Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.

Associations between sociodemographic characteristics and neonatal length of the stay.

BACKGROUND: Infants with past NICU admission have a significantly higher risk of developing neurodevelopmental disorders. Studies have demonstrated an iatrogenic effect of the NICU environment on neurodevelopmental outcomes, even while accounting for physical factors. It is, therefore, critical that an infant's LOS is driven by physical needs versus sociodemographic barriers. METHODS: We leveraged electronic health records and a backward selection regression model to explore physical and sociodemographic predictors of infant LOS. RESULTS: Our results demonstrated that physical predictors (birthweight and ventilator use) accounted for the majority of variance in our model but that a sociodemographic predictor, mean visits per day, was also significant. CONCLUSIONS: Infants who were visited more frequently experienced a shorter LOS, possibly due to increased parental involvement resulting in more individualized care and directly impacting infant stability and morbidity. By supporting visitation, we can reduce the costs of lengthy NICU hospitalizations while improving infant and parent health and well-being.

Radiotherapy enhances efficacy of PD-1 inhibitors in advanced hepatocellular carcinoma: A propensity-matched real-world study.

BACKGROUND: To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma (HCC), combination with radiotherapy (RT) has emerged as a promising strategy. In preclinical studies, irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy. Hence, we investigated whether RT enhances the efficacy of anti-programmed death receptor-1 (PD-1) inhibitors in advanced HCC in real-world practice. METHODS: Between August 2018 and June 2021, 172 patients with advanced primary HCC were enrolled in the tertiary center (Zhongshan Hospital of Fudan University); 95 were treated with a combination of RT and the inhibitor of PD-1 (RT-PD1 cohort), and 77 were administered anti-PD-1 therapy (PD1 cohort). The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT. Propensity score matching for bias reduction was used to evaluate the clinical outcomes. RESULTS: Among 71 propensity-matched pairs, median progression-free survival was 5.7 months in the RT-PD1 cohort vs. 2.9 months in the PD1 cohort (P <0.001). Median overall survival was 20.9 months in the RT-PD1 cohort vs. 11.2 months in the PD1 cohort (P = 0.018). Compared with patients in the PD1 cohort, patients in the RT-PD1 cohort had significantly higher objective response rates (29/71, 40.8% vs. 14/71, 19.7%, P = 0.006) and disease control rates (44/71, 62.0% vs. 22/71, 31.0%, P <0.001). The incidences of toxic effects were not significantly different between the two cohorts. CONCLUSIONS: RT plus anti-PD-1 therapy is well tolerated. RT enhances the efficacy of anti-PD-1 therapy in patients with advanced primary HCC by improving survival outcomes without increased toxic effects.

HOXB5 promotes the progression and metastasis of osteosarcoma cells by activating the JAK2/STAT3 signalling pathway.

Objective: To investigate the involvement of the homeobox gene B5 (HOXB5) in the progression and metastasis of osteosarcoma. Methods: The expression of HOXB5 in human osteosarcoma tissues and its correlation with clinical indicators were investigated using bioinformatics analysis and immunohistochemical labelling. Human osteosarcoma cells (HOS, MG63, U2OS, and Saos-2) and normal human osteoblasts (hFOB1.19) were cultivated. The expression of HOXB5 in these cells was detected using western blotting (WB) and RT‒PCR. Two cell lines exhibiting elevated HOXB5 expression were chosen and divided into three groups: the blank group (mock), control group (control) and transfection group (shHOXB5). The transfection group was infected with lentivirus expressing shRNAs targeting HOXB5. The transfection efficiency was detected by WB. Cell proliferation suppression was measured by CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays; the percentage of apoptotic cells was determined by flow cytometry; and cell migration and invasion were detected via the Transwell chamber test. WB was utilized to determine the protein expression of genes linked to metastasis (MMP2, MMP9), apoptosis (Bax, Bcl-2), and the JAK2/STAT3 pathway (JAK2, p-JAK2, STAT3, p-STAT3). Results: In osteosarcoma tissues, HOXB5 expression was elevated and strongly correlated with distant metastasis. Silencing HOXB5 reduced the proliferation, migration and invasion of osteosarcoma cells; prevented the progression and metastasis of tumours in tumour-bearing nude mice; and reduced the activation of key proteins in the JAK2/STAT3 signalling pathway. Conclusion: Through the JAK2/STAT3 signalling pathway, HOXB5 plays a crucial role in the malignant progression of osteosarcoma and is a promising target for osteosarcoma treatment.

Human regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis.

Background: Regulatory B cells (Bregs) play a pivotal role in suppressing immune responses, yet there is still a lack of cell surface markers that can rigorously identify them. In mouse models for multiple sclerosis (MS), TIM-1 or TIGIT expression on B cells is required for maintaining self-tolerance and regulating autoimmunity to the central nervous system. Here we investigated the activities of human memory B cells that differentially express TIM-1 and TIGIT to determine their potential regulatory function in healthy donors and patients with relapsing-remitting (RR) MS. Methods: FACS-sorted TIM-1+/-TIGIT+/- memory B (memB) cells co-cultured with allogenic CD4+ T cells were analyzed for proliferation and induction of inflammatory markers using flow cytometry and cytokine quantification, to determine Th1/Th17 cell differentiation. Transcriptional differences were assessed by SMARTSeq2 RNA sequencing analysis. Results: TIM-1-TIGIT- double negative (DN) memB cells strongly induce T cell proliferation and pro-inflammatory cytokine expression. The TIM-1+ memB cells enabled low levels of CD4+ T cell activation and gave rise to T cells that co-express IL-10 with IFNγ and IL-17A or FoxP3. T cells cultured with the TIM-1+TIGIT+ double positive (DP) memB cells exhibited reduced proliferation and IFNγ, IL-17A, TNFα, and GM-CSF expression, and exhibited strong regulation in Breg suppression assays. The functional activity suggests the DP memB cells are a bonafide Breg population. However, MS DP memB cells were less inhibitory than HC DP memB cells. A retrospective longitudinal study of anti-CD20 treated patients found that post-treatment DP memB cell frequency and absolute number were associated with response to therapy. Transcriptomic analyses indicated that the dysfunctional MS-derived DP memB/Breg population exhibited increased expression of genes associated with T cell activation and survival (CD80, ZNF10, PIK3CA), and had distinct gene expression compared to the TIGIT+ or TIM-1+ memB cells. Conclusion: These findings demonstrate that TIM-1/TIGIT expressing memory B cell subsets have distinct functionalities. Co-expression of TIM-1 and TIGIT defines a regulatory memory B cell subset that is functionally impaired in MS.

Carbon flow, energy metabolic intensity and metagenomic characteristics of a Fe (III)-enhanced anerobic digestion system during treating swine wastewater.

Deep treatment and bioenergy recovery of swine wastewater (SW) are beneficial for constructing a low-carbon footprint and resource-recycling society. In this study, Fe (III) addition from 0 to 600 mg/L significantly increased the methane (CH4) content of the recovered biogas from 61.4 ±â€¯2.0 to 89.3 ±â€¯2.0 % during SW treatment in an anaerobic membrane digestion system. The specific methane yields (SMY) also increased significantly from 0.20 ±â€¯0.05 to 0.29 ±â€¯0.02 L/g COD. Fe (III) and its bio-transformed products which participated in establishing direct interspecific electron transfer (DIET), upregulated the abundance of e-pili and Nicotinamide adenine dinucleotide (NADH), enriched electroactive bacteria. The increase in cellular adenosine triphosphate (cATP) from 6583 to 14,518 ng/gVSS and electron transport system (ETS) from 1468 to 1968 mg/(g·h) promoted the intensity of energy flow and electron flow during anaerobic digestion of SW. Moreover, Fe (III) promoted the hydrolysis and acidification of organic matters, and strengthened the acetoacetic methanogenesis pathway. This study established an approach for harvesting high quality bioenergy from SW and revealed the effects and mechanisms from the view of carbon flow, energy metabolic intensity and metagenomics.

Biomechanical evaluation of reinsertion and revision screws in the subaxial cervical vertebrae.

BACKGROUND: This study aimed to evaluate the biomechanical effects of reinserted or revised subaxial cervical vertebral screws. METHODS: The first part aimed to gauge the maximum insertional torque (MIT) of 30 subaxial cervical vertebrae outfitted with 4.0-mm titanium screws. A reinsertion group was created wherein a screw was wholly removed and replaced along the same trajectory to test its maximum pullout strength (MPOS). A control group was also implemented. The second part involved implanting 4.0-mm titanium screws into 20 subaxial cervical vertebrae, testing them to failure, and then reinserting 4.5-mm revision screws along the same path to determine and compare the MIT and MPOS between the test and revision groups. RESULTS: Part I findings: No significant difference was observed in the initial insertion's maximum insertion torque (MIT) and maximum pull-out strength (MPOS) between the control and reinsertion groups. However, the MIT of the reinsertion group was substantially decreased compared to the first insertion. Moderate to high correlations were observed between the MIT and MPOS in both groups, as well as between the MIT of the first and second screw in the reinsertion group. Part II, the MIT and MPOS of the screw in the test group showed a strong correlation, while a modest correlation was observed for the revision screw used in failed cervical vertebrae screw. Additionally, the MPOS of the screw in the test group was significantly higher than that of the revision screw group. CONCLUSION: This study suggests that reinsertion of subaxial cervical vertebrae screws along the same trajectory is a viable option that does not significantly affect fixation stability. However, the use of 4.5-mm revision screws is inadequate for failed fixation cases with 4.0-mm cervical vertebral screws.

Uncertainty reduction for precipitation prediction in North America.

Large differences in projected future annual precipitation increases in North America exists across 27 CMIP6 models under four emission scenarios. These differences partly arise from weak representations of land-atmosphere interactions. Here we demonstrate an emergent constraint relationship between annual growth rates of future precipitation and growth rates of historical temperature. The original CMIP6 projections show 0.49% (SSP126), 0.98% (SSP245), 1.45% (SSP370) and 1.92% (SSP585) increases in precipitation per decade. Combining observed warming trends, the constrained results show that the best estimates of future precipitation increases are more likely to reach 0.40-0.48%, 0.83-0.93%, 1.29-1.45% and 1.70-1.87% respectively, implying an overestimated future precipitation increases across North America. The constrained results also are narrow the corresponding uncertainties (standard deviations) by 13.8-31.1%. The overestimated precipitation growth rates also reveal an overvalued annual growth rates in temperature (6.0-13.2% or 0.12-0.37°C) and in total evaporation (4.8-14.5%) by the original models' predictions. These findings highlight the important role of temperature for accurate climate predictions, which is important as temperature from current climate models' simulations often still have systematic errors.

Biomechanical Properties of Novel Porous Scaffold Core and Hollow Lateral Hole Pedicle Screws: A Comparative Study in Bama Pigs.

OBJECTIVE: Screw loosening is a common complication of internal fixation of pedicle screw. Therefore, the development of a pedicle screw with low loosening rate and high biosafety is of great clinical significance. This study aimed to investigate whether the application of a porous scaffold structure can improve the stability of pedicle screws by comparing the biomechanical properties of novel porous scaffold core pedicle screws (PSCPSs) with those of hollow lateral hole pedicle screws (HLHPSs) in a porcine lumbar spine. METHODS: Thirty-two pedicle screws of both types were implanted bilaterally into the L1-4 vertebrae of four Bama pigs, with our newly designed PSCPSs on the right and HLHPSs on the left. All the Bama pigs were sacrificed 16 weeks postoperatively, and the lumbar spine was freed into individual vertebrae. Biomechanical properties of both the pedicle screws were evaluated using pull-out tests, as well as cyclic bending and pull-out tests, while the mechanical properties were assessed using three-point bending tests. The data generated were statistically analyzed using paired-sample t-tests and two independent sample t-tests. RESULTS: We found that the maximal pull-out forces before and after cyclic bending of the PSCPSs (1161.50 ± 337.98 N and 1075.25 ± 223.33 N) were significantly higher than those of the HLHPSs (948.38 ± 194.32 N and 807.13 ± 242.75 N) (p < 0.05, p < 0.05). In 800 cycles of the bending tests, neither PSCPS nor HLHPS showed loosening or visible detachment, but their maximal pull-out forces after cyclic bending tests decreased compared to those in cycles without cyclic bending tests (7.43% and 14.89%, respectively), with no statistical significance (p > 0.05 and p > 0.05, respectively). Additionally, both screws buckled rather than broke in the three-point bending tests, with no statistically significant differences between the maximal bending load and modulus of elasticity of the two screws (p > 0.05 and p > 0.05, respectively). CONCLUSIONS: Compared with the HLHPSs, the PSCPSs have greater pull-out resistance and better fatigue tolerance with appropriate mechanical properties. Therefore, PSCPSs theoretically have significant potential for clinical applications in reducing the incidence of loosening after pedicle screw implantation.

Sustained delivery of NT-3 and curcumin augments microenvironment modulation effects of decellularized spinal cord matrix hydrogel for spinal cord injury repair.

Decellularized extracellular matrix hydrogel, especially that derived from spinal cord (DSCM hydrogel), has been actively considered as a functional biomaterial for remodeling the extracellular matrix of the native tissue, due to its unique characteristics in constructing pro-regenerative microenvironment for neural stem cells (NSCs). Furthermore, DSCM hydrogel can provide multiple binding domains to growth factors and drugs. Therefore, both exogenous neurotrophic factors and anti-inflammatory drugs are highly desired to be incorporated into DSCM hydrogel, which may synergistically modulate the complex microenvironment at the lesion site after spinal cord injury (SCI). Herein, neurotrophin-3 (NT-3) and curcumin (Cur) were integrated into DSCM hydrogel for SCI therapy. Due to different affinities to the DSCM hydrogel, NT-3 underwent a controlled release manner, while curcumin released explosively within the first 24 h, followed by rather sustained but slower release. The integration of both NT-3 and curcumin significantly enhanced NSCs proliferation and their neuronal differentiation. Meanwhile, the release of curcumin promoted macrophages polarization into anti-inflammatory subtypes, which further facilitated NSCs differentiation into neurons. The in situ injected DSCM + NT3 + Cur hydrogel exerted superior capability in alleviating the inflammatory responses in rat contused spinal cord. Compared to DSCM hydrogel alone, DSCM + NT3 + Cur hydrogel more significantly promoted the recruitment of NSCs and their neuronal differentiation at the lesion site. These outcomes favored functional recovery, as evidenced by the improved hind limb movement. Overall, the bioactive DSCM hydrogel can serve as a multifunctional carrier for cooperatively release of growth factors and drugs, which significantly benefits microenvironment regulation and nerve regeneration after SCI.

Effect of hydrothermal treatment on the rheological properties of xanthan gum.

In this study, the effect of hydrothermal treatment with different temperatures (120-180 °C) on the rheological properties of xanthan gum was evaluated. When the temperature of hydrothermal treatment was relatively low (120 °C), the rheological properties of the hydrothermally treated xanthan gum was similar to the untreated xanthan gum (pseudoplastic and solid-like/gel-like behavior). However, as the temperature of hydrothermal treatment was higher, the rheological properties of the hydrothermally treated xanthan gum changed greatly (e.g., a wider range of Newtonian plateaus in flow curves, existence of a critical frequency between the storage modulus (G') and the loss modulus (G") in the dynamic viscoelasticity measurement, variation of complex viscosity). Although the hydrothermal treatment showed little influence on the functional groups of xanthan gum, it altered the micromorphology of xanthan gum from uneven and rough lump-like to thinner and smoother flake-like. In addition, higher concentration (2 %) of hydrothermally treated xanthan gum made its viscosity close to that of the untreated xanthan gum (1 %). Besides, hydrothermal treatment also affected the effect of temperature and salt (CaCl2) adding on the rheological properties of xanthan gum. Overall, this study can provide some useful information on the rheological properties of xanthan gum after hydrothermal treatment.

Nitrogen-doped carbon dots as fluorescent probes for sensitive and selective determination of Fe3.

At present, the contamination of water resources by heavy metal ions has posed a significant threat to human survival. Therefore, it is particularly critical to develop low-cost, easy-to-use, and highly efficient heavy metal detection technologies. In this work, a fast and cost-effective fluorescent probe for nitrogen-doped carbon dots (N-CDs) was prepared using one-step hydrothermal method with citric acid (CA) as carbon source, and melamine as nitrogen source. The structural and optical characterizations of the resulting N-CDs were investigated in details. The results showed that the quantum yield of the prepared fluorescent probe was as high as 45 %, and an average fluorescence lifetime was about 7.80 ns. N-CDs have excellent water solubility and dispersibility, with an average size of 2.58 nm. N-CDs exhibited excellent specific responsiveness to Fe3+ and can be used as an effective method for detecting Fe3+ at low-concentrations (the concentrations of N-CDs as low as 0.24 µg/mL) using fluorescent probes. The linear response of the fluorescent probe N-CDs to Fe3+ was formed in the concentration range of 20-80 µM, and the detection limit was 3.18 µM. In addition, in the actual water samples analysis, the recovery rate reached 97.05-100.58 %. The prepared of N-CDs provide available Fe3+ fluorescent probes in the environment.

