Integrative molecular and spatial analysis reveals evolutionary dynamics and tumor-immune interplay of in situ and invasive acral melanoma.

In acral melanoma (AM), progression from in situ (AMis) to invasive AM (iAM) leads to significantly reduced survival. However, evolutionary dynamics during this process remain elusive. Here, we report integrative molecular and spatial characterization of 147 AMs using genomics, bulk and single-cell transcriptomics, and spatial transcriptomics and proteomics. Vertical invasion from AMis to iAM displays an early and monoclonal seeding pattern. The subsequent regional expansion of iAM exhibits two distinct patterns, clonal expansion and subclonal diversification. Notably, molecular subtyping reveals an aggressive iAM subset featured with subclonal diversification, increased epithelial-mesenchymal transition (EMT), and spatial enrichment of APOE+/CD163+ macrophages. In vitro and ex vivo experiments further demonstrate that APOE+CD163+ macrophages promote tumor EMT via IGF1-IGF1R interaction. Adnexal involvement can predict AMis with higher invasive potential whereas APOE and CD163 serve as prognostic biomarkers for iAM. Altogether, our results provide implications for the early detection and treatment of AM.

TSPAN6 reinforces the malignant progression of glioblastoma via interacting with CDK5RAP3 and regulating STAT3 signaling pathway.

Glioblastoma is the prevailing and highly malignant form of primary brain neoplasm with poor prognosis. Exosomes derived from glioblastoma cells act a vital role in malignant progression via regulating tumor microenvironment (TME), exosomal tetraspanin protein family members (TSPANs) are important actors of cell communication in TME. Among all the TSPANs, TSPAN6 exhibited predominantly higher expression levels in comparison to normal tissues. Meanwhile, glioblastoma patients with high level of TSPAN6 had shorter overall survival compared with low level of TSPAN6. Furthermore, TSPAN6 promoted the malignant progression of glioblastoma via promoting the proliferation and metastatic potential of glioblastoma cells. More interestingly, TSPAN6 overexpression in glioblastoma cells promoted the migration of vascular endothelial cell, and exosome secretion inhibitor reversed the migrative ability of vascular endothelial cells enhanced by TSPAN6 overexpressing glioblastoma cells, indicating that TSPAN6 might reinforce angiogenesis via exosomes in TME. Mechanistically, TSPAN6 enhanced the malignant progression of glioblastoma by interacting with CDK5RAP3 and regulating STAT3 signaling pathway. In addition, TSPAN6 overexpression in glioblastoma cells enhanced angiogenesis via regulating TME and STAT3 signaling pathway. Collectively, TSPAN6 has the potential to serve as both a therapeutic target and a prognostic biomarker for the treatment of glioblastoma.

Efficacy of different indocyanine green doses in fluorescent laparoscopic cholecystectomy: A prospective, randomized, double-blind trial.

BACKGROUND AND OBJECTIVES: Intraoperative bile duct injury is a significant complication in laparoscopic cholecystectomy (LC). Near-infrared fluorescence cholangiography (NIFC) can reduce this complication. Therefore, determining the optimal indocyanine green (ICG) dosage for effective NIFC is crucial. This study aimed to determine the optimal ICG dosage for NIFC. METHODS: This was a prospective, randomized, double-blind clinical trial at a single tertiary referral center, including 195 patients randomly assigned to three groups: lower dose (0.01 mg/BMI) ICG (n = 63), medium dose (0.02 mg/BMI) ICG (n = 68), and higher dose (0.04 mg/BMI) ICG (n = 64). Surgeon satisfaction and detection rates for seven biliary structures were compared among the three dose groups. RESULTS: Demographic parameters did not significantly differ among the groups. The medium dose (72.1%) and higher dose ICG groups (70.3%) exhibited superior visualization of the common hepatic duct compared to the lower dose group (41.3%) (p < 0.001). No differences existed between the medium and higher dose groups. Similar trends were observed for the common bile duct and cystic common bile duct junction. CONCLUSIONS: In patients undergoing fluorescent laparoscopic cholecystectomy, the 0.02 mg/BMI dose of indocyanine green demonstrated better biliary structure detection rates than the 0.01 mg/BMI dose and was non-inferior to the 0.04 mg/BMI dose.

