A vascular endothelial growth factor-loaded chitosanhyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke.

Adipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which are composed of hyaluronic acid and chitosan, exhibit excellent biocompatibility and biodegradability, making them promising candidates as cell carriers. Vascular endothelial growth factor is a crucial regulatory factor for stem cells. Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells, thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke. Here, we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells. Subsequently, we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemia-reperfusion injury. When loaded with adipose-derived stem cells, this vascular endothelial growth factor-loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology. Further in vivo experiments revealed that this vascular endothelial growth factor-loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells, leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion. It also helped maintain mitochondrial integrity and axonal morphology, greatly improving rat motor function and angiogenesis. Therefore, utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.

Aberrant functional connectivity of the globus pallidus in the modulation of the relationship between childhood trauma and major depressive disorder.

BACKGROUND: Childhood trauma plays a crucial role in the dysfunctional reward circuitry in major depressive disorder (MDD). We sought to explore the effect of abnormalities in the globus pallidus (GP)-centric reward circuitry on the relationship between childhood trauma and MDD. METHODS: We conducted seed-based dynamic functional connectivity (dFC) analysis among people with or without MDD and with or without childhood trauma. We explored the relationship between abnormal reward circuitry, childhood trauma, and MDD. RESULTS: We included 48 people with MDD and childhood trauma, 30 people with MDD without childhood trauma, 57 controls with childhood trauma, and 46 controls without childhood trauma. We found that GP subregions exhibited abnormal dFC with several regions, including the inferior parietal lobe, thalamus, superior frontal gyrus (SFG), and precuneus. Abnormal dFC in these GP subregions showed a significant correlation with childhood trauma. Moderation analysis revealed that the dFC between the anterior GP and SFG, as well as between the anterior GP and the precentral gyrus, modulated the relationship between childhood abuse and MDD severity. We observed a negative correlation between childhood trauma and MDD severity among patients with lower dFC between the anterior GP and SFG, as well as higher dFC between the anterior GP and precentral gyrus. This suggests that reduced dFC between the anterior GP and SFG, along with increased dFC between the anterior GP and precentral gyrus, may attenuate the effect of childhood trauma on MDD severity. LIMITATIONS: Cross-sectional designs cannot be used to infer causality. CONCLUSION: Our findings underscore the pivotal role of reward circuitry abnormalities in MDD with childhood trauma. These abnormalities involve various brain regions, including the postcentral gyrus, precentral gyrus, inferior parietal lobe, precuneus, superior frontal gyrus, thalamus, and middle frontal gyrus. CLINICAL TRIAL REGISTRATION: ChiCTR2300078193.

Major depressive disorder and perceived social support: Moderated mediation model of security and brain dysfunction.

Low social support increases the risk of Major depressive disorder (MDD), yet its effects on brain function are unclear. Thirty-two MDD patients with low social support, 52 with high social support, and 54 healthy controls were recruited. We investigated regional brain activity in MDD patients with low social support using resting-state functional Magnetic Resonance Imaging, employing measures such as degree centrality (DC), regional homogeneity, amplitude of low-frequency fluctuations, and fractional amplitude of low-frequency fluctuations. Abnormal regions identified in these analyses were selected as regions of interest for functional connectivity (FC) analysis. We then explored relationships among social support, brain dysfunction, MDD severity, and insecurity using partial correlation and moderated mediation models. Our findings reveal that MDD patients with low social support show decreased DC in the right superior temporal pole and right medial geniculate nucleus, coupled with increased FC between the right superior temporal pole and right inferior temporal gyrus, and the right supramarginal gyrus compared to those with high social support. Furthermore, the DC of the right medial geniculate nucleus positively correlates with social support, while the FC between the right superior temporal pole and right supramarginal gyrus negatively correlates with both social support and subjective support. Additionally, a moderated mediation model demonstrates that the FC between the right superior temporal pole and right supramarginal gyrus mediates the relationship between social support and depression severity, with security moderating this mediation. These findings underscore the impact of low social support on brain function and depression severity in MDD patients.

Endosome mediated nucleocytoplasmic trafficking and endomembrane allocation is crucial to polyglutamine toxicity.

