Therapeutic Suppression of Atherosclerotic Burden and Vulnerability via Dll4 Inhibition in Plaque Macrophages Using Dual-Targeted Liposomes.

Atherosclerosis, characterized by chronic inflammation within the arterial wall, remains a pivotal concern in cardiovascular health. We developed a dual-targeted liposomal system encapsulating Dll4-targeting siRNA, designed to selectively bind to pro-inflammatory M1 macrophages through surface conjugation with anti-F4/80 and anti-CD68 antibodies. The Dll4-targeting siRNA is then delivered to the macrophages, where it silences Dll4 expression, inhibiting Notch signaling and reducing plaque vulnerability. Emphasizing accuracy in targeting, the system demonstrates effective suppression of Dll4, a key modulator of atherosclerotic progression, and vulnerability via VSMCs phenotypic conversion and senescence. By employing liposomes for siRNA delivery, we observed enhanced stability and specificity of the siRNA. Alongside the therapeutic efficacy, our study also evaluated the safety profile and pharmacokinetics of the dual-targeted liposomal system, revealing favorable outcomes with minimal off-target effects and optimal biodistribution. The integration of RNA interference techniques with advanced nanotechnological methodologies signifies the importance of targeted delivery in this therapeutic approach. Preliminary findings suggest a potential attenuation in plaque development and vulnerability, indicating the therapeutic promise of this approach. This research emphasizes the potential of nanocarrier-mediated precision targeting combined with a reassuring safety and pharmacokinetic profile for advancing atherosclerosis therapeutic strategies.

H-Bonds Enhanced Natural Polyphenols Bined Polysaccharide/Gelatin Composites with Controlled Photothermal Stimulation Phase Transition for Wound Care.

Severe open wounds should be closed immediately and regularly undergo re-examination and debridement. Therefore, dressings should effectively cover the wound, creating a moist environment for healing while meeting mechanical requirements for daily movement and adaptability. Herein, a low-cost and easy-to-prepare plant polysaccharide hydrogel was reported. The Mesona chinensis Benth polysaccharide strengthened the hydrogel network by hydrogen bonding and changed the phase transition temperature, but retained the thermal response characteristics of the hydrogel. By adjusting the polysaccharide concentration, MepGel(1) can be prepared to remain stable as a semisolid at body temperature and transform into a shear-thinning semifluid state when appropriately heated. The composite hydrogel could be easily shaped, effectively closing wounds of different shapes, while maintaining excellent mechanical properties. Importantly, this composite hydrogel had a near-infrared photothermal effect resulting in excellent antibacterial effect and collided with its own thermal response producing functions conducive to wound care, like accelerating the self-healing of the dressing, achieving re-adhesion, and further covering the wound. Furthermore, the hydrogel had excellent biocompatibility, enhancing immunity and promoting healing of bacterial-infected wounds. The low cost and rich functionality demonstrated by MepGel had the potential to face the enormous challenges and economic burden of clinical wound healing.

The Use of Water Sac Dilation in Resecting Parapharyngeal Space Benign Tumor via Transoral Approach.

OBJECTIVES: To evaluate the effectiveness of employing the water sac dilation (WSD) method during endoscopy-assisted transoral resection of parapharyngeal space benign tumor (PSBT). METHODS: Between February 2017 and January 2022, a total of 32 patients diagnosed with PSBT were included in this prospective study and were randomly allocated into two groups: the WSD group and the control group. Tumors of the WSD group patients were all dissected using the WSD method. RESULTS: The final numbers of studied patients in WSD group and control group were 17 and 15, respectively. The basic information was comparable between these two groups of patients. All these patients successfully underwent tumor resection via transoral approach. The operation time, intraoperative blood loss, drainage volume on the first postoperative day, drainage duration, and the total drainage volume in the WSD group patients were significantly lower than those in the control group patients (all p < 0.05). No surgical complications occurred, and no residual tumor or recurrence could be identified at 6 months after surgery in both groups of patients. CONCLUSION: The application of the WSD method in endoscopy-assisted transoral resection of PSBT effectively attenuated intraoperative injury, improved surgical efficiency, and accelerated postoperative recovery. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Four novel species of Pleurotheciaceae collected from freshwater habitats in Jiangxi Province, China.