Can Robotic Arm-assisted Total Knee Arthroplasty Remain Cost-effective in Volume-based Procurement System in China? A Markov Model-based Study.

OBJECTIVE: The volume based procurement (VBP) program in China was initiated in 2022. The cost-effectiveness of robotic arm assisted total knee arthroplasty is yet uncertain after the initiation of the program. The objective of the study was to investigate the cost-effectiveness of robotic arm-assisted total knee arthroplasty and the influence of the VBP program to its cost-effectiveness in China. METHODS: The study was a Markov model-based cost-effectiveness study. Cases of primary total knee arthroplasty from January 2019 to December 2021 were included retrospectively. A Markov model was developed to simulate patients with advanced knee osteoarthritis. Manual and robotic arm-assisted total knee arthroplasties were compared for cost-effectiveness before and after the engagement of the VBP program in China. Probability and sensitivity analysis were conducted. RESULTS: Robotic arm-assisted total knee arthroplasty showed better recovery and lower revision rates before and after initiation of the VBP program. Robotic arm-based TKA was superior to manual total knee arthroplasty, with an increased effectiveness of 0.26 (16.87 vs 16.61) before and 0.52 (16.96 vs 16.43) after the application of Volume-based procurement, respectively. The procedure is more cost-effective in the new procurement system (17.13 vs 16.89). Costs of manual or robotic arm-assisted TKA were the most sensitive parameters in our model. CONCLUSION: Based on previous and current medical charging systems in China, robotic arm-assisted total knee arthroplasty is a more cost-effective procedure compared to traditional manual total knee arthroplasty. As the volume-based procurement VBP program shows, the procedure can be more cost-effective.

Influence of suspended particles and dissolved organic matters on virus enrichment in reclaimed water by two-step tangential flow ultrafiltration: Phenomena and mechanisms.

Enteric virus concentration in large-volume water samples is crucial for detection and essential for assessing water safety. Certain dissolution and suspension components can affect the enrichment process. In this study, tangential flow ultrafiltration (TFUF) was used as an enrichment method for recovering enteric virus in water samples. Interestingly, the bacteriophage MS2 recovery in reclaimed water and the reclaimed water without particles were higher than that in ultrapure water. The simulated reclaimed water experiments showed that humic acid (HA) (92.16% ± 4.32%) and tryptophan (Try) (81.50 ± 7.71%) enhanced MS2 recovery, while the presence of kaolin (Kaolin) inhibited MS2 recovery with an efficiency of 63.13% ± 11.17%. Furthermore, Atomic force microscopy (AFM) revealed that the MS2-HA cluster and the MS2-Try cluster had larger roughness values on the membrane surface, making it difficult to be eluted, whereas MS2-Kaolin cluster had compact surfaces making it difficult to be eluted. Additionally, the MS2-HA cluster is bound to the membrane by single hydrogen bond with SO, whereas both the MS2-Try cluster and the MS2-Kaolin cluster are bound to the membrane by two hydrogen bonds, making eluting MS2 challenging. These findings have potential implications for validating standardized methods for virus enrichment in water samples.

Machine learning for predicting liver and/or lung metastasis in colorectal cancer: A retrospective study based on the SEER database.

OBJECTIVE: This study aims to establish a machine learning (ML) model for predicting the risk of liver and/or lung metastasis in colorectal cancer (CRC). METHODS: Using the National Institutes of Health (NIH)'s Surveillance, Epidemiology, and End Results (SEER) database, a total of 51265 patients with pathological diagnosis of colorectal cancer from 2010 to 2015 were extracted for model development. On this basis, We have established 7 machine learning algorithm models. Evaluate the model based on accuracy, and AUC of receiver operating characteristics (ROC) and explain the relationship between clinical pathological features and target variables based on the best model. We validated the model among 196 colorectal cancer patients in Beijing Electric Power Hospital of Capital Medical University of China to evaluate its performance and universality. Finally, we have developed a network-based calculator using the best model to predict the risk of liver and/or lung metastasis in colorectal cancer patients. RESULTS: 51265 patients were enrolled in the study, of which 7864 (15.3 %) had distant liver and/or lung metastasis. RF had the best predictive ability, In the internal test set, with an accuracy of 0.895, AUC of 0.956, and AUPR of 0.896. In addition, the RF model was evaluated in the external validation set with an accuracy of 0.913, AUC of 0.912, and AUPR of 0.611. CONCLUSION: In this study, we constructed an RF algorithm mode to predict the risk of colorectal liver and/or lung metastasis, to assist doctors in making clinical decisions.