Aggregation of aberrant proteins is a common pathological hallmark in neurodegeneration such as polyglutamine (polyQ) and other repeat-expansion diseases. Here through overexpression of ataxin3 C-terminal polyQ expansion in Drosophila gut enterocytes, we generated an intestinal obstruction model of spinocerebellar ataxia type3 (SCA3) and reported a new role of nuclear-associated endosomes (NAEs)-the delivery of polyQ to the nucleoplasm. In this model, accompanied by the prominently increased RAB5-positive NAEs are abundant nucleoplasmic reticulum enriched with polyQ, abnormal nuclear envelope invagination, significantly reduced endoplasmic reticulum, indicating dysfunctional nucleocytoplasmic trafficking and impaired endomembrane organization. Consistently, Rab5 but not Rab7 RNAi further decreased polyQ-related NAEs, inhibited endomembrane disorganization, and alleviated disease model. Interestingly, autophagic proteins were enriched in polyQ-related NAEs and played non-canonical autophagic roles as genetic manipulation of autophagic molecules exhibited differential impacts on NAEs and SCA3 toxicity. Namely, the down-regulation of Atg1 or Atg12 mitigated while Atg5 RNAi aggravated the disease phenotypes both in Drosophila intestines and compound eyes. Our findings, therefore, provide new mechanistic insights and underscore the fundamental roles of endosome-centered nucleocytoplasmic trafficking and homeostatic endomembrane allocation in the pathogenesis of polyQ diseases.

Early detection and stratification of colorectal cancer using plasma cell-free DNA fragmentomic profiling.

Timely accurate and cost-efficient detection of colorectal cancer (CRC) is of great clinical importance. This study aims to establish prediction models for detecting CRC using plasma cell-free DNA (cfDNA) fragmentomic features. Whole-genome sequencing (WGS) was performed on cfDNA from 620 participants, including healthy individuals, patients with benign colorectal diseases and CRC patients. Using WGS data, three machine learning methods were compared to build prediction models for the stratification of CRC patients. The optimal model to discriminate CRC patients of all stages from healthy individuals achieved a sensitivity of 92.31% and a specificity of 91.14%, while the model to separate early-stage CRC patients (stage 0-II) from healthy individuals achieved a sensitivity of 88.8% and a specificity of 96.2%. Additionally, the cfDNA fragmentation profiles reflected disease-specific genomic alterations in CRC. Overall, this study suggests that cfDNA fragmentation profiles may potentially become a noninvasive approach for the detection and stratification of CRC.

Epitaxial Growth of Two-Dimensional MoO2-MoSe2 Metal-Semiconductor Heterostructures for Schottky Diodes.

The metal-semiconductor interface fabricated by conventional methods often suffers from contamination, degrading transport performance. Herein, we propose a one-pot chemical vapor deposition (CVD) process to create a two-dimensional (2D) MoO2-MoSe2 heterostructure by growing MoO2 seeds under a hydrogen environment, followed by depositing MoSe2 on the surface and periphery. The ultraclean interface is verified by cross-sectional scanning transmission electron microscopy and photoluminescence. Along with the high work function of semimetallic MoO2 (Ef = -5.6 eV), a high-rectification Schottky diode is fabricated based on this heterostructure. Furthermore, the Schottky diode exhibits an excellent photovoltaic effect with a high open-circuit voltage of 0.26 eV and ultrafast photoresponse, owing to the naturally formed metal-semiconductor contact with suppressed pinning effect. Our method paves the way for the fabrication of an ultraclean 2D metal-semiconductor interface, without defects or contamination, offering promising prospects for future nanoelectronics.

XRCC1 mediates PARP1- and PAR-dependent recruitment of PARP2 to DNA damage sites.

