Seed priming with graphene oxide improves salinity tolerance and increases productivity of peanut through modulating multiple physiological processes.

Graphene oxide (GO), beyond its specialized industrial applications, is rapidly gaining prominence as a nanomaterial for modern agriculture. However, its specific effects on seed priming for salinity tolerance and yield formation in crops remain elusive. Under both pot-grown and field-grown conditions, this study combined physiological indices with transcriptomics and metabolomics to investigate how GO affects seed germination, seedling salinity tolerance, and peanut pod yield. Peanut seeds were firstly treated with 400 mg L⁻¹ GO (termed GO priming). At seed germination stage, GO-primed seeds exhibited higher germination rate and percentage of seeds with radicals breaking through the testa. Meanwhile, omics analyses revealed significant enrichment in pathways associated with carbon and nitrogen metabolisms in GO-primed seeds. At seedling stage, GO priming contributed to strengthening plant growth, enhancing photosynthesis, maintaining the integrity of plasma membrane, and promoting the nutrient accumulation in peanut seedlings under 200 mM NaCl stress. Moreover, GO priming increased the activities of antioxidant enzymes, along with reduced the accumulation of reactive oxygen species (ROS) in response to salinity stress. Furthermore, the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) of peanut seedlings under GO priming were mainly related to photosynthesis, phytohormones, antioxidant system, and carbon and nitrogen metabolisms in response to soil salinity. At maturity, GO priming showed an average increase in peanut pod yield by 12.91% compared with non-primed control. Collectively, our findings demonstrated that GO plays distinguish roles in enhancing seed germination, mitigating salinity stress, and boosting pod yield in peanut plants via modulating multiple physiological processes.

CRISPR/Gal4BD-Cas donor adapting systems based on miniaturized Cas proteins for improved gene editing.

Targeted precise point editing and knock-in can be achieved by homology-directed repair(HDR) based gene editing strategies in mammalian cells. However, the inefficiency of HDR strategies seriously restricts their application in precision medicine and molecular design breeding. In view of the problem that exogenous donor DNA cannot be efficiently recruited autonomously at double-stranded breaks(DSBs) when using HDR strategies for gene editing, the concept of donor adapting system(DAS) was proposed and the CRISPR/Cas9-Gal4BD DAS was developed previously. Due to the large size of SpCas9 protein, its fusion with the Gal4BD adaptor is inconvenient for protein expression, virus vector packaging and in vivo delivery. In this study, two novel CRISPR/Gal4BD-SlugCas9 and CRISPR/Gal4BD-AsCas12a DASs were further developed, using two miniaturized Cas proteins, namely SlugCas9-HF derived from Staphylococcus lugdunensis and AsCas12a derived from Acidaminococcus sp. Firstly, the SSA reporter assay was used to assess the targeting activity of different Cas-Gal4BD fusions, and the results showed that the fusion of Gal4BD with SlugCas9 and AsCas12a N-terminals had minimal distraction on their activities. Secondly, the HDR efficiency reporter assay was conducted for the functional verification of the two DASs and the corresponding donor patterns were optimized simultaneously. The results demonstrated that the fusion of the Gal4BD adaptor binding sequence at the 5'-end of intent dsDNA template (BS-dsDNA) was better for the CRISPR/Gal4BD-AsCas12a DAS, while for the CRISPR/Gal4BD-SlugCas9 DAS, the dsDNA-BS donor pattern was recommended. Finally, CRISPR/Gal4BD-SlugCas9 DAS was used to achieve gene editing efficiency of 24%, 37% and 31% respectively for EMX1, NUDT5 and AAVS1 gene loci in HEK293T cells, which was significantly increased compared with the controls. In conclusion, this study provides a reference for the subsequent optimization of the donor adapting systems, and expands the gene editing technical toolbox for the researches on animal molecular design breeding.

Neutrophil PPIF exacerbates lung ischemia-reperfusion injury after lung transplantation by promoting calcium overload-induced neutrophil extracellular traps formation.