Progress of researches on mechanisms of acupuncture therapy in the treatment of lumbar disc herniation. / é’ˆç¸æ²»ç–—è °æ¤Žé—´ç›˜çªå‡ºç—‡ä½œç”¨æœºåˆ¶ç ”ç©¶è¿›å±•.

Lumbar intervertebral disc herniation (LDH) is a common and frequently-occurring disease, which usually causes lumbar and leg pain. Studies have shown that acupuncture can improve the symptoms of LDH patients. In the present paper, we summarize the progress of researches on the mechanisms of acupuncture underlying improvement of symptoms of LDH in recent 10 years from 1) delaying the intervertibral disc degeneration (by down-regulating the expressions of matrix metalloproteinase ï¼»MMPï¼½-3 and MMP-4, up-regulating the expressions of diosaccharides and polyglycoprotein, inhibiting apoptosis and promoting mitochondrial autophagy of nucleus pulposus cells, etc.), 2) maintaining spinal column stability (by relieving rachiasmus and improving lumbar flexor and extensor muscle strength, lowering the degree of polyfidus edema and fat infiltration, and restoring the biomechanics of the spine), 3) regulating inflammation (by inhibiting the production of proinflammatory factors and increasing the production of anti-inflammatory factors, etc.), 4) regulating immune response (by promoting the activity of T cells and other immune cells, lowering serum levels of MMP-3, transforming growth factor-ß1 and prostaglandin E2, raising serum levels of IgA, IgG and IgM to improve immune function ), 5) modulating neural structure and function (by promoting myelin regeneration of sciatic nerve fibers, and reducing the edema of Schwann cells' cytoplasm and mitochondria, and improving neural ultrastructure, and sensory and motor functions of peripheral nerves, etc.), 6) relieving lumbar pain (by down-regulating expression of Ca2+/calmodulin-dependent protein kinase and activation of lumbar spinal cord glial cells, blocking nociceptive signal conduction, regulating the levels of pain-related factors, etc.), and 7) improving local microcirculation. These results may provide scientific evidence for acupuncture treatment of LDH.

The Effect of Lateralization and Distalization After Grammont-Style Reverse Total Shoulder Arthroplasty.

BACKGROUND: The purpose of this study is to evaluate the relationship between multiple radiographic measures of lateralization and distalization and clinical outcome scores after reverse total shoulder arthroplasty (RTSA). METHODS: We retrospectively evaluated all RTSAs performed by the senior author between January 1, 2007, and November 1, 2017. We then evaluated the visual analog scale for pain (VAS pain), Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons (ASES) scores and complication and reoperation rates at a minimum of 2-year follow-up. We measured preoperative and postoperative (2-week) radiographs for the lateralization shoulder angle (LSA), the distalization shoulder angle (DSA), lateral humeral offset (LHO), and distance from glenoid to lateral aspect of the greater tuberosity (GLAGT). A multivariable analysis was performed evaluating the effect of the postoperative radiographic measurements on final patient reported outcomes (ASES scores, SST, VAS pain). RESULTS: The cohort included 216 shoulders from unique patients who had patient reported outcome scores available at a minimum of 2-year follow-up (average, 4.0±1.9 years) for a total follow-up rate of 70%. In the multivariable models, more lateralization (LSA) was associated with worse final ASES scores -0.52 (95% CI: -0.88 to -0.17; p=0.004), and more distalization (DSA) was associated with better final ASES scores 0.40 (95% CI: 0.11, 0.69; p=0.007). More lateralization (LSA) was associated with worse final SST scores -0.06 (95% CI: -0.11, -0.003; p=0.039). Finally, greater distalization (DSA) was associated with lower final VAS pain scores, Ratio = 0.98 (95% CI: 0.96, 1.00; p=0.021). CONCLUSION: Greater distalization and less lateralization are associated with better function and less pain after Grammont-style RTSA. If utilizing a Grammont-style implant, remaining consistent with Grammont's principles of implant placement will afford better final clinical outcomes.