Poly-ADP-ribose polymerases 1 and 2 (PARP1 and PARP2) are crucial sensors of DNA-strand breaks and emerging cancer therapy targets. Once activated by DNA breaks, PARP1 and PARP2 generate poly-ADP-ribose (PAR) chains on themselves and other substrates to promote DNA single-strand break repair (SSBR). PARP1 can be activated by diverse DNA lesions, whereas PARP2 specifically recognizes 5' phosphorylated nicks. They can be activated independently and provide mutual backup in the absence of the other. However, whether PARP1 and PARP2 have synergistic functions in DNA damage response remains elusive. Here, we show that PARP1 and the PAR chains generated by PARP1 recruit PARP2 to the vicinity of DNA damage sites through the scaffold protein XRCC1. Using quantitative live-cell imaging, we found that loss of XRCC1 markedly reduces irradiation-induced PARP2 foci in PARP1-proficient cells. The central BRCT domain (BRCT1) of XRCC1 binds to the PAR chain, while the C-terminal BRCT domain (BRCT2) of XRCC1 interacts with the catalytic domain of PARP2, facilitating its localization near the breaks. Together, these findings unveil a new function of XRCC1 in augmenting PARP2 recruitment in response to PARP1 activation and explain why PARP1, but not PARP2, is aggregated and hyperactivated in XRCC1-deficient cells.

Leptin combined with withaferin A boost posthemorrhagic neurogenesis via activation of STAT3/SOCS3 pathway.

Neurogenesis as a potential strategy to improve the consequences of intracerebral hemorrhage (ICH). The current study investigates the effects of withaferin A (WFA) in combination with leptin (LEP) on ICH and neurogenesis mechanisms. LEP levels were dramatically reduced on days 7 and 14 following ICH insults in mice, but continuous WFA therapy significantly improved the potency of intrinsic LEP on day 14 after ICH. Furthermore, WFA combined with LEP enhances intrinsic neurogenesis and lessen motor deficits and long-term cognitive outcomes after ICH. In parallel, leptin deficiency in ob/ob mice limits enhancement of neurogenesis following ICH in response to WFA combined with LEP treatment. Importantly, the functional recovery conferred by WFA combined with LEP after ICH was inhibited by neurogenesis suppression. Mechanistically, this study unveiled that the signal transducer and activator of transcription-3 (STAT3) / suppressor of cytokine signaling-3 (SOCS3) pathway is a critical signaling pathway through which WFA combined with LEP treatment promotes intrinsic neurogenesis after ICH. Collectively, the results of this study elucidate the neuroprotective effects of WFA and LEP in ICH, and highlight a potential approach for ICH cell therapy.

Study on the bioactive ingredients and mechanism of Huangqi against diabetic retinopathy based on network pharmacology and experimental verification.

BACKGROUND: Diabetic retinopathy (DR) is one of the most well-known microvascular complications of diabetes mellitus. As a traditional Chinese medicine, Huangqi (HQ), has been used for treating DR for a long time. However, its anti-DR active ingredients and mechanism are still unknown. Therefore, we designed this study to explore the active components and mechanism of HQ against DR via network pharmacology analysis. METHODS: The ingredients of HQ, and potential targets of HQ and DR were obtained from public databases. We used the protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment, and Gene Ontology (GO) analysis to identify core targets and pathways of HQ against DR. Finally, molecular docking and vitro experiments were applied to validate our results. RESULTS: A total of 34 potential targets of HQ against DR were obtained. Based on PPI network, VEGFA, PTGS2, Interleukin-6 (IL-6), and CCL2 were considered as core targets. GO analysis involved 692 biological processes, 21 cellular components, and 35 molecular functions. KEGG enrichment analysis manifested that the anti-DR effect of HQ was mainly mediated via the AGE-RAGE signaling pathway in diabetic complications. The molecular docking results indicated that kaempferol had higher affinity with CCL2, IL-6, VEGFA, and PTGS2. The vitro experiments showed that the mRNA expressions of CCL2, IL-6, VEGFA, and PTGS2 in ARPE-19 cells were differentially decreased after kaempferol treatment. CONCLUSION: This study preliminarily unveiled that the therapeutic efficacy of HQ against DR might be attributed to the reduced expression of CCL2, IL-6, VEGFA, and PTGS2.

Ultrasensitive and Highly Selective Detection of Staphylococcus aureus at the Single-Cell Level Using Bacteria-Imprinted Polymer and Vancomycin-Conjugated MnO2 Nanozyme.