During an investigation of fungal diversity from freshwater environments in different regions in Jiangxi Province, China, four interesting species were collected. Morphology coupled with combined gene analysis of an ITS, LSU, SSU, and rpb2 DNA sequence data showed that they belong to the family Pleurotheciaceae. Four new species, Pleurotheciella ganzhouensis, Pla. irregularis, Pla. verrucosa, and Pleurothecium jiangxiense are herein described. Pleurotheciella ganzhouensis is characterized by its capsule-shaped conidia and short conidiophores, while Pla. irregularis has amorphous conidiophores and 3-septate conidia. Pleurotheciella verrucosa has cylindrical or verrucolose conidiogenous cells, 1-septate, narrowly fusiform, meniscus or subclavate conidia. Pleurothecium jiangxiense characterized in having conidiogenous cells with dense cylindrical denticles and short conidiophores. Pleurothecium obovoideum was transferred to Neomonodictys based on phylogenetic evidence. All species are compared with other similar species and comprehensive descriptions, micrographs, and phylogenetic data are provided.

Assessment of the efficacy and safety of auricular keloids excision followed by 5-aminolevulinic acid photodynamic therapy.

BACKGROUND: Auricular keloids are a significant clinical challenge, which adversely affect the life of the patient at the level of aesthetic and psychological well-being. Despite various treatment modalities, a universally effective therapy has yet to be established. Photodynamic therapy (PDT) offers a promising approach by inhibiting the abnormal proliferation of fibroblasts while minimizing damage to surrounding healthy cells and tissues. This study evaluates the clinical outcomes of auricular keloid patients treated with excision followed by 5-aminolevulinic acid photodynamic therapy (ALA-PDT). METHODS: This study included 8 patients diagnosed with auricular keloids based on pathological examination and clinical presentation. Following surgical excision of the auricular keloids, topical 5-ALA solution was applied for 4 hours. Then each lesion was irradiated with 120 J/cm² using a red LED (635-nm laser) for 20 minutes. Patients received 3-5 courses of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) during and after the surgery. RESULTS: Among the 8 patients treated, auricular keloids were completely controlled with the combination therapy. During a follow-up period of 2.7 years (range: 1.8-4.1 years), all patients exhibited excellent outcomes with no recurrence of keloids. CONCLUSIONS: The combination of surgical excision and 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective and safe treatment for auricular keloids. This combined approach shows promise as an alternative clinical treatment for managing auricular keloids.

Synthesis and Evaluation of 99mTc-Labeled DPro-Gly-Containing Tracers Targeting PSMA.

The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many 99mTc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these 99mTc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using DPro-Gly as the linker was synthesized and three 99mTc-labeled complexes ([99mTc]Tc-EUKPG-EDDA, [99mTc]Tc-EUKPG-TPPTS, [99mTc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [99mTc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both in vivo and in vitro. Therefore, [99mTc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.

Biochar amendment alleviates soil microbial nitrogen and phosphorus limitation and increases soil heterotrophic respiration under long-term nitrogen input in a subtropical forest.

Nitrogen (N) and carbon (C) inputs substantially affect soil microbial functions. However, the influences of long-term N and C additions on soil microbial resource limitation and heterotrophic respiration-fundamental microbial functional traits-remain unclear, impeding the understanding of how soil C dynamics respond to global change. In this study, the responses of soil microbial resource limitation and heterotrophic respiration (Rh) to 7-year N and biochar (BC) additions in a subtropical Moso bamboo (Phyllostachys edulis) plantation were investigated. We used eight treatments: Control, no N and BC addition; N30, 30 kg N (ammonium nitrate)·hm-2·a-1; N60, 60 kg N·hm-2·a-1; N90, 90 kg N·hm-2·a-1; BC20, 20 t BC (originating from Moso bamboo chips) hm-2; N30 + BC20, 30 kg N·hm-2·a-1 + 20 t BC hm-2; N60 + BC20, 60 kg N·hm-2·a-1 + 20 t BC hm-2; and N90 + BC20, 90 kg N·hm-2·a-1 + 20 t BC hm-2. Soil microbes were co-limited by N and phosphorus (P) and not limited by C in the control treatments. Long-term N addition enhanced soil microbial N and P limitation but significantly reduced soil Rh by 15.1 %-20.0 % relative to that in the control treatments. BC amendment alleviated soil microbial N and P limitation and significantly decreased C use efficiency by 10.9 %-42.1 % but increased Rh by 33.6 %-91.6 % in the long-term N-free and N-supplemented treatments (P < 0.05). Soil C- and N-acquisition enzyme activities were the dominant drivers of soil microbial resource limitation. Furthermore, microbial resource limitation was a more reliable predictor of Rh than soil resources or microbial biomass. The results suggested that long-term N and BC additions affect Rh by regulating microbial resource limitation, highlighting its significance in understanding soil C cycling under environmental change.