Structure-function relationship and biological activity of polysaccharides from mulberry leaves: A review.

Mulberry (Latin name "Morus alba L.") is a perennial deciduous tree in the family of Moraceae, widely distributed around the world. In China, mulberry is mainly distributed in the south and the Yangtze River basin. Its leaves can be harvested 3-6 times a year, which has a great resource advantage. Mulberry leaves are regarded as the homology of medicine and food traditional Chinese medicine (TCM). Polysaccharides, as its main active ingredients, have various effects, such as antioxidant, hypoglycemic, hepatoprotective, and immunomodulatory. This review summarizes the research progress in the extraction, purification, structural characterization, and structure-function relationship of polysaccharides from mulberry leaves in the last decade, hoping to provide a reference for the subsequent development and market application of polysaccharides from mulberry leaves.

One-Step Decoration of Subnanometer MoOx Clusters on Bi11VO19 Nanotubes for Visible-Light-Driven Water Oxidation.

For the sluggish reaction kinetics due to a four-electron transfer process, water oxidation is always a major obstacle to solar splitting of water to hydrogen. It remains a tough challenge to develop efficient nonnoble-metal photocatalysts for water oxidation. Herein, we decorate the host photocatalyst of Bi11VO19 nanotubes with the coatalyst of subnanometer MoOx clusters (denoted as Bi11VO19/MoOx hetero-nanotubes) via a one-step cation-exchange solvothermal reaction using Na2V6O16 nanowires as the hard template. It is observed that the morphology and microstructure of Bi11VO19/MoOx hetero-nanotubes vary with the dosage of Mo source and polyvinylpyrrolidone, as well as with the solvent composition. The optimized Bi11VO19/MoOx hetero-nanotubes significantly enhance the photooxidation of water to oxygen with visible light, delivering an oxygen production rate of 790 µmol g-1 h-1, which is 12 times that of bare Bi11VO19 nanotubes. In situ X-ray photoelectron spectroscopy and (photo)electrochemical characterization suggest that the enhanced photoactivity may be caused by the decorated cocatalyst of MoOx clusters, which extracts electrons from Bi11VO19 nanotubes, leaving an abundance of holes for water photooxidation. This work demonstrates a potential strategy to develop photocatalysts for energy conversion by constructing Bi11VO19-based nanostructures.

Recombinant human IL-37 attenuates acute cardiac allograft rejection in mice.

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.

Soft Actuator with Biomass Porous Electrode: A Strategy for Lowering Voltage and Enhancing Durability.

Electroactive artificial muscles with deformability have attracted widespread interest in the field of soft robotics. However, the design of artificial muscles with low-driven voltage and operational durability remains challenging. Herein, novel biomass porous carbon (BPC) electrodes are proposed. The nanoporous BPC enables the electrode to provide exposed active surfaces for charge transfer and unimpeded channels for ion migration, thus decreasing the driving voltage, enhancing time durability, and maintaining the actuation performances simultaneously. The proposed actuator exhibits a high displacement of 13.6 mm (bending strain of 0.54%) under 0.5 V and long-term durability of 99.3% retention after 550,000 cycles (∼13 days) without breaks. Further, the actuators are integrated to perform soft touch on a smartphone and demonstrated as bioinspired robots, including a bionic butterfly and a crawling robot (moving speed = 0.08 BL s-1). This strategy provides new insight into the design and fabrication of high-performance electroactive soft actuators with great application potential.

Tripedal DNA Walker as a Signal Amplifier Combined with a Potential-Resolved Multicolor Electrochemiluminescence Strategy for Ultrasensitive Detection of Prostate Cancer Staging Indicators.