Pathogenic bacterial infections, even at extremely low concentrations, pose significant threats to human health. However, the challenge persists in achieving high-sensitivity bacterial detection, particularly in complex samples. Herein, we present a novel sandwich-type electrochemical sensor utilizing bacteria-imprinted polymer (BIP) coupled with vancomycin-conjugated MnO2 nanozyme (Van@BSA-MnO2) for the ultrasensitive detection of pathogenic bacteria, exemplified by Staphylococcus aureus (S. aureus). The BIP, in situ prepared on the electrode surface, acts as a highly specific capture probe by replicating the surface features of S. aureus. Vancomycin (Van), known for its affinity to bacterial cell walls, is conjugated with a Bovine serum albumin (BSA)-templated MnO2 nanozyme through EDC/NHS chemistry. The resulting Van@BSA-MnO2 complex, serving as a detection probe, provides an efficient catalytic platform for signal amplification. Upon binding with the captured S. aureus, the Van@BSA-MnO2 complex catalyzes a substrate reaction, generating a current signal proportional to the target bacterial concentration. The sensor displays remarkable sensitivity, capable of detecting a single bacterial cell in a phosphate buffer solution. Even in complex milk matrices, it maintains outstanding performance, identifying S. aureus at concentrations as low as 10 CFU mL-1 without requiring intricate sample pretreatment. Moreover, the sensor demonstrates excellent selectivity, particularly in distinguishing target S. aureus from interfering bacteria of the same genus at concentrations 100-fold higher. This innovative method, employing entirely synthetic materials, provides a versatile and low-cost detection platform for Gram-positive bacteria. In comparison to existing nanozyme-based bacterial sensors with biological recognition materials, our assay offers distinct advantages, including enhanced sensitivity, ease of preparation, and cost-effectiveness, thereby holding significant promise for applications in food safety and environmental monitoring.

Steam Explosion-Assisted Extraction of Polysaccharides from Pleurotus eryngii and Its Influence on Structural Characteristics and Antioxidant Activity.

Pleurotus eryngii (PE) has been sought after for its various health benefits and high content of phenolic compounds. This study explored the feasibility of steam explosion (SE)-assisted extraction of polysaccharides with high antioxidant capacities from PE. An orthogonal experimental design (OED) was used to optimize the SE-assisted extraction of PE. The influence of the optimized SE-assisted extraction on the physicochemical properties of PE polysaccharides was determined by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), monosaccharide compositional analysis and antioxidant capacity assays. Under optimal SE conditions, SE-assisted extraction increased the polysaccharide yield by 138% compared to extraction without SE-assistance. In addition, SEM demonstrated that SE-assisted extraction markedly altered the spatial structure of Pleurotus eryngii polysaccharides (PEP), and monosaccharide compositional analysis revealed that this pretreatment significantly increased the proportions of some monosaccharides, such as glucose, rhamnose and arabinose, in the isolated PEP. FTIR spectra indicated no change in the major chemical functional groups of PEP. PEP extracted by SE-assisted extraction had significantly increased free radical scavenging and antioxidant capacities. In conclusion, SE-assisted extraction appears to be a novel polysaccharide extraction technology, which markedly increases extraction yields and efficiency and can increase the biological activity of polysaccharide extracts.

Inactive Parp2 causes Tp53-dependent lethal anemia by blocking replication-associated nick ligation in erythroblasts.

PARP1&2 enzymatic inhibitors (PARPi) are promising cancer treatments. But recently, their use has been hindered by unexplained severe anemia and treatment-related leukemia. In addition to enzymatic inhibition, PARPi also trap PARP1&2 at DNA lesions. Here, we report that unlike Parp2 -/- mice, which develop normally, mice expressing catalytically-inactive Parp2 (E534A, Parp2 EA/EA ) succumb to Tp53- and Chk2 -dependent erythropoietic failure in utero , mirroring Lig1 -/- mice. While DNA damage mainly activates PARP1, we demonstrate that DNA replication activates PARP2 robustly. PARP2 is selectively recruited and activated by 5'-phosphorylated nicks (5'p-nicks) between Okazaki fragments, typically resolved by Lig1. Inactive PARP2, but not its active form or absence, impedes Lig1- and Lig3-mediated ligation, causing dose-dependent replication fork collapse, particularly harmful to erythroblasts with ultra-fast forks. This PARylation-dependent structural function of PARP2 at 5'p-nicks explains the detrimental effects of PARP2 inhibition on erythropoiesis, revealing the mechanism behind the PARPi-induced anemia and leukemia, especially those with TP53/CHK2 loss. Significance: This work shows that the hematological toxicities associated with PARP inhibitors stem not from impaired PARP1 or PARP2 enzymatic activity but rather from the presence of inactive PARP2 protein. Mechanistically, these toxicities reflect a unique role of PARP2 at 5'-phosphorylated DNA nicks during DNA replication in erythroblasts.