Lung ischemia-reperfusion (I/R) injury is the main risk factor for primary graft dysfunction and patient death after lung transplantation (LTx). It is widely accepted that the main pathological mechanism of lung I/R injury are calcium overload, oxygen free radical explosion and neutrophil-mediated damage, which leading to the lack of effective treatment options. The aim of this study was to further explore the mechanisms of lung I/R injury after LTx and to provide potential therapeutic strategies. Our bioinformatics analysis revealed that the neutrophil extracellular traps (NETs) formation was closely involved in lung I/R injury after LTx, which was accompanied by up-regulation of peptidylprolyl isomerase F (PPIF) and peptidyl arginine deiminase 4 (PADI4). We further established an orthotopic LTx mouse model to simulate lung I/R injury in vivo, and found that PPIF and PADI4 inhibitors effectively reduced neutrophil infiltration, NETs formation, inflammatory response, and lung I/R injury. In the neutrophil model induced by HL-60 cell line in vitro, we found that PPIF inhibitor cyclosporin A (Cys A) better alleviated calcium overload induced inflammatory response, reactive oxygen species content and NETs formation. Further study demonstrated that interfering with neutrophil PPIF protected mitochondrial function by alleviating store-operated calcium entry (SOCE) during calcium overload and played the above positive role. On this basis, we found that the reduction of calcium content in neutrophils was accompanied by the inhibition of calcineurin (CN) and nuclear factor of activated T cells (NFAT). In conclusion, our findings suggested that neutrophil PPIF could serve as a novel biomarker and potential therapeutic target of lung I/R injury after LTx, which provided new clues for its treatment by inhibiting calcium overload-induced NETs formation.

RpoS sigma factor mediates adaptation and virulence in Vibrio mimicus.

The alternative sigma factor RpoS functions as a regulator of stress and virulence response in numerous bacterial species. Vibrio mimicus is a critical opportunistic pathogen causing huge losses to aquaculture. However, the exact role of RpoS in V. mimicus remains unclear. In this study, rpoS deletion mutant of V. mimicus was constructed through allelic exchange and the phenotypic and transcriptional changes were investigated to determine the function of RpoS. The abilities of growth, motility, biofilm production, hemolytic activity and pathogenicity were significantly impaired in ΔrpoS strain. Stationary-phase cells of ΔrpoS strain showed lower tolerance to H2O2, heat, ethanol, and starvation stress than the wild-type strain. Transcriptome analyses revealed the involvement of rpoS in various cellular processes, notably bacterial-type flagellum synthesis and assembly, membrane synthesis and assembly and response to various stimuli. Phenotypic and RNA-seq analysis revealed that RpoS is required for biofilm formation, stress resistance, and pathogenicity in V. mimicus. Furthermore, ß-galactosidase activity showed that rpoS is essential for optimal transcription of the flgK, fliA, cheA, mcpH mRNA. These results offer significant insight into the function and regulatory network of rpoS/RpoS, thereby improving our understanding and facilitating selection of molecular targets for future prevention strategies against V. mimicus.

Blockade of CCR5+ T Cell Accumulation in the Tumor Microenvironment Optimizes Anti-TGF-ß/PD-L1 Bispecific Antibody.

In the previous studies, anti-TGF-ß/PD-L1 bispecific antibody YM101 is demonstrated, with superior efficacy to anti-PD-L1 monotherapy in multiple tumor models. However, YM101 therapy can not achieve complete regression in most tumor-bearing mice, suggesting the presence of other immunosuppressive elements in the tumor microenvironment (TME) beyond TGF-ß and PD-L1. Thoroughly exploring the TME is imperative to pave the way for the successful translation of anti-TGF-ß/PD-L1 BsAb into clinical practice. In this work, scRNA-seq is employed to comprehensively profile the TME changes induced by YM101. The scRNA-seq analysis reveals an increase in immune cell populations associated with antitumor immunity and enhances cell-killing pathways. However, the analysis also uncovers the presence of immunosuppressive CCR5+ T cells in the TME after YM101 treatment. To overcome this hurdle, YM101 is combined with Maraviroc, a widely used CCR5 antagonist for treating HIV infection, suppressing CCR5+ T cell accumulation, and optimizing the immune response. Mechanistically, YM101-induced neutrophil activation recruits immunosuppressive CCR5+ T cells via CCR5 ligand secretion, creating a feedback loop that diminishes the antitumor response. Maraviroc then cleared these infiltrating cells and offset YM101-mediated immunosuppressive effects, further unleashing the antitumor immunity. These findings suggest selectively targeting CCR5 signaling with Maraviroc represents a promising and strategic approach to enhance YM101 efficacy.

Quantitative Study on the Anticollapse Ability of Casing in Shale Gas Wells under Complex Load Conditions.