A multicolor electrochemiluminescence (ECL) biosensor based on a closed bipolar electrode (BPE) array was proposed for the rapid and intuitive analysis of three prostate cancer staging indicators. First, [Irpic-OMe], [Ir(ppy)2(acac)], and [Ru(bpy)3]2+ were applied as blue, green, and red ECL emitters, respectively, whose mixed ECL emission colors covered the whole visible region by varying the applied voltages. Afterward, we designed a simple Mg2+-dependent DNAzyme (MNAzyme)-driven tripedal DNA walker (TD walker) to release three output DNAs. Immediately after, three output DNAs were added to the cathodic reservoirs of the BPE for incubation. After that, we found that the emission colors from the anode of the BPE changed as a driving voltage of 8.0 V was applied, mainly due to changes in the interfacial potential and faradaic currents at the two poles of the BPE. Via optimization of the experimental parameters, cutoff values of such three indicators at different clinical stages could be identified instantly with the naked eye, and standard precision swatches with multiple indicators could be prepared. Finally, in order to precisely determine the prostate cancer stage, the multicolor ECL device was used for clinical analysis, and the resulting images were then compared with standard swatches, laying the way for accurate prostate cancer therapy.

Stereotactic body radiation therapy in patients with centrally located hepatocellular carcinoma: A retrospective, single-arm, multi-center study.

Centrally located hepatocellular carcinoma (HCC) is difficult to be radically resected due to its special location close to major hepatic vessels. Thus, we aimed to assess whether stereotactic body radiation therapy (SBRT) can be an effective and safe approach for centrally located HCC. This retrospective study included 172 patients with centrally located HCC who were treated with SBRT. Overall survival (OS) was analyzed as the primary endpoint. Rates of progression-free survival (PFS), local control, intrahepatic relapse, extrahepatic metastasis and toxicities were analyzed as secondary endpoints. The OS rates of 1-, 3-, and 5-year were 97.7%, 86.7%, and 76.3%, respectively. The PFS/local control rates of 1-, 3-, and 5-year were 94.1%/98.2%, 76.8%/94.9%, and 59.3%/92.3%, respectively. The cumulative incidence of intrahepatic relapse/extrahepatic metastases of 1-, 3-, and 5-year were 3.7%/2.9%, 25.0%/7.4%, and 33.3%/9.8%, respectively. Both univariate and multivariate analyses revealed that patients received BED10 at 100 Gy or more had better OS. Radiation-related adverse events were mild to moderate according to Common Terminology Criteria for Adverse Events, and no toxicities over grade 3 were observed. Patients with centrally located HCC in our cohort who received SBRT had similar OS and PFS rates compared to those reported in literatures who received surgery with neoadjuvant or adjuvant intensity-modulated radiation therapy. These results indicate that SBRT is an effective and well-tolerated method for patients with centrally located HCC, suggesting that it may serve as a reasonable alternative treatment for these kind of patients.

Study on the Design, Synthesis, Bioactivity and Translocation of the Conjugates of Phenazine-1-carboxylic Acid and N-Phenyl Alanine Ester.

The natural pesticide phenazine-1-carboxylic acid (PCA) is known to lack phloem mobility, whereas Metalaxyl is a representative phloem systemic fungicide. In order to endow PCA with phloem mobility and also enhance its antifungal activity, thirty-two phenazine-1-carboxylic acid-N-phenylalanine esters conjugates were designed and synthesized by conjugating PCA with the active structure N-acylalanine methyl ester of Metalaxyl. All target compounds were characterized by 1H NMR, 13C NMR and HRMS. The antifungal evaluation results revealed that several target compounds exhibited moderate to potent antifungal activities against Sclerotinia sclerotiorum, Bipolaris sorokiniana, Phytophthora parasitica, Phytophthora citrophthora. In particular, compound F7 displayed excellent antifungal activity against S. sclerotiorum with an EC50 value of 6.57 µg/mL, which was superior to that of Metalaxyl. Phloem mobility study in castor bean system indicated good phloem mobility for the target compounds F1-F16. Particularly, compound F2 exhibited excellent phloem mobility; the content of compound F2 in the phloem sap of castor bean was 19.12 µmol/L, which was six times higher than Metalaxyl (3.56 µmol/L). The phloem mobility tests under different pH culture solutions verified the phloem translocation of compounds related to the "ion trap" effect. The distribution of the compound F2 in tobacco plants further suggested its ambimobility in the phloem, exhibiting directional accumulation towards the apical growth point and the root. These results provide valuable insights for developing phloem mobility fungicides mediated by exogenous compounds.