Novel 99mTc-Labeled Mannose Derivative as a Highly Promising Single Photon Emission Computed Tomography Probe for Tumor Imaging.

18F-2-fluoro-2-deoxy-d-glucose ([18F]FDG) has been the most used positron emission tomography imaging agent for clinical applications. Single photon emission computed tomography (SPECT) imaging is cheaper and used more widely for diagnostic use, but there is no SPECT tumor imaging agent for clinical applications comparable to [18F]FDG. Mannose is a C2 epimer of glucose and can also be transported into tumor cells via glucose transporters (GLUTs). To develop a novel SPECT tumor imaging agent with satisfactory tumor uptake and tumor/nontarget ratios, here a mannose derivative (CN7DM) was synthesized and radiolabeled with technetium-99m to prepare [99mTc]Tc-CN7DM. The six-coordinated structure of [99mTc]Tc-CN7DM was confirmed by the corresponding rhenium compound (Re-CN7DM). [99mTc]Tc-CN7DM was transported into cancer cells via GLUTs and may be trapped in the cancer cells by electrostatic attraction. The probe exhibited high uptake in tumors and low uptake in nontarget tissues in mice bearing different tumors, indicating that [99mTc]Tc-CN7DM exhibited promising potential for SPECT tumor imaging and warranted further clinical investigation.

Multi-Scale Spatial Attention-Based Multi-Channel 2D Convolutional Network for Soil Property Prediction.

Visible near-infrared spectroscopy (VNIR) is extensively researched for obtaining soil property information due to its rapid, cost-effective, and environmentally friendly advantages. Despite its widespread application and significant achievements in soil property analysis, current soil prediction models continue to suffer from low accuracy. To address this issue, we propose a convolutional neural network model that can achieve high-precision soil property prediction by creating 2D multi-channel inputs and applying a multi-scale spatial attention mechanism. Initially, we explored two-dimensional multi-channel inputs for seven soil properties in the public LUCAS spectral dataset using the Gramian Angular Field (GAF) method and various preprocessing techniques. Subsequently, we developed a convolutional neural network model with a multi-scale spatial attention mechanism to improve the network's extraction of relevant spatial contextual information. Our proposed model showed superior performance in a statistical comparison with current state-of-the-art techniques. The RMSE (R²) values for various soil properties were as follows: organic carbon content (OC) of 19.083 (0.955), calcium carbonate content (CaCO3) of 24.901 (0.961), nitrogen content (N) of 0.969 (0.933), cation exchange capacity (CEC) of 6.52 (0.803), pH in H2O of 0.366 (0.927), clay content of 4.845 (0.86), and sand content of 12.069 (0.789). Our proposed model can effectively extract features from visible near-infrared spectroscopy data, contributing to the precise detection of soil properties.