Analyzing omics data based on sample network.

Identifying valuable features from complex omics data is of great significance for disease diagnosis study. This paper proposes a new feature selection algorithm based on sample network (FS-SN) to mine important information from omics data. The sample network is constructed according to the sample neighbor relationship at the molecular (feature) expression level, and the distinguishing ability of the feature is evaluated based on the topology of the sample network. The sample network established on a feature with a strong discriminating ability tends to have many edges between the same group samples and few edges between the different group samples. At the same time, FS-SN removes redundant features according to the gravitational interaction between features. To show the validation of FS-SN, it was compared on ten public datasets with ERGS, mRMR, ReliefF, ATSD-DN, and INDEED which are efficient in omics data analysis. Experimental results show that FS-SN performed better than the compared methods in accuracy, sensitivity and specificity in most cases. Hence, FS-SN making use of the topology of the sample network is effective for analyzing omics data, it can identify key features that reflect the occurrence and development of diseases, and reveal the underlying biological mechanism.

Baking releases microplastics from polyethylene terephthalate bakeware as detected by optical photothermal infrared and quantum cascade laser infrared.

The use of plastic bakeware is a potential source of human exposure to microplastics (MPs). However, characterizing MPs remains a challenge. This study aims to employ optical photothermal infrared (O-PTIR) and quantum cascade laser infrared (QCL-IR) technology to characterise polyethylene terephthalate (PET) MPs shed from PET bakeware during the baking process. The bakeware, filled with ultrapure water, underwent baking cycles at 220 °C for 20 min, 60 min, and three consecutive cycles of 60 min each. Subsequently, particles present in the ultrapure water were collected using an Al2O3 filter. O-PTIR and QCL-IR were used to characterise PET MPs collected from the filtration. Analysis revealed that QCL-IR spectra exhibited broader absorption peaks, compared to O-PTIR. Notably, MP spectra obtained from both techniques displayed common absorption peaks around 1119, 1623, 1341 and 1725 cm-1. The dominant size of PET MPs detected by O-PTIR and QCL-IR was 1-3 µm and 5-20 µm, respectively. The quantity of identified PET MPs using O-PTIR was 18 times greater than that with QCL-IR, which was attributed to variations in spatial resolution, sampling methods for spectra collection, and data analysis employed by the two methods. Importantly, findings from both techniques highlighted a notably large quantity of MPs released from PET bakeware, particularly evident after 3 cycles of 60 min of baking, suggesting a substantial increase in the potential ingestion of MPs, especially in scenarios involving extended baking durations. The research outcomes will guide consumers on minimizing the intake of microplastics by using PET bakeware for shorter baking time. Additionally, the study will yield valuable insights into the application of O-PTIR and QCL-IR for MPs detection, potentially inspiring advancements in MPs detection methodologies through cutting-edge technologies.

Diagnostic Performance of Carotid Ring Sign on CT-Angiography in Internal Carotid True Occlusion.

BACKGROUND: To differentiate between pseudo occlusion (PO) and true occlusion (TO) of internal carotid artery (ICA) is important in thrombectomy treatment planning for patients with acute ischemic stroke. Although delayed contrast filling has been differentiated carotid PO from TO, its application has been limited by the implementations of multiphasic computed tomography angiography. In this study, we hypothesized that carotid ring sign, which is readily acquired from single-phasic CTA, can sufficiently differentiate carotid TO from PO. METHODS: One thousand four hundred and twenty patients with anterior circulation stroke receiving endovascular therapy were consecutively recruited through a hospital- and web-based registry. Two hundred patients with nonvisualization of the proximal ICA were included in the analysis after a retrospective screening. Diagnosis of PO or TO of the cervical segment of ICA was made based on digital subtraction angiography. Diagnostic performances of carotid ring sign on arterial-phasic CTA and delayed contrast filling on multiphasic computed tomography angiography were evaluated and compared. RESULTS: One-hundred twelve patients had ICA PO and 88 had TO. Carotid ring sign was more common in patients with TO (70.5% versus 6.3%; P<0.001), whereas delayed contrast filling was more common in PO (94.9% versus 7.7%; P<0.001). The sensitivity and specificity of carotid ring sign in diagnosing carotid TO were 0.70 and 0.94, respectively, whereas sensitivity and specificity of delayed contrast filling was 0.95 and 0.92 in judging carotid PO. CONCLUSIONS: Carotid ring sign is a potent imaging marker in diagnosing ICA TO. Carotid ring sign could be complementary to delayed contrast filling sign in differentiating TO from PO, in particular in centers with only single-phasic CTA.