Investigation of the Single-Particle Scale Structure-Activity Relationship Providing New Insights for the Development of High-Performance Batteries.

As electric vehicles, portable electronic devices, and tools have increasingly high requirements for battery energy density and power density, constantly improving battery performance is a research focus. Accurate measurement of the structure-activity relationship of active materials is key to advancing the research of high-performance batteries. However, conventional performance tests of active materials are based on the electrochemical measurement of porous composite electrodes containing active materials, polymer binders, and conductive carbon additives, which cannot establish an accurate structure-activity relationship with the physical characterization of microregions. In this review, in order to promote the accurate measurement and understanding of the structure-activity relationship of materials, the electrochemical measurement and physical characterization of energy storage materials at single-particle scale are reviewed. The potential problems and possible improvement schemes of the single particle electrochemical measurement and physical characterization are proposed. Their potential applications in single particle electrochemical simulation and machine learning are prospected. This review aims to promote the further application of single particle electrochemical measurement and physical characterization in energy storage materials, hoping to achieve 3D unified evaluation of physical characterization, electrochemical measurement, and theoretical simulation at the single particle scale to provide new inspiration for the development of high-performance batteries.

The Impact of FBN1-α5ß1 Axis in Fibro/Adipogenic Progenitor Cells (FAPCD9-) on Intramuscular Fat Content in Pigs.

Intramuscular fat (IMF) plays a crucial role in enhancing meat quality, enriching meat flavor, and overall improving palatability. In this study, Single-cell RNA sequencing was employed to analyze the longissimus dorsi (LD) obtained from Guangdong small-ear spotted pigs (GDSS, with high IMF) and Yorkshire pigs (YK, with low IMF). GDSS had significantly more Fibro/Adipogenic Progenitor (FAPs), in which the CD9 negative FAPs (FAPCD9-) having adipogenic potential, as demonstrated by in vitro assays using cells originated from mouse muscle. On the other hand, Yorkshire had more fibro-inflammatory progenitors (FIPs, marked with FAPCD9+), presenting higher expression of the FBN1-Integrin α5ß1. FBN1-Integrin α5ß1 could inhibit insulin signaling in FAPCD9-, suppressing adipogenic differentiation. Our results demonstrated that fat-type pigs possess a greater number of FAPCD9-, which are the exclusive cells in muscle capable of differentiating into adipocytes. Moreover, lean-type pigs exhibit higher expression of FBN1-Integrin α5ß1 axis, which inhibits adipocyte differentiation. These results appropriately explain the observed higher IMF content in fat-type pigs.

Lithium chloride promotes mesenchymal-epithelial transition in murine cutaneous wound healing via inhibiting CXCL9 and IGF2.

Cutaneous wound healing is a challenge in plastic and reconstructive surgery. In theory, cells undergoing mesenchymal transition will achieve re-epithelialization through mesenchymal-epithelial transition at the end of wound healing. But in fact, some pathological stimuli will inhibit this biological process and result in scar formation. If mesenchymal-epithelial transition can be activated at the corresponding stage, the ideal wound healing may be accomplished. Two in vivo skin defect mouse models and dermal-derived mesenchymal cells were used to evaluate the effect of lithium chloride in wound healing. The mesenchymal-epithelial transition was detected by immunohistochemistry staining. In vivo, differentially expressed genes were analysed by transcriptome analyses and the subsequent testing was carried out. We found that lithium chloride could promote murine cutaneous wound healing and facilitate mesenchymal-epithelial transition in vivo and in vitro. In lithium chloride group, scar area was smaller and the collagen fibres are also orderly arranged. The genes related to mesenchyme were downregulated and epithelial mark genes were activated after intervention. Moreover, transcriptome analyses suggested that this effect might be related to the inhibition of CXCL9 and IGF2, subsequent assays demonstrated it. Lithium chloride can promote mesenchymal-epithelial transition via downregulating CXCL9 and IGF2 in murine cutaneous wound healing, the expression of IGF2 is regulated by ß-catenin. It may be a potential promising therapeutic drug for alleviating postoperative scar and promoting re-epithelialization in future.