Increased CD56 expression after photodynamic therapy indicates an increased natural killer cell count following early photodynamic therapy for cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. Photodynamic therapy (PDT) is a promising therapeutic method for managing cSCC due to its proven ability to target specific areas over time and its low risk of side effects. PDT may cause tissue damage and vascular shutdown, and may regulate local immunological responses. The present study aimed to investigate and compare the early lymphocyte modifications before and after PDT for SCC. A total of 10 patients with SCC were identified by pathological investigation. Initially, all wounds were treated with 20% aminolevulinic acid (ALA)-PDT as the initial stage in the therapeutic procedure. The wounds were treated by exposing them to red LED light with a wavelength of 635 nm, an energy density of 100 J/cm2 and an intensity of 80 mW/cm2. The tumor tissue was surgically removed 24 h later, and another round of PDT therapy was administered. Immunohistochemistry for CD3 and CD56 was conducted on the wound tissue post-surgery. If the wound showed granulation, necrosis or secretion, debridement was added to the therapy. All patients were monitored for 0.6-1.0 year post-treatment. ALA-PDT combination surgery fully controlled the tumor tissue in all 10 patients. The immunohistochemical analysis of the wound tissues showed that the expression of CD56 increased, while the expression of CD3 was not different after photodynamic therapy. These results also indirectly indicated that the overall count of NK cells in the 10 patients increased, nevertheless, there was no alteration in the T lymphocyte count. In conclusion, the ALA-PDT combination surgical therapy for cSCC demonstrates favorable results. An increase in CD56 expression may be a mechanism for the effective treatment of cSCC with PDT.

Preparation and Evaluation of a Novel 99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent.

Poly ADP-ribose polymerase (PARP) plays an important role in the DNA repair process and has become an attractive target for cancer therapy in recent years. Given that niraparib has good clinical efficacy as a PARP inhibitor, this study aimed to develop radiolabeled niraparib derivatives for tumor imaging to detect PARP expression and improve the accuracy of stratified patient therapy. The niraparib isonitrile derivative (CNPN) was designed, synthesized, and radiolabeled to obtain the [99mTc]Tc-CNPN complex with high radiochemical purity (>95%). It was lipophilic and stable in vitro. In HeLa cell experiments, the uptake of [99mTc]Tc-CNPN was effectively inhibited by the ligand CNPN, indicating the binding affinity for PARP. According to the biodistribution studies of HeLa tumor-bearing mice, [99mTc]Tc-CNPN has moderate tumor uptake and can be effectively inhibited, demonstrating its specificity for targeting PARP. The SPECT imaging results showed that [99mTc]Tc-CNPN had tumor uptake at 2 h postinjection. All of the results of this study indicated that [99mTc]Tc-CNPN is a promising tumor imaging agent that targets PARP.

Progressively worsening ptosis in a woman: A case report.

Key Clinical Message: Filler injections into the upper eyelid may cause levator aponeurosis fibrosis and ptosis. This risk must be considered. When ptosis appears, treatment might be difficult. Understanding the upper eyelid anatomy and procedures is essential to prevent eyelid damage. Abstract: Ptosis is a prevalent condition in cosmetic surgery that occurs due to malfunction of the levator palpebrae superioris or insufficient Müller muscle action. It is characterized by the upper eyelid edge appearing lower than usual when seen at eye level. Ptosis may be categorized into congenital and acquired forms. The primary cause of congenital ptosis is attributed to abnormalities of the levator palpebrae superioris muscle or the motor nerve innervation that controls it. The condition arises from atypical development and malfunction of the oculomotor system. Acquired ptosis may be classified into many categories including traumatic, neurogenic, myogenic, senile, mechanical, and fake ptosis. Currently, there is little documentation of ptosis resulting from the degeneration of the aponeurosis of the muscle in the upper eyelid. We received a case of ptosis caused by fibrosis of the levator palpebrae superioris aponeurotic membrane. We used the technique of levator palpebrae superioris great advancement. The levator palpebrae superioris-Müller muscle was folded to create a stable composite construction via the levator palpebrae superioris high progress.

Effect of postharvest grape dehydration on chemical composition, antioxidant activity and sensory characeteristics of Marselan wines.

To explore the effect of postharvest dehydration on grape berries and wine quality, we determined physicochemical properties, polyphenols, antioxidant activities, volatile compounds and sensory characteristics for wines brewed by 'Marselan' (Vitis vinifera L.) grapes with 0%, 10%, 15%, 20%, and 25% of water loss. The result showed that postharvest dehydration improved the alcohol content, residual sugar and titratable acidity of Marselan wine. Phenolic compounds and antioxidant activities in wines with a dehydration of 20% have significantly increased. Postharvest dehydration increased the contents of isobutanol, isoamyl alcohol, phenylethyl alcohol, ethyl acetate, isoamyl acetate and ethyl butyrate in Marselan wines, and enhanced the floral, fruity and sweet taste of wines. Marselan wine had the lowest acceptability score under the condition of severe dehydration (25% dehydration), which was related to the significant increase of tannins content. In summary, postharvest dehydration was beneficial in improving the quality of Marselan wine.

Case Report: Coil embolization of ascending aortic pseudoaneurysm in patient with Behcet's disease.

Background: Behcet's disease (BD) is a systematic vasculitis that affects vessels with various sizes, presenting as venous thrombosis and arterial pseudoaneurysms. The most severe manifestation in BD is ascending aortic pseudoaneurysm, which is associated with high risks of rupture and mortality. Case presentation: We present a case of ascending aortic pseudoaneurysm in a 50-year-old patient with BD. After preoperative evaluation, coil embolization was successfully performed to treat the pseudoaneurysm, resulting in a satisfactory outcome at the 1-year follow-up. Conclusion: Coil embolization serves as an effective treatment option for ascending aortic pseudoaneurysm in BD when open surgical repair and stent graft placement are unsuitable.

Regulatory networks of senescence-associated gene-transcription factors promote degradation in Moso bamboo shoots.

Bamboo cultivation, particularly Moso bamboo (Phyllostachys edulis), holds significant economic importance in various regions worldwide. Bamboo shoot degradation (BSD) severely affects productivity and economic viability. However, despite its agricultural consequences, the molecular mechanisms underlying BSD remain unclear. Consequently, we explored the dynamic changes of BSD through anatomy, physiology and the transcriptome. Our findings reveal ruptured protoxylem cells, reduced cell wall thickness and the accumulation of sucrose and reactive oxygen species (ROS) during BSD. Transcriptomic analysis underscored the importance of genes related to plant hormone signal transduction, sugar metabolism and ROS homoeostasis in this process. Furthermore, BSD appears to be driven by the coexpression regulatory network of senescence-associated gene transcription factors (SAG-TFs), specifically PeSAG39, PeWRKY22 and PeWRKY75, primarily located in the protoxylem of vascular bundles. Yeast one-hybrid and dual-luciferase assays demonstrated that PeWRKY22 and PeWRKY75 activate PeSAG39 expression by binding to its promoter. This study advanced our understanding of the molecular regulatory mechanisms governing BSD, offering a valuable reference for enhancing Moso bamboo forest productivity.

CircST6GAL1 knockdown alleviates pulmonary arterial hypertension by regulating miR-509-5p/multiple C2 and transmembrane domain containing 2 axis.

BACKGROUND: Hypertension is a main contributing factor of cardiovascular diseases; deregulated circular RNAs are involved in the pathogenesis of pulmonary arterial hypertension (PAH). Herein, we evaluated the function and mechanism of circST6GAL1 in PAH process. METHODS: Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic environment for functional analysis. The cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, and flow cytometry assays were used to investigate cell proliferation, migration, and apoptosis. qRT-PCR and Western blotting analyses were used for level measurement of genes and proteins. The binding between miR-509-5p and circST6GAL1 or multiple C2 and transmembrane domain containing 2 (MCTP2) was analyzed by dual-luciferase reporter, RNA immunoprecipitation, and pull-down assays. The monocrotaline (MCT)-induced PAH mouse models were established for in vivo assay. RESULTS: CircST6GAL1 was highly expressed in PAH patients and hypoxia-induced HPASMCs. Functionally, circST6GAL1 deficiency reversed hypoxia-induced proliferation and migration, as well as apoptosis arrest in HPASMCs. Mechanistically, circST6GAL1 directly targeted miR-509-5p, and MCTP2 was a target of miR-509-5p. Rescue assays showed that the regulatory effects of circST6GAL1 deficiency on hypoxia-induced HPASMCs were abolished. Moreover, forced expression of miR-509-5p suppressed HPASMC proliferation and migration and induced cell apoptosis under hypoxia stimulation, while these effects were abolished by MCTP2 overexpression. Moreover, circST6GAL1 silencing improved MCT-induced pulmonary vascular remodeling and PAH. CONCLUSION: CircST6GAL1 deficiency reversed hypoxia-induced proliferation and migration, as well as apoptosis arrest in HPASMCs, and alleviated pulmonary vascular remodeling in MCT-induced PAH mouse models through the miR-509-5p/MCTP2 axis, indicating a potential therapeutic target for PAH.

Partial Alleviation of Homologous Superinfection Exclusion of SeMNPV Latently Infected Cells by G1 Phase Infection and G2/M Phase Arrest.

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain a latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV)-latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells and SeMNPV or Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells, and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in the G2/M phase or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that, compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, budded virus (BV) production and occlusion body (OB)-containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post-infection (p < 0.05). Finally, the arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB-containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression and regulation.

Preparation, Biological Evaluation, and First-in-Human Single-Photon Emission Computed Tomography (SPECT) Study of 99mTc-Labeled Prostate-Specific Membrane Antigen (PSMA)-Targeted Radiotracers Containing Triazole with Reduced Kidneys Accumulation.

Prostate-specific membrane antigen (PSMA), a well-established biological marker for prostate cancer (PCa) imaging and therapy, is overexpressed on the surface of prostate cancer lesions. In this study, a triazole ring was introduced into the linker by click chemistry to generate a HYNIC-derived ligand (T), which exhibited good PSMA affinity (Ki = 2.23 nM). Eight stable 99mTc-labeled complexes, [99mTc]Tc-T-Mn (n = 1-8), with hydrophilic properties were synthesized by incorporating different coligands at high radiochemical yields and purities without purification. The radioligands were concentrated in the kidneys of healthy Kunming male mice and were significantly blocked by the PSMA inhibitor ZJ-43. The uptake of the optimized complex [99mTc]Tc-T-M2 was correlated with PSMA, and it had good PSMA affinity (Kd = 5.42 nM). [99mTc]Tc-T-M2 accumulated on LNCaP (PSMA++) tumors and was significantly blocked by ZJ-43 at 2 h p.i., indicating high PSMA specificity. Relatively suitable kidney uptake was beneficial for reducing kidneys exposure in patients. SPECT/CT imaging of [99mTc]Tc-T-M2 in LNCaP (PSMA++) or 22Rv1 (PSMA+) tumor-bearing mice revealed high tumor uptake, low background uptake (especially low kidney uptake (49.06 ± 9.20 %ID/g) at 2 h p.i.), and obvious inhibition by ZJ-43, whereas PC-3 (PSMA-) tumors were undetectable. A freeze-dried [99mTc]Tc-T-M2 kit was successfully developed (T-M2 kit). Preliminary clinical trials showed that [99mTc]Tc-T-M2 clearly identified small prostate cancer lesions and has potential for clinical application.

Elevated Saliva Pepsin Concentration as a Risk Factor for Asthma in Children with Allergic Rhinitis: A Preliminary Study.

Objective: This study aimed to explore whether saliva pepsin concentration (SPC) could be regarded as a risk factor for the occurrence and unfavorable control of asthma in children with allergic rhinitis. Methods: A prospective study was conducted on a group of 20 consecutive children newly diagnosed with allergic rhinitis and asthma (referred to as the asthma group). All these children underwent fractional exhaled nitric oxide (FeNO) measurement, lung function tests, and assessment of asthma control using the 7-item Childhood Asthma Control Test (C-ACT) score. Simultaneously, a control group consisting of 20 children with simple allergic rhinitis, matched for baseline characteristics, was included. SPC measurement was performed in the two groups. Results: The SPC value was significantly higher in the asthma group than that in the control group (165.0 ± 82.8 ng/mL vs 68.4 ± 34.5 ng/mL) (P < 0.001). In the asthma group, SPC was independently associated with FeNO, the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), and forced expiratory flow at 50% and 75% of FVC (FEF50 and FEF75) (all P < 0.05). The severity of nasal symptoms evaluated by the visual analogue scale (N-VAS) was independently associated with FEF75, the maximal mid-expiratory flow (MMEF), and C-ACT score (P < 0.05). Conclusion: Direct pepsin exposure and uncontrolled nasal symptoms may play crucial roles in the pathogenesis and progression of childhood allergic asthma. The SPC value can be considered as a risk factor for asthma in children with allergic rhinitis.