zonula occludens-1 and ß-catenin were downregulated in cell - cell junctions. Transcriptome analysis revealed that several crucial genes and signalling pathways involved in the growth and development of Leydig cells, Sertoli cells, and tight junctions in the testes were downregulated. Apoptosis, necroptosis, inflammatory, and oxidative stress-related pathways were activated, whereas hormone secretion-related pathways were inhibited. Many Sertoli cells and spermatogonia underwent apoptosis during early differentiation. Infected piglets exhibited disrupted androgen secretion, leading to significantly reduced testosterone and anti-Müllerian hormone levels. A cytokine storm occurred, notably upregulating cytokines such as tumour necrosis factor-α and interleukin-6. Markers of oxidative-stress damage (i.e. H2O2, malondialdehyde, and glutathione) were upregulated, whereas antioxidant-enzyme activities (i.e. superoxide dismutase, total antioxidant capacity, and catalase) were downregulated. Our results demonstrated that PRRSV infected multiple organs in the male reproductive system, which impaired growth in the BTB.

Rapid, sensitive, and visual detection of swine Japanese encephalitis virus with a one-pot RPA-CRISPR/EsCas13d-based dual readout portable platform.

Japanese encephalitis (JE), a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV), poses a serious threat to global public health. The low viremia levels typical in JEV infections make RNA detection challenging, necessitating early and rapid diagnostic methods for effective control and prevention. This study introduces a novel one-pot detection method that combines recombinant enzyme polymerase isothermal amplification (RPA) with CRISPR/EsCas13d targeting, providing visual fluorescence and lateral flow assay (LFA) results. Our portable one-pot RPA-EsCas13d platform can detect as few as two copies of JEV nucleic acid within 1 h, without cross-reactivity with other pathogens. Validation against clinical samples showed 100 % concordance with real-time PCR results, underscoring the method's simplicity, sensitivity, and specificity. This efficacy confirms the platform's suitability as a novel point-of-care testing (POCT) solution for detecting and monitoring the JE virus in clinical and vector samples, especially valuable in remote and resource-limited settings.

Application of digital impression and model in removable partial dentures for Kennedy classâ andâ ¡dentition defects.

OBJECTIVES: This study aimed to evaluate the application of digital impression and resin model technology in removable partial dentures (RPD) for Kennedy classⅠandⅡdentition defects. METHODS: Patients with Kennedy classⅠorⅡdental defect were selected and grouped in accordance with the following denture production processes: digital impression/resin model/cast cobalt-chromium alloy framework group (group A), digital impression/resin model/laser printed titanium framework group (group B), alginate impression/plaster model/cast cobalt-chromium alloy framework group (group C), and alginate impression/plaster model/laser printed titanium framework group (group D), with 40 cases in each group. The final RPD was examined in place in the mouth, and the evaluation indicators included the retention force of clamp ring, the tightness of connector and base, and the accuracy of occlusion. The evaluation scores of each index were used for analysis on the Kruskal-Wallis rank-sum test. RESULTS: No statistically significant difference in the score of each index was found among the four groups in RPD. CONCLUSIONS: The cast cobalt-chromium alloy and laser-printed titanium framework RPD using digital impression and resin model can meet the clinical restoration requirements of patients with Kennedy classⅠandⅡdentition defects.

Transcriptomic and metabolomic insights into the antimony stress response of tall fescue (Festuca arundinacea).

Antimony (Sb) is a toxic heavy metal that severely inhibits plant growth and development and threatens human health. Tall fescue, one of the most widely used grasses, has been reported to tolerate heavy metal stress. However, the adaptive mechanisms of Sb stress in tall fescue remain largely unknown. In this study, transcriptomic and metabolomic techniques were applied to elucidate the molecular mechanism of the Sb stress response in tall fescue. These results showed that the defense process in tall fescue was rapidly triggered during the early stages of Sb stress. Sb stress had toxic effects on tall fescue, and the cell wall and voltage-gated channels are crucial for regulating Sb permeation into the cells. In addition, the pathway of glycine, serine and threonine metabolism may play key roles in the Sb stress response of tall fescue. Genes such as ALDH7A1 and AGXT2 and metabolites such as aspartic acid, pyruvic acid, and biuret, which are related to biological processes and pathways, were key genes and compounds in the Sb stress response of tall fescue. Therefore, the regulatory mechanisms of specific genes and pathways should be investigated further to improve Sb stress tolerance.