Vonoprazan is Not Inferior to Proton Pump Inhibitors in Bismuth-containing Quadruple Therapy for Helicobacter pylori Eradication: A Meta-analysis of 10 Studies From East Asia.

OBJECTIVE: To investigate the efficacy and safety of vonoprazan based bismuth-containing quadruple therapy (VBCQ) in eradicating Helicobacter pylori (Hp). MATERIALS AND METHODS: The VBCQ and the proton pump inhibitor-based bismuth-containing quadruple regimen (PBCQ) were compared by retrieving relevant studies in Pubmed, Embase, Cochrane Library, CNKI, and Wanfang data. Combined analysis was performed with risk ratio (RR) and 95% CI as effect values. RESULTS: A total of 10 studies were enrolled, including 7 randomized controlled trials and 3 cohort studies. In intention-to-treat analysis, the eradication rate of VBCQ (89.24%, 1103/1236) was significantly higher than that of PBCQ (84.03%, 1021/1215), with RR = 1.06 (95% CI: 1.03~1.10). In per-protocol analysis, the eradication rates of VBCQ and PBCQ were 92.94% (895/963) and 87.82% (829/944), respectively, with a significant difference (RR = 1.06, 95% CI: 1.03~1.09). Subgroup analysis of study design types shared similar results. VBCQ and PBCQ showed an incidence of adverse reactions of 37.30% (304/815) and 34.94% (282/807), respectively. Significant differences were not found between the two groups (RR = 1.07, 95% CI: 0.96-1.19), nor in subgroup analysis. The good compliance rates in VBCQ and PBCQ groups were 94.32% (216/229) and 95.13% (215/226), respectively, with no significant difference (RR = 0.99, 95% CI: 0.95~1.04). CONCLUSION: VBCQ has a higher eradication rate on Hp than PBCQ, while its adverse reactions and compliance are similar to PBCQ. However, we conservatively believe that in Hp eradication, the VBCQ is not inferior to PBCQ because of the small absolute difference.

Differentiation of Type 17 Mucosal-Associated Invariant T Cells in Circulation Contributes to the Severity of Sepsis.

Mucosal-associated invariant T (MAIT) cells are essential in defending against infection. Sepsis is a systemic inflammatory response to infection and a leading cause of death. The relationship between the overall competency of the host immune response and disease severity is not fully elucidated. This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RAR-related orphan receptor γt in patients with sepsis. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA-sequencing analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in patients with sepsis. Cell-culture experiments demonstrated that phosphoinositide 3-kinase-LDHA signaling was required for RAR-related orphan receptor γt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 cells in sepsis. In summary, this study reveals a new role of circulating MAIT17 in promoting sepsis severity and suggests the phosphoinositide 3-kinase-LDHA signaling as a driving force in MAIT17 responses.

Adhesion Energy-Assisted Low Contact Thermal Resistance Epoxy Resin-Based Composite.

Although intense efforts have been devoted to the development of thermally conductive epoxy resin composites, most previous works ignore the importance of the contact thermal resistance between epoxy resin composites and mating surfaces. Here, we report on epoxy resin/hexagonal boron nitride (h-BN) composites, which show low contact thermal resistance with the contacting surface by tuning adhesion energy. We found that adhesion energy increases with increasing the ratio of soybean-based epoxy resin/amino silicone oil and h-BN contents. The adhesion energy has a negative correlation with the contact thermal resistance; that is, enhancing the adhesion energy will lead to reduced contact thermal resistance. The contact thermal conductance increases with the h-BN contents and is low to 0.025 mm2·K/W for the epoxy resin/60 wt % h-BN composites, which is consistent with the theoretically calculated value. By investigating the wettability and chain dynamics of the epoxy resin/h-BN composites, we confirm that the low contact thermal resistance stems from the increased intermolecular interaction between the epoxy resin chains. The present study provides a practical approach for the development of epoxy resin composites with enhanced thermal conductivity and reduced contact thermal resistance, aiming for effective thermal management of electronics.