Implementing novel technologies, including the "well factory" model and zipper fracturing techniques, has become prevalent in shale gas development. During completion operations such as lowering casing and multistage fracturing, the casing is subjected to many complex loads, reducing its strength and increasing the risk of casing deformation. By establishing a casing wear model and conducting multistage cyclic loading experiments and numerical simulations, we analyzed the change rule of casing anticollapse strength under complex loads, developed a calculation method for casing comprehensive anticollapse ability under complex loads, and applied the method to an illustrative calculation. The study shows that the wear effect during completion has a negligible impact on the strength of the casing. The casing anticollapse strength exhibits a linear decline in correlation with the number of cycles. The zipper fracturing operation resulted in a nonuniform distribution of geo-stress around the well, and the casing anticollapse strength demonstrated a nearly linear decline in correlation with the nonuniformity of geo-stress. In the presence of both internal and external effects, the casing anticollapse strength exhibited a decline exceeding 15%, thereby increasing the risk of casing deformation. This research method can provide computational guidance for preventing casing deformation in field fracturing construction.

Preclinical Evaluation of Dihydropyrazole-Cored Positron Emission Tomography (PET) Ligands for Imaging of Receptor-Interacting Serine/Threonine Protein Kinase 1 (RIPK1) in the Brain.

Receptor-interacting serine/threonine protein kinase 1 (RIPK1) has emerged as an important regulator of pathologic cell death and inflammation and is implicated in the pathologies of various central nervous system diseases. In this study, we reported the development of three potent dihydropyrazole-cored RIPK1 positron emission tomography (PET) ligands [18F]WL1-3. Among these, [18F]WL1 showed specific binding to RIPK1 in mouse brain sections in vitro through autoradiography and exhibited favorable brain kinetics in mice, characterized by a high initial uptake (brain2 min = 4.89% ID/g) and rapid washout (brain60 min = 0.21% ID/g). PET studies in rat brains revealed that [18F]WL1 could readily penetrate the brain with specific binding confirmed by inhibition effects of unlabeled WL1 and GSK'547. Notably, [18F]WL1 showed significant potential in imaging the alterations of RIPK1 in a rat brain of tumor necrosis factor α-induced systemic inflammatory response syndrome model. These findings may pave the way for the future design of potent RIPK1 PET ligands.

Structure-based discovery of a 4,5-Dihydropyrazole-cored PET ligand for imaging of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in the brain.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) regulates programmed cell death and inflammation, contributing to a wide range of human pathologies, including inflammatory disorders, neurodegenerative conditions, and cancer. Despite this, no RIPK1 positron emission tomography (PET) ligand with significant in vivo specificity has been reported to date. In this work, we designed and synthesized a new family of dihydropyrazole-cored ligands suitable for 18F-labeling at the late stage. Among these, WL8 showed a strong binding affinity to RIPK1 (EC50 = 19.9 nM, Kd = 25 nM) and was successfully labeled with 18F in the 6-position of pyridine ring, yielding a high radiochemistry yield of 27.9 % (decay-corrected) and a high molar activity of 18.8-31.2 GBq/µmol. In in vitro autoradiography, [18F]WL8 showed some specific binding in the brain sections of rats and lipopolysaccharide (LPS) model mice. Preliminary PET studies in rat brains revealed that [18F]WL8 could efficiently penetrate the blood-brain barrier and was rapidly washed out. As anticipated, [18F]WL8 exhibited a high initial uptake (brain2min = 4.80 % ID/g) in mouse brains, followed by a rapid washout (brain60min = 0.14 % ID/g), although no clear specific binding to RIPK1 was observed. Moderate in vivo stability was noted for [18F]WL8 in mouse brains with 35.2 % of the parent fraction remaining after 30 min post-administration. Altogether, our work broadens the landscape and offers a new chemotype for RIPK1 PET ligand development.

A GhLac1-centered transcriptional regulatory cascade mediates cotton resistance to Verticillium dahliae through the lignin biosynthesis pathway.