Antimony isotopic fractionation induced by Sb(V) adsorption on ß-MnO2.

Antimony (Sb) isotopes hold immense promise for unraveling Sb biogeochemical cycling in environmental systems. Mn oxides help control the fate of Sb via adsorption reactions, yet the behavior and mechanisms of Sb isotopic fractionation on Mn oxides are poorly understood. In this study, we examine the Sb isotopic fractionation induced by adsorption on ß-MnO2 in different experiments (kinetic, isothermal, effect of pH). We observe that adsorption on ß-MnO2 surfaces preferentially enriches lighter Sb isotopes through equilibrium fractionation, with Δ123Sbaqueous-adsorbed of 0.55-0.79 ‰. Neither the pH or surface coverage affects the fractionation magnitude. The analysis of extended X-ray absorption fine structure (EXAFS) demonstrates that the enrichment of light isotope results from the adsorption of inner-sphere complexation on solids. Our finding of this study enhances our comprehension of the impact of ß-MnO2 on Sb isotopic fractionation behavior and mechanism and facilitate the applicability of Sb isotopes as effective tracers to elucidate the origins and pathways of Sb contamination in environmental systems, as well as provide a new insight into forecasting the isotopic fractionation of other similar metals adsorbed by manganese oxides.

Two 2D Metal-Organic Frameworks Based on Purine Carboxylic Acid Ligands for Photocatalytic Oxidation of Sulfides and CO2 Chemical Fixation.

Two two-dimensional (2D) layered metal-organic frameworks (MOFs), namely, {[Yb(L)(H2O)2NO3]·2H2O}n (Yb-MOF) and [Er(L)(H2O)3Cl]n (Er-MOF) (H2L = 5-((6H-purin-6-yl)amino)isophthalic acid), were constructed by a solvothermal method and characterized. The catalytic performance study showed that the Yb-MOF could efficiently catalyze the oxidation of sulfides to sulfoxides under 15 W light-emitting diode (LED) blue light irradiation. Electron paramagnetic resonance spectroscopy and free-radical trapping experiments demonstrated that the photocatalytic reaction process involved •O2-, and the corresponding mechanism was proposed. Moreover, Er-MOF exhibited good catalytic efficiency and excellent substrate tolerance in the cycloaddition reaction of CO2, and the reaction conditions were mild. After 5 cycles, the catalytic activities of two MOFs did not significantly decrease, and the framework structures remained unchanged. Therefore, the Yb-MOF and Er-MOF were considered efficient and stable heterogeneous catalysts.

Ginsenoside modified lipid-coated perfluorocarbon nanodroplets: A novel approach to reduce complement protein adsorption and prolong in vivo circulation.

Lipid-coated perfluorocarbon nanodroplets (lp-NDs) hold great promise in bio-medicine as vehicles for drug delivery, molecular imaging and vaccine agents. However, their clinical utility is restricted by limited targeted accumulation, attributed to the innate immune system (IIS), which acts as the initial defense mechanism in humans. This study aimed to optimize lp-ND formulations to minimize non-specific clearance by the IIS. Ginsenosides (Gs), the principal components of Panax ginseng, possessing complement inhibition ability, structural similarity to cholesterol, and comparable fat solubility to phospholipids, were used as promising candidate IIS inhibitors. Two different types of ginsenoside-based lp-NDs (Gs lp-NDs) were created, and their efficacy in reducing IIS recognition was examined. The Gs lp-NDs were observed to inhibit the adsorption of C3 in the protein corona (PC) and the generation of SC5b-9. Adding Gs to lp-NDs reduced complement adsorption and phagocytosis, resulting in a longer blood circulation time in vivo compared to lp-NDs that did not contain Gs. These results suggest that Gs can act as anti-complement and anti-phagocytosis adjuvants, potentially reducing non-specific clearance by the IIS and improving lifespan.

Assembly of Functional Co(II) Metal-Organic Frameworks through a Mixed Ligand Strategy: Structure and Photocatalytic Degradation Properties.

Four Co(II)-based metal-organic frameworks (MOFs) were constructed by a mixed ligand strategy under solvothermal conditions. The controllable modification of the bridging groups in the secondary building units was realized by changing the anions in MOFs 1-3. The MOF 4 with 3D framework structure was obtained by regulating the solvent ratio following the synthesis process of MOF 3. Furthermore, the MOFs 1-4 exhibited efficient photocatalytic activity for the degradation of malachite green (MG) dye without any photosensitizer or cocatalyst under a low-energy light source, the decolorization ratio of MG all reached more than 96.0% within 60 min, and maximal degradation was obtained to be 99.4% (MOF 4). The recycling experiments showed that the degradation rate of MG was still higher than 91% after 10 cycles. In the MOF 4 as representation, the photocatalytic process was explored systematically. The possible mechanism of catalytic degradation was discussed, which proved the existence of efficient oxidation active factors (•O2-, •OH, and h+). The possible intermediates and degradation pathways were investigated based on high-performance liquid chromatography tandem mass spectrometry. Additionally, MOFs 1-4 also exhibited excellent photocatalytic activity for the degradation of methylene blue, methyl violet, rhodamine B, and basic red 9.

Comparative genomics analysis reveals sequence characteristics potentially related to host preference in Cryptosporidium xiaoi.

Cryptosporidium spp. are important diarrhea-associated pathogens in humans and livestock. Among the known species, Cryptosporidium xiaoi, which causes cryptosporidiosis in sheep and goats, was previously recognized as a genotype of the bovine-specific Cryptosporidium bovis based on their high sequence identity in the ssrRNA gene. However, the lack of genomic data has limited characterization of the genetic differences between the two closely related species. In this study, we sequenced the genomes of two C. xiaoi isolates and performed comparative genomic analysis to identify the sequence uniqueness of this ovine-adapted species compared with other Cryptosporidium spp. Our results showed that C. xiaoi is genetically related to C. bovis as shown by their 95.8% genomic identity and similar gene content. Consistent with this, both C. xiaoi and C. bovis appear to have fewer genes encoding mitochondrial metabolic enzymes and invasion-related protein families. However, they appear to possess several species-specific genes. Further analysis indicates that the sequence differences between these two Cryptosporidium spp. are mainly in 24 highly polymorphic genes, half of which are located in the subtelomeric regions. Some of these subtelomeric genes encode secretory proteins that have undergone positive selection. In addition, the genomes of two C. xiaoi isolates, identified as subtypes XXIIIf and XXIIIh, share 99.9% nucleotide sequence identity, with six highly divergent genes encoding putative secretory proteins. Therefore, these species-specific genes and sequence polymorphism in subtelomeric genes probably contribute to the different host preference of C. xiaoi and C. bovis.

Conjugated Network Supporting Highly Surface-Exposed Ru Site-Based Artificial Antioxidase for Efficiently Modulating Microenvironment and Alleviating Solar Dermatitis.

Solar dermatitis, a form of acute radiation burn that affects the skin, results from overexposure to ultraviolet B (UVB) radiation in strong sunlight. Cell damage caused by the accumulation of reactive oxygen species (ROS) produced by UVB radiation plays an important role in UVB-induced inflammation in the skin. Here, for efficiently scavenging excess ROS, modulating the microenvironment, and alleviating solar dermatitis, a π-conjugated network polyphthalocyanine supporting a highly surface-exposed Ru active site-based artificial antioxidase (HSE-PPcRu) is designed and fabricated with excellent ROS-scavenging, antioxidant, and anti-inflammatory capabilities. In photodamaged human keratinocyte cells, HSE-PPcRu could modulate mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B signaling pathways, prevent DNA damage, suppress apoptosis, inhibit pro-inflammatory cytokine secretion, and alleviate cell damage. In vivo animal experiments reveal the higher antioxidant and anti-inflammatory efficacies of HSE-PPcRu by reversing the activation of p38 and c-Jun N-terminal kinase, inhibiting expression of cyclooxygenase-2, interleukin-6, interleukin-8, and tumor necrosis factor-α. This work not only provides an idea for alleviating solar dermatitis via catalytically scavenging ROS and modulating the microenvironment but also offers a strategy to design an intelligent conjugated network-based artificial antioxidase with a highly surface-exposed active site.

Structure optimization of heterogeneous compound eye camera for improving the detection performance.

To achieve fast location, precise tracking and accurate identification over a large field of view (FOV), we have proposed a heterogeneous compound eye camera (HeCECam), which consists of a heterogeneous compound eye array, an optical relay system and a CMOS detector. However, the current HeCECam can hardly acquire high-precision 3D information of the targets to realize these applications. To solve this challenge, we propose a scheme on optimizing the structure of the HeCECam to improving the detection performance, including the optimization of the distribution uniformity of the sub-eyes with the proposed "Three-direction center-of-gravity subdivision (TGS)" and the enhancement of the compatibility between heterogeneous compound eyes and the optical relay system with the proposed compensation method for tilt. The TGS significantly reduces the distribution unevenness of sub-eyes down to 117% from the previous 152%, and provides symmetry to the heterogeneous compound eye array. The tilt compensation effectively addresses previous imaging defects, such as distortion of sub-images, increased stray light, and support structures being imaged, and it improves the imaging clarity of the system, especially in external FOV. Based on two proposed methods, we re-design and fabricate the heterogeneous compound eye array to obtain a high-performance prototype. To verify the imaging capacities of the optimized HeCECam, a series of comparison experiments are performed, including blank scene imaging, FOV tests, resolution verification and real-world scene imaging. The results show that the previous imaging defects have been well eliminated, and the optimized prototype has stronger resolving power and wider FOV. This allow the HeCECam to perform better in subsequent practical applications, such as wide-area surveillance, forewarning, and navigation.

Masking effects on iso-valeric acid recognition by sub-threshold odor mixture.

Masking unpleasant odors with pleasant-smelling odorants has a long history and is utilized in various industries, including perfumery and consumer products. However, the effectiveness of odor masking is idiosyncratic and temporary. In this study, we employed Sniff olfactometry (SO) to investigate the psychophysics of masking using brief 70 ms stimulations with mixtures of the mal-odorant iso-valeric acid (IVA) and different masking agents. IVA is a component of human sweat that can overpower its smell and is often associated with unpleasant descriptors such as "gym locker," "smelly feet," "dirty clothes," and so on. Traditionally, high concentrations of pleasant-smelling odorants are used to mitigate the unpleasantness of IVA in situations involving clothing or environments contaminated with IVA. To examine the masking effects of sub-threshold levels of various masking agents (neohivernal, geraniol, florhydral, decanal, iso-longifolanone, methyl iso-eugenol, and s-limonene) on IVA, we conducted experiments using SO to measure the probability of recognizing IVA after 70 ms stimulations with headspaces containing mixtures of super-threshold concentrations of IVA and sub-threshold concentrations of IVA suppressors. The study involved nine subjects, and on average, a single masking agent was found to decrease IVA recognition probability by 14-72%. Moreover, a sub-threshold odor mixture consisting of 6 masking agents demonstrated a substantial decrease in IVA recognition, with a reduction of 96%.

Nucleolar reorganization after cellular stress is orchestrated by SMN shuttling between nuclear compartments.

Spinal muscular atrophy is an autosomal recessive neuromuscular disease caused by mutations in the multifunctional protein Survival of Motor Neuron, or SMN. Within the nucleus, SMN localizes to Cajal bodies, which are associated with nucleoli, nuclear organelles dedicated to the first steps of ribosome biogenesis. The highly organized structure of the nucleolus can be dynamically altered by genotoxic agents. RNAP1, Fibrillarin, and nucleolar DNA are exported to the periphery of the nucleolus after genotoxic stress and, once DNA repair is fully completed, the organization of the nucleolus is restored. We find that SMN is required for the restoration of the nucleolar structure after genotoxic stress. During DNA repair, SMN shuttles from the Cajal bodies to the nucleolus. This shuttling is important for nucleolar homeostasis and relies on the presence of Coilin and the activity of PRMT1.

Degradation of Diclofenac by Loaded Solid Superbase-Activated Persulfate.

Alkali-activated persulfate (PS) is widely used in situ in chemical oxidation processes; however, studies on the innovation of the alkali activation process are very limited. Two supported solid superbases, namely KNO3/γ-Al2O3 (KAl) and KNO3/SBA-15/MgO (KSM), respectively, were prepared and used to activate persulfate to degrade DCF in this work. The results showed that the superbases elevated the solution pH once added and thus could catalyze persulfate to degrade diclofenac efficiently above pH 10.5. The catalytic efficiency of KAl was close to that of sodium hydroxide, and that of KSM was the highest. The mechanism might be that, in addition to raising the solution pH, some potassium existed as K2O2, which had a strong oxidizing effect and was conducive to DCF removal. Hydroxyl, sulfate and superoxide radicals were all found in the reaction system, among which hydroxyl might play the most important role. The material composition ratio, common anion and humic acid all had some influences on the catalytic efficiency. A total of five intermediates were found in the KSM/PS oxidation system, and six oxidation pathways, which were hydroxylation, dehydrogen, dechlorination, dehydration, decarboxylation, and C-N bond breakage, might be involved in the reaction process. Several highly toxic oxidation products that should be paid attention to were also proposed.

Black carbon, soil organic matter molecular signatures under different land uses in Shenyang, China and relationship with PAHs.

The content, composition and molecular signatures of soil organic matter (SOM) have important influences on the cycle of soil organic carbon (SOC) and the partitioning of polycyclic aromatic hydrocarbons (PAHs) in soil. Seventy-nine soil samples from farmland, forest and urban areas were collected in Shenyang, China to investigate black carbon (BC) content, SOM molecular signatures varied with land use patterns, as well as the relationship with PAHs. The content of BC in urban soils was significantly higher than that of farmland and forest. BC was a key contributor of urban SOM which accounted for 0.35 ± 0.31 of SOC in urban soil. Based on BC/SOC ratio, the main sources of BC were identified as fossil fuel combustion for urban soils, while for farmland and forest soils, it is the mixed results of fossil fuel combustion and biomass burning. All categories of PAHs in urban soils showed the highest level compared to farmland and forest soils. Pearson's correlation analysis results showed there were significant positive correlations between BC and PAHs categories in urban soils, indicating the important role of BC in the accumulation of PAHs in soil. SOM from each of the two different land use patterns can be distinguished by molecular signatures. Urban SOM had abundant molecular markers derived from condensed organic carbon inputs, which was consistent with the BC/SOC value. Farmland SOM had abundant carbon from vegetation and microorganisms, and forest SOM was rich in organic carbon from fresh plant materials. The markers enriched in urban SOM showed significant correlations with most PAHs categories, highlighting the affinity of urban SOM for PAHs at the molecular level. This study contributed to understanding the impact of land management methods on SOM molecular composition signatures and its influence on PAHs occurrence in soil, providing a theoretical basis for regional soil pollution management.

Sources of antimony contamination and its migration into water systems of Xikuangshan, China: Evidence from hydrogeochemical and stable isotope (H, O, S, and Sr) signatures.

The Xikuangshan (XKS) mine was selected for a comprehensive Sb-related hydrogeochemical study because of its significant Sb contamination in water systems. Hydrochemical data, specifically multi-isotope (H, O, S, and Sr) data, were conducted to elucidate the primary sources and migration processes of Sb responsible for water system contamination. At the XKS Sb mine, water is near-neutral to alkaline and is characterized by high concentrations of SO42- and Sb. Sb occurs as Sb(OH)6- (the dominant species) in these oxidized waters. The hydrochemistry is mainly controlled by carbonate dissolution and silicate weathering. δ2HH2O and δ18OH2O values indicate that the infiltration recharge of mine water and mining activities regulate the migration of Sb in groundwater. δ34SSO4 and δ18OSO4 values indicate that dissolved SO42- and Sb primarily come from stibnite oxidation, bacterial SO42- reduction has either not occurred or is extremely weak, and the reductive dissolution of Fe (III) hydroxides does not significantly affect Sb migration in water. The 87Sr/86Sr ratios further indicate that the discharge of solid mine wastes leaching and smelting water is a crucial source of Sb contamination in groundwater. In addition, the relationship between δ34SSO4 and δ87Sr values suggests the complexity of the contamination source and migration of Sb in water. Finally, a robust conceptual hydrogeochemical model was developed using isotopic tools in combination with detailed hydrogeological and hydrochemistry characterization to describe the contamination source and migration of Sb in water systems at the XKS Sb mine.

Compared with CT/MRI LI-RADS, whether CEUS LI-RADS is worth popularizing in diagnosis of hepatocellular carcinoma?-a direct head-to-head meta-analysis.

Background: Until now, there has been no systematic review or meta-analysis of direct head-to-head studies that compare two liver imaging reporting and data system (LI-RADS) algorithms, contrast-enhanced ultrasound (CEUS) LI-RADS and contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) LI-RADS, for the diagnostic efficacy of hepatocellular carcinoma. The purpose of this study was to identify and head-to-head compare the diagnostic performance of both LI-RADS algorithms for hepatocellular carcinoma. Methods: We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases from the inception of each database to April 26, 2022, to find the comparative study of both LI-RADS algorithms for hepatocellular carcinoma at risk of patients who underwent both LI-RADS algorithms. Eligibility criteria included only studies published in English, full reports published, both retrospective and prospective studies. Liver histology or imaging follow-up results served as the reference standard. We analyzed the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic curve to determine summary estimates. The Quality Assessment of Diagnostic Accuracy Studies was utilized to assess the methodological quality. Results: In 5 included studies (831 patients, 877 lesions), the pooled sensitivity and pooled specificity of CEUS LR-5 were 0.79, 0.81, and 0.78, 0.79 in CT/MRI LR-5, respectively. The pooled sensitivity and pooled specificity of CEUS LR-4/5 were 0.86, 0.70, and 0.93, 0.59 in CT/MRI LR-4/5, respectively. There was no obvious difference between the two LI-RADS algorithms for hepatocellular carcinoma, and there was no significant statistical difference between two LR-M algorithms for non-hepatocellular carcinoma malignancies. Conclusions: The results of our analysis demonstrated that CEUS LI-RADS has satisfactory diagnostic performance similar to that of CT/MRI LI-RADS, which provides a theoretical basis for the popularization of CEUS LI-RADS for diagnosing HCC. This work was supported by Sichuan Science and Technology Program (No. 2020YFS0211). We registered this study on the international prospective register of systematic reviews (PROSPERO, CRD42022328107) before the search step.

Awaken Immune Cells by Hapten Enhanced Intratumoral Chemotherapy with Penicillin Prolong Pancreatic Cancer Survival.

Intratumoral immunotherapy is well studied and is ongoing, but few studies have evaluated the relationship between of cytotoxic drugs intratumoral injection (CDI) and hapten-enhanced cytotoxic drugs intratumoral injection (HECDI) and patient survival. The objectives of this study include comparisons to explore possible associations between the proportions of treatment-induced cytokines and autologous antibodies to tumor-associated antigens (TAAs) and the relative size of the abscopal effects concurring. CDIs contain oxidant and cytotoxic drugs, HECDIs contains the same drug plus penicillin as the new Hapten. Of the 33 patients with advanced pancreatic cancer, 9 received CDI, 20 received HECDI, and 4 (control group) received placebo. Serum levels of cytokines and autoantibodies of TAAs were detected and compared after therapy. The 1-year survival rate was 11.11% for CDI and 52.63% for HECDI (P= 0.035). In the general analysis of cytokines, HECDI exhibited an increasing level of IFN-γ and IL-4, and the non-hapten CDI showed a rising level of IL-12 (P = 0.125, 0.607, & 0.04). Participants who did not receive chemotherapy had significant differences in the level of Zeta autoantibody only before and after HECDI; However, IMP1 levels in patients with previous chemotherapy experience were significantly different before and after HECDI and CDI treatment (P≤0.05, P = 0.316). After HECDI treatment, TAA autoantibodies of RalA, Zeta, HCC1, p16 increased (P = 0.429, 0.416, 0.042, 0.112). The elevated levels of CXCL8, IFN-γ, HCC1, RalA, Zeta, and p16 observed in HECDI may be attributed to the abscopal effect (P = 0.012 & 0.013). Overall survival rates indicated that HECDI treatment extended participants' lives.

Synergistic Enzyme-Mimetic Catalysis-Based Non-Thermal Sonocavitation and Sonodynamic Therapy for Efficient Hypoxia Relief and Cancer Ablation.

Non-invasive cancer treatment strategies that enable local non-thermal ablation, hypoxia relief, and reactive oxygen species (ROS) production to achieve transiently destroying tumor tissue and long-term killing tumor cells would greatly facilitate their clinical applications. However, continuously generating oxygen cavitation nuclei, reducing the transient cavitation sound intensity threshold, relieving hypoxia, and improving its controllability in the ablation area still remains a significant challenge. Here, in this work, an Mn-coordinated polyphthalocyanine sonocavitation agent (Mn-SCA) with large d-π-conjugated network and atomic Mn-N sites is identified for the non-thermal sonocavitation and sonodynamic therapy in the liver cancer ablation. In the tumor microenvironment, the catalytical generation of oxygen assists cavitation formation and generates microjets to ablate liver cancer tissue and relieve hypoxia, this work reports for the first time to utilize the enzymatic properties of Mn-SCA to lower the cavitation threshold in situ. Moreover, under pHIFU irradiation, high reactive oxygen species (ROS) production can be achieved. The two merits in liver cancer ablation are demonstrated by cell destruction and high tumor inhibition efficiency. This work will help deepen the understanding of cavitation ablation and the sonodynamic mechanisms related to the nanostructures and guide the design of sonocavitation agents with high ROS production for solid tumor ablation.