Enteric coronavirus nsp2 is a virulence determinant that recruits NBR1 for autophagic targeting of TBK1 to diminish the innate immune response.

Non-structural protein 2 (nsp2) exists in all coronaviruses (CoVs), while its primary function in viral pathogenicity, is largely unclear. One such enteric CoV, porcine epidemic diarrhea virus (PEDV), causes high mortality in neonatal piglets worldwide. To determine the biological role of nsp2, we generated a PEDV mutant containing a complete nsp2 deletion (rPEDV-Δnsp2) from a highly pathogenic strain by reverse genetics, showing that nsp2 was dispensable for PEDV infection, while its deficiency reduced viral replication in vitro. Intriguingly, rPEDV-Δnsp2 was entirely avirulent in vivo, with significantly increased productions of IFNB (interferon beta) and IFN-stimulated genes (ISGs) in various intestinal tissues of challenged newborn piglets. Notably, nsp2 targets and degrades TBK1 (TANK binding kinase 1), the critical kinase in the innate immune response. Mechanistically, nsp2 induced the macroautophagy/autophagy process and recruited a selective autophagic receptor, NBR1 (NBR1 autophagy cargo receptor). NBR1 subsequently facilitated the K48-linked ubiquitination of TBK1 and delivered it for autophagosome-mediated degradation. Accordingly, the replication of rPEDV-Δnsp2 CoV was restrained by reduced autophagy and excess productions of type I IFNs and ISGs. Our data collectively define enteric CoV nsp2 as a novel virulence determinant, propose a crucial role of nsp2 in diminishing innate antiviral immunity by targeting TBK1 for NBR1-mediated selective autophagy, and pave the way to develop a new type of nsp2-based attenuated PEDV vaccine. The study also provides new insights into the prevention and treatment of other pathogenic CoVs.Abbreviations: 3-MA: 3-methyladenine; Baf A1: bafilomycin A1; CoV: coronavirus; CQ: chloroquine; dpi: days post-inoculation; DMVs: double-membrane vesicles; GABARAP: GABA type A receptor-associated protein; GFP: green fluorescent protein; GIGYF2: GRB10 interacting GYF protein 2; hpi: hours post-infection; IFA: immunofluorescence assay; IFIH1: interferon induced with helicase C domain 1; IFIT2: interferon induced protein with tetratricopeptide repeats 2; IFITM1: interferon induced transmembrane protein 1; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISGs: interferon-stimulated genes; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAVS: mitochondrial antiviral signaling protein; NBR1: NBR1 autophagy cargo receptor; nsp2: non-structural protein 2; OAS1: 2'-5'-oligoadenylate synthetase 1; PEDV: porcine epidemic diarrhea virus; PRRs: pattern recognition receptors; RIGI: RNA sensor RIG-I; RT-qPCR: reverse transcription quantitative polymerase chain reaction; SQSTM1: sequestosome 1; TBK1: TANK binding kinase 1; TCID50: 50% tissue culture infectious doses; VSV: vesicular stomatitis virus.

hsa_circ_0007919 promotes pancreatic cancer metastasis by modulating Sp1-mediated THBS1 transcription.

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second-generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT-PCR and Kaplan-Meier survival curves. Gain- and loss-of-function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC.

Light-induced giant enhancement of nonreciprocal transport at KTaO3-based interfaces.

Nonlinear transport is a unique functionality of noncentrosymmetric systems, which reflects profound physics, such as spin-orbit interaction, superconductivity and band geometry. However, it remains highly challenging to enhance the nonreciprocal transport for promising rectification devices. Here, we observe a light-induced giant enhancement of nonreciprocal transport at the superconducting and epitaxial CaZrO3/KTaO3 (111) interfaces. The nonreciprocal transport coefficient undergoes a giant increase with three orders of magnitude up to 105 A-1 T-1. Furthermore, a strong Rashba spin-orbit coupling effective field of 14.7 T is achieved with abundant high-mobility photocarriers under ultraviolet illumination, which accounts for the giant enhancement of nonreciprocal transport coefficient. Our first-principles calculations further disclose the stronger Rashba spin-orbit coupling strength and the longer relaxation time in the photocarrier excitation process, bridging the light-property quantitative relationship. Our work provides an alternative pathway to boost nonreciprocal transport in noncentrosymmetric systems and facilitates the promising applications in opto-rectification devices and spin-orbitronic devices.