The lignin biosynthesis pathway plays a crucial role in the defense response against V. dahliae in cotton, and it is essential to identify the key regulators in this pathway for disease-resistant breeding. In a previous study, the cotton laccase gene GhLac1 was identified as mediating plant broad-spectrum biotic stress tolerance by manipulating phenylpropanoid metabolism. However, the upstream master regulators and regulatory mechanism of lignin are still largely unknown. This study aims to identify the upstream regulators of GhLac1 and explore the molecular mechanism underlying cotton's disease resistance response to V. dahliae. Through the study, three WRKY, three MYB, and one APETALA2/ETHYLENE RESPONSIVE FACTOR (ERF) TFs were identified as differentially responding to V. dahliae infection in cotton. Among these TFs, GhWRKY30, GhWRKY41, GhMYB42, and GhTINY2 were found to directly bind to the GhLac1 promoter and activate its expression. Transient overexpression of these four TFs in cotton led to increased expression of GhLac1 and other the laccase family members, while knockdown of these TFs resulted in reduced lignin accumulation and increased susceptibility to V. dahliae. Additionally, GhWRKY30 and GhWRKY41 were observed to interact with themselves and with each other, synergistically transactivating the GhLac1 promoter. This study reveals a GhLac1-centered transcriptional regulatory cascade of lignin synthesis that contributes to cotton's defense response by modulating lignin metabolism.

Polydopamine-Based Targeted Nanosystem for Chemo/Photothermal Therapy of Retinoblastoma in a Mouse Orthotopic Model.

Background: At present, the few photothermal/chemotherapy studies about retinoblastoma that have been reported are mainly restricted to ectopic models involving subcutaneous implantation. However, eyeball is unique physiological structure, the blood-retina barrier (BRB) hinders the absorption of drug molecules through the systemic route. Moreover, the abundant blood circulation in the fundus accelerates drug metabolism. To uphold the required drug concentration, patients must undergo frequent chemotherapy sessions. Purpose: To address these challenges above, we need to develop a secure and effective drug delivery system (FA-PEG-PDA-DOX) for the fundus. Methods: We offered superior therapeutic efficacy with minimal or no side effects and successfully established orthotopic mouse models. We evaluated cellular uptake performance and targeting efficiency of FA-PEG-PDA-DOX nanosystem and assessed its synergistic antitumor effects in vitro and vivo. Biodistribution assessments were performed to determine the retention time and targeting efficiency of the NPs in vivo. Additionally, safety assessments were conducted. Results: Cell endocytosis rates of the FA-PEG-PDA-DOX+Laser group became 5.23 times that of the DOX group and 2.28 times that of FA-PEG-PDA-DOX group without irradiation. The fluorescence signal of FA-PEG-PDA-DOX persisted for more than 120 hours at the tumor site. The number of tumor cells (17.2%) in the proliferative cycle decreased by 61.6% in the photothermal-chemotherapy group, in contrast to that of the saline control group (78.8%). FA-PEG-PDA-DOX nanoparticles(NPs) exhibited favorable biosafety and high biocompatibility. Conclusion: The dual functional targeted nanosystem, with the effects of DOX and mild-temperature elevation by irradiation, resulted in precise chemo/photothermal therapy in nude mice model.

The prion-like protein Doppel: A soluble biomarker steering ovarian cancer's peritoneal to circulatory dissemination.

Detecting ovarian cancer (OC) early using existing biomarkers, e.g., cancer antigen 125 (CA125), is challenging due to its ubiquitous expression in many tissues. Doppel, a prion-like protein, expresses in male reproductive organ but absent in female reproductive systems and healthy tissues, but plays an important role in neoangiogenesis. Here, we have shown two platforms, soluble Doppel in sera/ascites and Doppel expressed circulating tumor cells ( Dpl+ CTC) in the whole blood, to detect subsets of epithelial OC (EOC). Increased level of Doppel in the sera of OC patients, in three different cohorts, confirm Doppel as OC specific biomarker. Serum Doppel level distinguishes EOC subtypes and early stages HGSOCs from non-cancerous conditions with high sensitivity and specificity. Stratifying the EOCs based on Doppel level, we categorized them into Doppel-high (Dpl hi ) and Doppel-low (Dpl low ) groups. Using ascites-derived organoids and single cell sequencing of whole ascites of Dpl hi and Dpl low patients, we identify that Doppel induces epithelial-mesenchymal transition (EMT) and creates an immunosuppressive microenvironment, respectively. Doppel levels in the sera/ascites correlate with the changes of Dpl+ CTC number in whole blood, highlighting the association of Doppel-induced EMT with CTC dissemination in circulation. Thus, Doppel-based detection of EOC subtypes could be a promising platform as clinical biomarker and link Doppel-axis with OC dissemination.

Bacterial and Archaeal Communities in Erhai Lake Sediments: Abundance and Metabolic Insight into a Plateau Lake at the Edge of Eutrophication.

The littoral zones of lakes are potential hotspots for local algal blooms and biogeochemical cycles; however, the microbial communities within the littoral sediments of eutrophic plateau lakes remain poorly understood. Here, we investigated the taxonomic composition, co-occurrence networks, and potential functional roles of both abundant and rare taxa within bacterial and archaeal communities, as well as physicochemical parameters, in littoral sediments from Erhai Lake, a mesotrophic lake transitioning towards eutrophy located in the Yunnan-Guizhou Plateau. 16S rRNA gene sequencing revealed that bacterial communities were dominated by Proteobacteria, Bacteroidetes, and Chloroflexi, while Euryarchaeota was the main archaeal phylum. Co-occurrence network analysis revealed that keystone taxa mainly belonged to rare species in the bacterial domain, but in the archaeal domain, over half of keystone taxa were abundant species, demonstrating their fundamental roles in network persistence. The rare bacterial taxa contributed substantially to the overall abundance (81.52%), whereas a smaller subset of abundant archaeal taxa accounted for up to 82.70% of the overall abundance. Functional predictions highlighted a divergence in metabolic potentials, with abundant bacterial sub-communities enriched in pathways for nitrogen cycling, sulfur cycling, and chlorate reduction, while rare bacterial sub-communities were linked to carbon cycling processes such as methanotrophy. Abundant archaeal sub-communities exhibited a high potential for methanogenesis, chemoheterotrophy, and dark hydrogen oxidation. Spearman correlation analysis showed that genera such as Candidatus competibacter, Geobacter, Syntrophobacter, Methanocella, and Methanosarcina may serve as potential indicators of eutrophication. Overall, this study provides insight into the distinct roles that rare and abundant taxa play in the littoral sediments of mesotrophic plateau lakes.

Comprehensive Analysis of Laser Peening Forming Effects on 5083 Aluminum Alloy.

In order to investigate the laws of the laser peening forming process and the effects of laser peening on the surface quality and tensile properties of 5083 aluminum alloy, experiments were conducted utilizing various laser peening paths, energies, and plate thicknesses. Subsequently, laser peening forming experiments were performed on S-shaped and different shapes of aluminum alloy substrates. The impact of different laser peening durations on surface morphology and tensile properties was then analyzed. Results indicated that the largest bending deformation perpendicular to the laser peening path reached 12.5 mm. In cases where the laser peening path was inclined relative to the horizontal direction, torsional deformations were observed in the aluminum alloy plate. For laser energy levels of 5 J, 6 J, and 7 J, deformation amounts were 3.8 mm, 4.9 mm, and 5.4 mm, respectively. Plates with thicknesses of 4 mm exhibited convex deformation, while those with 2 mm thickness showed concave deformation. Furthermore, following one and two laser peening cycles, the residual stresses in the alloy plates were -80 MPa and -107 MPa, the surface hardness increased by 16 HV and 31 HV, the roughness increased by 2.495 µm and 3.615 µm, and the tensile strength increased by 9.5 MPa and 18.5 MPa, respectively.

1,25-D3 ameliorates ischemic brain injury by alleviating endoplasmic reticulum stress and ferroptosis: Involvement of vitamin D receptor and p53 signaling.

Endoplasmic reticulum stress (ERS) and ferroptosis are linked to cerebral ischemia reperfusion injury (CIRI). The neuroprotective properties of 1α, 25-dihydroxyvitamin D3 (VitD3 or 1,25-D3) have been well established; however, the mechanism by which VitD3 treats CIRI through ERS and ferroptosis has not been examined. Hence, we developed middle cerebral artery occlusion/reperfusion (MCAO/R) model in SD rats to ascertain if VitD3 preconditioning mediates ERS and ferroptosis involving of p53 signaling. In this study, we observed that VitD3 can reduce infarction volume and cerebral edema, which leads to the improvement of nerve function. HE, Nissl and Tunel staining showed that VitD3 treatment significantly improved the morphology of neuronal cells and reduced their death. The expression and activation of Vitamin D receptor (VDR), PKR-like ER kinase (PERK), C/EBP-homologous protein (CHOP), p53, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and reactive oxygen species (ROS) in the ischemic penumbral area were detected by real-time qPCR, Western-blotting and Elisa. The results showed that after VitD3 treatment, VDR increased, ERS-related indices (PERK, CHOP) significantly decreased and ferroptosis-related indices (Nrf2, GPX4) increased. As a VDRs antagonist, pyridoxal-5-phosphate (P5P) can partially block the neuroprotective effects of VitD3. Therefore, CIRI can induce ERS and ferroptosis in the ischemic penumbra area and VitD3 may ameliorate nerve damage in CIRI rats by up-regulating VDR, alleviating p53-associated ERS and ferroptosis.

Prognostic value of Naples Prognostic Score in locally advanced cervical cancer patients undergoing concurrent chemoradiotherapy.

This study aimed to investigate the prognostic value of the Naples Prognostic Score (NPS) in patients with locally advanced cervical cancer (LACC) who received curative concurrent chemoradiotherapy (CCRT). Clinicopathological data from 213 (training set) and 106 (validation set) LACC cases undergoing CCRT were retrospectively analyzed. The receiver operating characteristic curve (ROC) was used to compare the predictive ability of NPS and other indicators for survival. Cox proportional hazard regression was conducted for overall survival (OS) and progression-free survival (PFS). A prediction model using a nomogram was developed with independent prognostic factors in the training set and validated in the validation set. The 5-year OS for the NPS = 1, 2, and 3 groups was 56.8%, 45.4%, and 28.9% (P < 0.001), and the 5-year PFS for the NPS = 1, 2, and 3 groups was 44.9%, 36.7%, and 28.4% (P = 0.001), respectively. NPS showed better predictive ability for OS and PFS compared to other indicators. Multivariate regression analysis identified NPS as an independent prognostic factor for OS (P < 0.001) and PFS (P < 0.001). A predictive nomogram based on NPS was established and validated. The C-indices of the nomogram in the training set were 0.722 for OS and 0.683 for PFS, while in the validation set the C-indices were 0.731 for OS and 0.693 for PFS. This study confirmed that preoperative NPS could serve as a useful independent prognostic factor in LACC patients treated with CCRT.

High cure rate and satisfaction in patients with periductal mastitis via the latissimus dorsi myocutaneous flap technique: a retrospective study.

Background: Periductal mastitis (PDM) is a complex benign breast disease with a prolonged course and a high probability of recurrence after treatment. There is a variety of available treatments for PDM, but none of these options have been widely accepted. A standard strategy has been especially difficult to establish in patients with PDM accompanied by large tumors or large skin ruptures, as these seriously affect the appearance of the breasts after surgeries, which can lead to feelings of lower self-esteem among patients. Therefore, finding a reliable volume replacement has become a focus of our research efforts. With the widespread use of latissimus dorsi in breast reconstruction, we attempted to use the latissimus muscle (skin) flap for stage I repair in patients with large-defect PDM. Our study is the first of its kind to evaluate the clinical effect and patient satisfaction of the latissimus dorsi myocutaneous flap (LDMF) technique in PDM. Methods: Thirty-two patients with PDM and more than about 20% loss of breast volume admitted to the Department of Breast Surgery of Shanxi Bethune Hospital from March 2017 to July 2021 were enrolled. After lesion removal, the LDMF technique was applied to these patients for immediate completion of breast contour revision. All patients were periodically followed up to assess the efficacy of the procedure and their satisfaction with the breasts' shape. Results: Three patients (9.4%) developed dorsal effusion after removal of the back drain; six patients (18.8%) developed mild limitation of the activity of the affected upper limb; and three patients (9.4%) experienced local recurrence of inflammation after the operation, all of whom underwent a second operation. The cure rate of the patients treated with LDMF was 90.6%, the overall satisfaction rate of the patients was 96.9%, and doctor's evaluation of satisfaction was 90.6%. Conclusions: In patients with poor results after anti-infective and local treatment and those with more than 20% defect volume following lesion removal, the LDMF technique yields a high cure rate and good patient satisfaction.

The first-in-human preclinical evaluation of the new probe [123I]I-PSMA-7 for real-time intraoperative targeted biopsy and SPECT/CT imaging in prostate cancer.

PURPOSE: PSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [123I]I-PSMA-7. First, we hope that [123I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa. METHODS: We synthesized a high-affinity probe, [123I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [123I]I-PSMA-7 for detecting PCa. RESULTS: Animal experiments verified the safety, targeting and effectiveness of [123I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [123I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging. CONCLUSION: With the aid of [123I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [123I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results. TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023.

Study on the Influence of Temperature and Water Content on the Static Mechanical Properties of Sandstone.

The area of permafrost worldwide accounts for approximately 20% to 25% of land area. In cold-climate regions of China, which are garnering international attention, the study of low-temperature and moisture effects on rock mass mechanical properties is of significant importance. China has a wide area of cold regions. This research can provide a foundation for China's exploration activities in such extreme environments. This paper examines the mechanical behavior of rock specimens subjected to various low temperatures and water contents through uniaxial compression tests. The analysis encompasses failure modes, stress-strain relationships, uniaxial compressive strength (UCS), and elastic modulus (EM) of these specimens. Findings reveal that at lower temperatures, the rock specimens' fracture patterns transition from compressive shear failure to cleavage failure, reflecting a shift from a plastic-elastic-plastic to a plastic-elastic response. Specifically, saturated rocks exhibit a 40.8% decrease in UCS and an 11.4% reduction in EM compared to their dry counterparts. Additionally, in cold conditions, an increased water content in rocks primarily leads to vertical cracking. Under such conditions, saturated rocks show a 52.3% decline in UCS and a 15.2% reduction in EM, relative to their dry state.

Disrupted Microbiota of Colon Results in Worse Immunity and Metabolism in Low-Birth-Weight Jinhua Newborn Piglets.

The Jinhua pig is well known in China due to its delicious meat. However, because of large litter size, low birth weight always happens. This experiment used this breed as a model to research bacterial evidence leading to growth restriction and provide a possible solution linked to probiotics. In this experiment, the differences in organs indexes, colonic morphology, short chain fatty acid (SCFA) concentrations, microbiome, and transcriptome were detected between piglets in the standard-birth-weight group (SG) and low-birth-weight group (LG) to find potential evidence leading to low birth weight. We found that LG piglets had a lower liver index (p < 0.05), deeper colonic crypt depth (p < 0.05), fewer goblet cells (p < 0.05), and more inflammatory factor infiltration. In addition, differentially expressed genes (DEGs) were mainly enriched in B-cell immunity and glucose metabolism, and LG piglets had lower concentrations of SCFAs, especially butyrate and isobutyrate (p < 0.05). Finally, most of the significantly differentially abundant microbes were fewer in LG piglets, which affected DEG expressions and SCFA concentrations further resulting in worse energy metabolism and immunity. In conclusion, colonic disrupted microbiota may cause worse glucose metabolism, immunity, and SCFA production in LG piglets, and beneficial microbes colonized in SG piglets may benefit these harmful changes.

Comparison of 18F-FDG PET/CT and 18F-DOTATATE PET/CT in the diagnosis of multiple metastases in rectal neuroendocrine neoplasms.

This case report describes a 62-year-old male with a notable medical history, including surgically treated bladder cancer and the suspicion of metastatic disease. He underwent 18F-FDG PET/CT imaging as part of the initial diagnostic workup, which identified several marginally hypodense hepatic lesions. These lesions exhibited metabolic activity that was slightly lower than the surrounding hepatic parenchyma, raising concerns for metastatic involvement. Subsequent 18F-DOTATATE PET/CT imaging significantly expanded the diagnostic perspective by identifying multiple somatostatin receptor (SSTR)-positive lesions, not only in the liver but also in lymph nodes and bones. This marked an important diagnostic advancement over the initial FDG PET/CT findings, showcasing the superior sensitivity of 18F-DOTATATE PET/CT in detecting SSTR-expressing tumors. Pathological evaluation after these imaging studies confirmed the diagnosis of a rectal neuroendocrine tumor (NET) with extensive hepatic metastasis, altering the clinical management and therapeutic approach for the patient. This case underscores the pivotal role of integrating 18F-DOTATATE and FDG PET/CT in the diagnostic and therapeutic management of neuroendocrine tumors, highlighting the complementary nature of these imaging modalities. The findings advocate for the use of 18F-DOTATATE PET/CT in cases where NETs are suspected, particularly for its enhanced sensitivity in detecting SSTR-positive lesions across various sites, thereby facilitating a more comprehensive disease assessment and informed therapeutic planning.