Smart windows based on ultraviolet-B persistent luminescence phosphors for bacterial inhibition and food preservation.

Herein, ultraviolet B (UVB) persistent luminescence phosphors containing SrAl12O19: Ce3+, Sc3+ nanoparticles were reported. Thermoluminescence (TL) spectrum analysis reveals that the shallow trap induced by Sc3+ co-doping plays an important role in photoluminescence persistent luminescence (PersL) development, while the deep trap dominates the generation of optical stimulated luminescence (OSL). Owing the appearance of deep trap, the OSL is observed under light (700 nm - 900 nm) excitation. UVB luminescence exerts good bactericidal effects on pathogenic bacteria involved in the process of food spoilage. Thus, the smart window with SrAl12O19: Ce3+, Sc3+/PDMS produces UVB PersL to efficiently inactivate Escherichia coli and Staphylococcus aureus. In addition, the presence of the smart window delays the critical point of pork decay, and greatly reduces the time of pork spoilage. It maximizes the convenience of eradicating bacteria and preserving food, thus offering a fresh perspective on the use of UV light for food sterilization and preservation.

Circ_0007351 Exerts an Oncogenic Role In Colorectal Cancer Depending on the Modulation of the miR-5195-3p/GPRC5A Cascade.

Circular RNAs (circRNAs) exert critical functions in colorectal cancer development. In this work, we wanted to elucidate the functional role and regulatory mechanism of circ_0007351 in colorectal cancer. For quantification of circ_0007351, microRNA (miR)-5195-3p and G Protein-coupled receptor class C group 5 member A (GPRC5A), a qRT-PCR, immunoblotting or immunohistochemistry assay was performed. Effects of circ_0007351/miR-5195-3p/GPRC5A cascade were evaluated by determining cell viability, proliferation, colony formation, motility, and invasion. Relationships among variables were assessed by dual-luciferase reporter assay. Animal studies were performed to evaluate circ_0007351's function in the growth of xenograft tumors. Circ_0007351 was markedly up-regulated in colorectal cancer tissues and cells. Down-regulation of circ_0007351 hindered cell growth, migration and invasiveness. Also, circ_0007351 depletion exerted a suppressive function in colorectal cell xenograft growth in vivo. Mechanistically, circ_0007351 sponged miR-5195-3p to sequester miR-5195-3p. Reduction of available miR-5195-3p neutralized the effects of circ_0007351 down-regulation on cell phenotypes. MiR-5195-3p directly targeted and inhibited GPRC5A. Circ_0007351 regulated GPRC5A expression by sponging miR-5195-3p. Moreover, the effects of circ_0007351 down-regulation on cell functional phenotypes were due to in part the reduction of GPRC5A expression. Our findings show that circ_0007351 down-regulation impedes proliferation, motility, and invasiveness in colorectal cancer cells at least in part via the regulation of the miR-5195-3p/GPRC5A cascade, highlighting that circ_0007351 inhibition may have a potential therapeutic value for colorectal cancer.

Low Temperature Synthesis of 2D p-Type α-In2Te3 with Fast and Broadband Photodetection.

2D A 2 III B 3 VI ${\mathrm{A}}_2^{{\mathrm{III}}}{\mathrm{B}}_3^{{\mathrm{VI}}}$ compounds (A = Al, Ga, In, and B = S, Se, and Te) with intrinsic structural defects offer significant opportunities for high-performance and functional devices. However, obtaining 2D atomic-thin nanoplates with non-layered structure on SiO2/Si substrate at low temperatures is rare, which hinders the study of their properties and applications at atomic-thin thickness limits. In this study, the synthesis of ultrathin, non-layered α-In2Te3 nanoplates is demonstrated using a BiOCl-assisted chemical vapor deposition method at a temperature below 350 °C on SiO2/Si substrate. Comprehensive characterization results confirm the high-quality single crystal is the low-temperature cubic phase α-In2Te3 , possessing a noncentrosymmetric defected ZnS structure with good second harmonic generation. Moreover, α-In2Te3 is revealed to be a p-type semiconductor with a direct and narrow bandgap value of 0.76 eV. The field effect transistor exhibits a high mobility of 18 cm2 V-1 s-1, and the photodetector demonstrates stable photoswitching behavior within a broadband photoresponse from 405 to 1064 nm, with a satisfactory response time of τrise = 1 ms. Notably, the α-In2Te3 nanoplates exhibit good stability against ambient environments. Together, these findings establish α-In2Te3 nanoplates as promising candidates for next-generation high-performance photonics and electronics.

Strategically reducing carbapenem-resistant Acinetobacter baumannii through PDCA cycle-driven antibiotic management.

PURPOSE: With the escalating global challenge of antibiotic resistance, particularly the resistance rate of Acinetobacter baumannii, the need to rationalize carbapenem antibiotic use in clinical settings has become paramount. Our study tapped into a fishbone diagram to uncover the irrationalities in applying these antibiotics and highlight potential influencing factors. METHODS: Based on these analyses, we initiated targeted intervention strategies. A PDCA cycle-based scientific management approach was implemented through the combined efforts of our antimicrobial stewardship team and relevant departments. RESULTS: Our study showed a significant post-intervention increase in the rational use of carbapenem antibiotics (P < 0.01) and a concurrent decrease in the detection of carbapenem-resistant Acinetobacter baumannii. CONCLUSION: Our findings underscore that carbapenem usage can be effectively minimized with the continuous refinements offered by the PDCA cycle, leading to a reduction in multidrug-resistant bacteria, thus fostering rational drug use in healthcare.

Clinical application of convolutional neural network for mass analysis on mammograms.

Background: The detection of masses on mammogram represents one of the earliest signs of a malignant breast cancer. However, masses may be hard to detect due to dense breast tissue, leading to false negative results. In this study, we aimed to explore the clinical application of the convolutional neural network (CNN)-based deep learning (DL) system constructed in our previous work as an objective and accurate tool for breast cancer screening and diagnosis in Asian women. Methods: This retrospective analysis included 324 patients with masses detected on mammograms at Shenzhen People's Hospital between April and December 2019. (I) Detection: images were independently analyzed by two junior radiologists who were blinded to relative results. Then, a senior radiologist analyzed the images after reviewing all the relevant information as the reference. (II) Classification: masses were classified by the same two junior radiologists and in consensus by two other seniors. Images were also input into the DL system. The sensitivity of detection by junior radiologists and the DL system, effects of different factors [breast density; patient age; morphology, margin, size, breast imaging reporting and data system (BI-RADS) category of the mass] on detection, the accuracy, sensitivity, and specificity of classification, and the area under the receiver operating characteristic (ROC) curve (AUC), were evaluated. Results: A total of 618 masses were detected. The detection sensitivity of the two junior radiologists [78.0% (482/618) and 84.0% (519/618), respectively] was lower than that of the DL system [86.2% (533/618)]. Breast density significantly affected the detection by two junior radiologists (both P=0.030), but not by the DL system (P=0.385). The AUC for classifying masses as negative (BI-RADS 1, 2, 3) or positive (BI-RADS 4A, 4B, 4C, 5) for the DL system was significantly higher compared to those of the two junior radiologists, but not significantly different compared to seniors [DL system, 0.697; junior, 0.612 and 0.620 (P=0.021, 0.019); senior in consensus, 0.748 (P=0.071)]. Conclusions: The CNN-based DL system could assist junior radiologists in improving mass detection and is not affected by breast density. This DL system may have clinical utility in women with dense breasts, including reducing the impact caused by inexperienced radiologists and the potential for missed diagnoses.