A Radical-Generating Probe to Release Free Fluorophores and Identify Artemisinin-Sensitive Cancer Cells.

The smart light-up probes have been extensively developed to image various enzymes and other bioactive molecules. Upon activation, these probes result in light-up fluorophores that exist in a protein-bound or a free form. The difference between these two forms has not yet been reported. Here, we present a pair of smart light-up probes that generate a protein-bound fluorophore and a free fluorophore upon activation by heme. Probe 8 generated a radical-attached fluorophore that predominantly existed in the free form, while probe 10 generated an α,ß-unsaturated ketone-attached fluorophore that showed extensive labeling of proteins. In live-cell imaging, probe 8 showed greater fluorescence intensity than probe 10 when low concentrations (0.1-5 µM) of the probes were used, but probe 8 was less fluorescent than probe 10 when the concentrations of the probes were high (10 µM). Finally, probe 8 was used to reflect the activation level of the endoperoxide bond in cancer cells and to effectively distinguish ART-sensitive cancer cells from ART-insensitive ones.

Construction of the single-diamond-structured titania scaffold-Recreation of the holy grail photonic structure.

As one of the most stunning biological nanostructures, the single-diamond (SD) surface discovered in beetles and weevils exoskeletons possesses the widest complete photonic bandgap known to date and is renowned as the "holy grail" of photonic materials. However, the synthesis of SD is difficult due to its thermodynamical instability compared to the energetically favoured bicontinuous double diamond and other easily formed lattices; thus, the artificial fabrication of SD has long been a formidable challenge. Herein, we report a bottom-up approach to fabricate SD titania networks via a one-pot cooperative assembly scenario employing the diblock copolymer poly(ethylene oxide)-block-polystyrene as a soft template and titanium diisopropoxide bis(acetylacetonate) as an inorganic precursor in a mixed solvent, in which the SD scaffold was obtained by kinetically controlled nucleation and growth in the skeletal channels of the diamond minimal surface formed by the polymer matrix. Electron crystallography investigations revealed the formation of tetrahedrally connected SD frameworks with the space group Fd [Formula: see text] m in a polycrystalline anatase form. A photonic bandgap calculation showed that the resulting SD structure has a wide and complete bandgap. This work solves the complex synthetic enigmas and offers a frontier in hyperbolic surfaces, biorelevant materials, next-generation optical devices, etc.

Histological Changes of Porcine Animal Skin with Micro-focused Ultrasound.

BACKGROUND: As a noninvasive alternative therapy, microfocused ultrasound (MFU) has become a research hotspot in recent years for its potential to enhance skin laxity. While several clinical studies have explored the effects of MFU on improving skin laxity, there is limited literature available on the histological changes resulting from MFU treatments. It has been established that the skin structure and composition of the Bama miniature pigs closely resembles that of humans, including collagen content, type I collagen distribution, and elastin distribution. METHODS: This study primarily focuses on examining the histological alterations in the skin tissue of Bama miniature pigs following MFU application. We also selected some typical clinical photographs of patients treated with MFU and compared the clinical effects with histological changes observed in porcine skin. The MFU device utilized in this study incorporates ultra-pulse technology and large focal area technology. RESULTS: Following the standard operating procedures provided by the manufacturer, different handles were used in different skin area of pigs. Biopsies were obtained immediately after treatment and 1 month after treatment. Significant histological changes were observed in the Bama miniature pigs skin, including collagen contraction and fragmentation, dilation and congestion of superficial dermal capillaries immediately after MFU treatment; dermal thickening, increased thickness and density of collagen fibers, elevated levels of elastin and type I collagen, as well as thickened fiber septa in the adipose layer 1 month later. These histological results corresponded to clinical findings in human, such as facial redness and swelling immediately after treatment, and improvement in facial relaxation after approximately 1 month after treatment. CONCLUSION: Collectively, these histological findings provide valuable evidence supporting the clinical application of MFU for enhancing skin laxity. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .