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ABSTRACT: Over 1 year, two KPC-producing and two non–KPC-producing Klebsiella pneumoniae strains were isolated from a patient. Genome and DNA hybridization analyses revealed the first three strains as a clonal lineage, with carbapenem resistance changes due to a Tn2-like transposon on an IncR/IncFII plasmid. The fourth strain, carrying three plasmids, caused a lethal infection and represented a different lineage. All strains belonged to the ST11-SL47-OL101 type. This study highlights the Tn2-like transposon's role in carbapenemase gene spread and the importance of distinguishing between bacterial colonization and infection.

Abstract Purpose To explore the impact of different intraoperative intraocular pressure (IOP) settings on the safety and prognosis in phacoemulsification. Methods Age related cataract patients who met the inclusion criteria and underwent phacoemulsification by using active sentry handpiece and active fluidics system. According to different intraoperative IOP settings during surgery, they were randomly divided into two groups: the 20mmHg group and the 60mmHg group. The best corrected visual acuity (BCVA), cumulative dissipated energy (CDE), total U/S time, active surge mitigation (ASM), estimated fluid usage (EFU) as well as the changes in corneal thickness (CT), corneal epithelial layer thickness (CELT) and endothelial cell density (ECD) were collected. The post-operative follow-up was only 1 day. Results A total of 110 cases (110 eyes) were included in the study. There were 55 eyes in each group. There was no statistically significant difference in postoperative BCVA (p = 0.839). The CDE, total U/S time and EFU during surgery were (5.22 ± 3.31), (30.60 ± 15.06), (45.07 ± 12.68) and (4.70 ± 2.83), (27.39 ± 13.75), (42.38 ± 11.93) in the 20mmHg group and 60mmHg group (p = 0.381, 0.246, 0.254). The ASM during surgery in the 20mmHg group and 60mmHg group were (0.95 ± 2.77) and (7.24 ± 6.34), respectively. The 20mmHg group showed a significant decrease in ASM (p

Abstract Background Mesenchymal stem cells (MSCs) are one of the most widely studied adult stem cells, while MSC replicative senescence occurs with serial expansion in vitro. We determined whether miR-34a can regulate MSC senescence by directly targeting glycolytic key enzymes to influence glycolysis. Methods Detected the effects of miR-34a on MSC senescence and glycolytic metabolism through gene manipulation. Bioinformatics prediction and luciferase reporter assay were applied to confirm that HK1 is a direct target of miR-34a. The underlying regulatory mechanism of miR-34a targeting HK1 in MSC senescence was further explored by a cellular function recovery experiment. Results In the current study, we revealed that miR-34a over-expression exacerbated senescence-associated characteristics and impaired glycolytic metabolism. Then we identified hexokinase1 (HK1) as a direct target gene of miR-34a. And HK1 replenishment reversed MSC senescence and reinforced glycolysis. In addition, miR-34a-mediated MSC senescence and lower glycolytic levels were evidently rescued following the co-treatment with HK1 over-expression. Conclusion The miR-34a-HK1 signal axis can alleviate MSC senescence via enhancing glycolytic metabolism, which possibly provides a novel mechanism for MSC senescence and opens up new possibilities for delaying and suppressing the occurrence and development of aging and age-related diseases.

Abstract Background Bow Hunter’s syndrome (BHS), also known as rotational vertebral artery occlusion (RVAO), is a rare condition characterized by dynamic vertebrobasilar insufficiency due to position-dependent occlusion of the vertebral artery (VA). In the existing literature, most cases of BHS are attributed to osteophytic compression originating from the occipital condyle or within the transverse foramen, often accompanied by anatomical abnormalities of the VA. However, cases presenting solely with VA anomalies in the absence of any cervical vertebral structural abnormality are rare. This case report presents a unique instance of BHS in a 56-year-old male, attributed to the anomalous origin of the right VA and the absence of the left VA, without cervical structural abnormalities. Case presentation The patient exhibited symptoms like episodic dizziness and vertigo, which were exacerbated by rightward head rotation and alleviated upon returning to a neutral position. Diagnostic evaluation, including digital subtraction angiography, revealed that the right VA originated from the right common carotid artery and compression-induced stenosis of the right VA during head rotation. Conservative management, including avoidance of certain head movements and anti-arteriosclerosis medication, led to symptom resolution over a two-year follow-up period. Conclusions This report contributes to the understanding of BHS by highlighting a rare vascular anomaly presentation and incorporates a review of 14 similar case reports in the literature describing that an anatomical abnormality of the VA is mainly responsible for the pathology of BHS in the absence of cervical vertebral anomalies, thus emphasizing the need for careful diagnostic and management strategies.

Abstract Background The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. Methods Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. Results (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P

Abstract To use Optical Coherence Tomography (OCT) to measure scleral thickness (ST) and subfoveal choroid thickness (SFCT) in patients with Branch Retinal Vein Occlusion (BRVO) and to conduct a correlation analysis. A cross-sectional study was conducted. From May 2022 to December 2022, a total of 34 cases (68 eyes) of untreated unilateral Branch Retinal Vein Occlusion (BRVO) patients were recruited at the Affiliated Eye Hospital of Nanchang University. Among these cases, 31 were temporal branch vein occlusions, 2 were nasal branch occlusions, and 1 was a superior branch occlusion. Additionally, 39 cases (39 eyes) of gender- and age-matched control eyes were included in the study. Anterior Segment Optical Coherence Tomography (AS-OCT) was used to measure ST at 6 mm superior, inferior, nasal, and temporal to the limbus, while Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) was used to measure SFCT. The differences in ST and SFCT between the affected eye, contralateral eye, and control eye of BRVO patients were compared and analyzed for correlation. The axial lengths of the BRVO-affected eye, contralateral eye, and control group were (22.92 ± 0.30) mm, (22.89 ± 0.32) mm and (22.90 ± 0.28) mm respectively, with no significant difference in axial length between the affected eye and contralateral eye (P > 0.05). The SFCT and ST measurements in different areas showed significant differences between the BRVO-affected eye, contralateral eye in BRVO patients (P 0.05). However, significant differences were observed in SFCT and temporal, nasal, superior, and inferior ST between the two groups (P 0.05). In BRVO patients, both SFCT/CRT and ST increase, and there is a significant correlation between SFCT/CRT and the ST at the site of vascular occlusion.

Abstract Purpose Previous studies have reported the potential impact of immune cells on kidney stone disease (KSD), but definitive causal relationships have yet to be established. The purpose of this paper is to elucidate the potential causal association between immune cells and KSD by Mendelian randomization (MR) analysis. Methods In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between immune cell traits and kidney stone disease. We included a total of four immune traits (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)), which are publicly available data. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Cochran’s Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results. Results After FDR correction, the CD8 on HLA DR + CD8br (OR = 0.95, 95% CI = 0.93–0.98, p-value = 7.20 × 10− 4, q-value = 0.088) was determined to be distinctly associated with KSD, and we also found other 25 suggestive associations between immune cells and KSD, of which 13 associations were suggested as protective factors and 12 associations were suggested as risk factors. There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our Cochrane Q-test, MR Egger’s intercept test, and MR-PRESSO, which were all > 0.05. Conclusions Our study has explored the potential causal connection between immune cells and KSD by Mendelian randomization analysis, thus providing some insights for future clinical studies.

Abstract Background To compare the diagnostic performance of the Node-RADS scoring system and lymph node (LN) size in preoperative LN assessment for rectal cancer (RC), and to investigate whether the selection of size as the primary criterion whereas morphology as the secondary criterion for LNs can be considered the preferred method for clinical assessment. Methods Preoperative CT data of 146 RC patients treated with radical resection surgery were retrospectively analyzed. The Node-RADS score and short-axis diameter of size-prioritized LNs and the morphology-prioritized LNs were obtained. The correlations of Node-RADS score to the pN stage, LNM number and lymph node ratio (LNR) were investigated. The performances on assessing pathological lymph node metastasis were compared between Node-RADS score and short-axis diameter. A nomogram combined the Node-RADS score and clinical features was also evaluated. Results Node-RADS score showed significant correlation with pN stage, LNM number and LNR (Node-RADS of size-prioritized LN: r = 0.600, 0.592, and 0.606; Node-RADS of morphology-prioritized LN: r = 0.547, 0.538, and 0.527; Node-RADSmax: r = 0.612, 0.604, and 0.610; all p

In order to explore the quality characteristics of fermented kiwifruit black tea wine, kiwifruit and black tea were fermented, and the flavor and quality of fermented kiwifruit black tea wine were comprehensively analyzed by using high performance liquid chromatography, headspace solid-phase microextraction-gas chromatography-mass spectrometry and electronic nose technology, combined with sensory evaluation methods, through organic acid content, monomeric phenol content, amino acid content, volatile substances and sensory characteristics. The results showed that the types and contents of monomeric phenols and volatile substances in kiwifruit tea juice were significantly increased by fermentation (P

Abstract Non-self recognition is a fundamental aspect of life, serving as a crucial mechanism for mitigating proliferation of molecular parasites within fungal populations. However, studies investigating the potential interference of plants with fungal non-self recognition mechanisms are limited. Here, we demonstrate a pronounced increase in the efficiency of horizontal mycovirus transmission between vegetatively incompatible Sclerotinia sclerotiorum strains in planta as compared to in vitro. This increased efficiency is associated with elevated proline concentration in plants following S. sclerotiorum infection. This surge in proline levels attenuates the non-self recognition reaction among fungi by inhibition of cell death, thereby facilitating mycovirus transmission. Furthermore, our field experiments reveal that the combined deployment of hypovirulent S. sclerotiorum strains harboring hypovirulence-associated mycoviruses (HAVs) together with exogenous proline confers substantial protection to oilseed rape plants against virulent S. sclerotiorum. This unprecedented discovery illuminates a novel pathway by which plants can counteract S. sclerotiorum infection, leveraging the weakening of fungal non-self recognition and promotion of HAVs spread. These promising insights provide an avenue to explore for developing innovative biological control strategies aimed at mitigating fungal diseases in plants by enhancing the efficacy of horizontal HAV transmission.

Abstract In recent years, contrastive language‐image pre‐training (CLIP) has gained popularity for processing 2D data. However, the application of cross‐modal transferable learning to 3D data remains a relatively unexplored area. In addition, high‐quality, labelled point cloud data for Mechanical, Electrical, and Plumbing (MEP) scenarios are in short supply. To address this issue, the authors introduce a novel object detection system that employs 3D point clouds and 2D camera images, as well as text descriptions as input, using image‐text matching knowledge to guide dense detection models for 3D point clouds in MEP environments. Specifically, the authors put forth the proposition of a language‐guided point cloud modelling (PCM) module, which leverages the shared image weights inherent in the CLIP backbone. This is done with the aim of generating pertinent category information for the target, thereby augmenting the efficacy of 3D point cloud target detection. After sufficient experiments, the proposed point cloud detection system with the PCM module is proven to have a comparable performance with current state‐of‐the‐art networks. The approach has 5.64% and 2.9% improvement in KITTI and SUN‐RGBD, respectively. In addition, the same good detection results are obtained in their proposed MEP scene dataset.

Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate. However, most new chemical entities exhibit poor water solubility, and hence are exempt from such benefits. Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility, like other supersaturating systems, the problem of drug recrystallization has yet to be resolved, particularly within the dosage form. Here, we explored the potential of an emerging, non-leachable terpolymer nanoparticle (TPN) pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion (CRASD) beads comprising a poorly soluble drug (celecoxib) reservoir and insoluble polymer (ethylcellulose) membrane. Compared to conventional pore former, polyvinylpyrrolidone (PVP), TPN-containing membranes exhibited superior structural integrity, less crystal formation at the CRASD bead surface, and greater extent of celecoxib release. All-atom molecular dynamics analyses revealed that in the presence of TPN, intra-molecular bonding, crystal formation tendency, diffusion coefficient, and molecular flexibility of celecoxib were reduced, while intermolecular H-bonding was increased as compared to PVP. This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.

Numerous studies have shown that intestinal and urinary tract flora are closely related to the formation of kidney stones. The removal of probiotics represented by lactic acid bacteria and the colonization of pathogenic bacteria can directly or indirectly promote the occurrence of kidney stones. However, currently existing natural probiotics have limitations. Synthetic biology is an emerging discipline in which cells or living organisms are genetically designed and modified to have biological functions that meet human needs, or even create new biological systems, and has now become a research hotspot in various fields. Using synthetic biology approaches of microbial engineering and biological redesign to enable probiotic bacteria to acquire new phenotypes or heterologous protein expression capabilities is an important part of synthetic biology research. Synthetic biology modification of microorganisms in the gut and urinary tract can effectively inhibit the development of kidney stones by a range of means, including direct degradation of metabolites that promote stone production or indirect regulation of flora homeostasis. This article reviews the research status of engineered microorganisms in the prevention and treatment of kidney stones, to provide a new and effective idea for the prevention and treatment of kidney stones.

"Objective To explore the analgesic effects of brachial plexus block (BPB) guided by ultrasound versus localized by nerve stimulator in elderly patients who underwent humeral surgery. Methods Ninety nine elderly patients scheduled for open reduction and internal fixation of humeral fractures in Tongling Municipal Hospital from May 2020 to May 2023 were selected ,and randomly divided into ultrasound group (55 cases) and stimulator group (54 cases) based on a random number table method. The ultrasound-guided BPB was performed in ultrasound group, and the nerve stimulator localization for BPB was performed in stimulator group. The blocking effect, diaphragmatic function, hemodynamics indexes, stress indexes and perioperative adverse anesthesia reactions were compared between the two groups. Results The onset time［(4.82±1.44)min vs(6.95±1.87)min， t=6.675］ and improvement time ［(17.62±2.57)min vs(20.54±3.79)min， t=4.689］, and dosage of 0.75% bupivacaine hydrochloride ［(21.33±2.05)mL vs(25.54±2.52)mL， t=9.592］ in ultrasound group were lower than those in stimulator group (P＜0.01). After injecting drugs for 30min, the diaphragm mobility at calm breathing position ［(1.52±0.23)cm vs(1.24±0.22)cm］and at 〖JP2〗maximum breathing position ［(4.01±0.44)cm vs(3.19±0.49)cm］in ultrasound group were higher than those in stimulator group(P＜0.01). From entering the operating room to the end of surgery, heart rate (HR) and mean arterial pressure (MAP) of the two groups decreased first and then increased (P＜0.01), and the HR and MAP of ultrasound group were significantly higher than those of stimulator group from 10 min before the start of surgery to the end of the surgery (P＜0.05). Before surgery, on the day and 2 days after surgery, levels of serum epinephrine, norepinephrine and cortisol in the two groups showed a trend of first increasing and then decreasing (P＜0.01), but no significant difference was found between the two groups at each time point (P＞0.05). There was no significant difference in the incidence of perioperative adverse anesthesia reactions (agitation, nausea and vomiting, lethargy) between the two groups (P＞0.05). Conclusion Ultrasound-guided BPB has a fast block onset time, few effects on diaphragmatic function, stable hemodynamics and little stress response in elderly patients undergoing humeral surgery."

ABSTRACTUnderstanding the composition and community of airborne mycobiota associated with fungal diseases was critical for mushroom production and disease control. In this study, we first investigated airborne fungi concentrations in different function areas of a Chinese shiitake factory. Then, high-throughput sequencing was employed to characterise the airborne fungal compositions and communities of this factory during high and low incidence seasons of shiitake artificial log rot disease (SLRD). The lowest concentration of culturable airborne fungi was observed in spawn-running greenhouse (250–450 CFU/m3), while the airborne fungi concentrations in cultivation greenhouses were up to 7,000–8,500 CFU/m3. The airborne fungal communities across distinct function areas showed convergence. The four major mushroom contaminants, Trichoderma, Penicillium, Cladosporium, and Aspergillus were the stable core fungi. Seasonal shifts in compositions, abundances, and communities of airborne fungi were systematically analysed and found to be associated with SLRD. Compared with the SLRD low incidence season, the airborne fungal communities were rich but uneven in the SLRD high incidence season, in which Trichoderma was dominant. Further analysis indicated that the favourable temperature and humidity caused the proliferation of Trichoderma and then affected the fungal communities, which presented an SLRD-seasonal variation. SLRD incidence could be significantly reduced by reasonably increasing the ambient temperature. For the first time, we comprehensively characterised the dynamics of airborne fungal communities across the SLRD occurrence in the shiitake factory. Findings here also provided valuable information for fungal exposures in the mushroom industry.

Increasing evidence indicates that the remodeling of immune microenvironment heterogeneity influences pancreatic cancer development, as well as sensitivity to chemotherapy and immunotherapy. However, a gap remains in the exploration of the immunosenescence microenvironment in pancreatic cancer. In this study, we identified two immunosenescence-associated isoforms (IMSP1 and IMSP2), with consequential differences in prognosis and immune cell infiltration. We constructed the MLIRS score, a hazard score system with robust prognostic performance (area under the curve, AUC = 0.91), based on multiple machine learning algorithms (101 cross-validation methods). Patients in the high MLIRS score group had worse prognosis (P

Summary: Airway epithelial cells represent the first line of defense against respiratory pathogens. Flagellin drives the motility of many mucosal pathogens and has been suggested as an immune enhancing adjunctive therapeutic in infections of the airways. This study leveraged single-cell RNA sequencing to determine cell-specific effects of flagellin in primary human bronchial epithelial cells growing in air-liquid interface. Seven cell clusters were identified, including ciliated cells, ionocytes, and several states of basal and secretory cells, of which only inflammatory basal cells and inflammatory secretory cells demonstrated a proportional increase in response to flagellin. Inflammatory secretory cells showed evidence of metabolic reprogramming toward aerobic glycolysis, while in inflammatory basal cells transcriptome profiles indicated enhanced oxidative phosphorylation. Inhibition of mTOR prevented the shift to glycolysis and reduced inflammatory gene transcription specifically in inflammatory secretory cells. These data demonstrate the functional heterogeneity of the human airway epithelium upon exposure to flagellin.

Aims: To investigate the molecular mechanism of osteoclast-derived exosomes in osteoporosis. Main methods: RANKL induced osteoclast model was screened for significantly differentially expressed lncRNAs and mRNAs by whole RNA sequencing. Exosomes were characterized using electron microscopy, western blotting and nanosight. Overexpression or knockdown of AW011738 was performed to explore its function. The degree of osteoporosis in an osteoporosis model was assessed by mirco-CT. The osteoclast model, osteoblast differentiation ability and the molecular mechanism of lncRNA AW011738/miR-24-2-5p/TREM1 axis in osteoporosis were assessed by dual luciferase reporter gene assay, Western blotting (WB), immunofluorescence and ALP staining. Bioinformatics was used to predict interactions of key osteoporosis-related genes with miRNAs, transcription factors, and potential drugs after upregulation of AW011738. To predict the protein-protein interaction (PPI) network associated with key genes, GO and KEGG analyses were performed on the key genes. The ssGSVA was used to predict changes in the immune microenvironment. Key findings: Osteoclast-derived exosomes containing lncRNA AW011738 decreased the osteogenesis-related markers and accelerated bone loss in OVX mice. Osteoclast (si-AW011738)-derived exosomes showed a significant increase in biomarkers of osteoblast differentiation in vitro compared to the si-NC group. As analyzed by mirco-CT, tail vein injected si-AW011738 OVX mice were less osteoporotic than the control group. AW011738 inhibited osteoblast differentiation by regulating TREM1 expression through microRNA. Meanwhile, overexpression of miR-24-2-5p inhibited TREM1 expression to promote osteoblast differentiation. Significance: Osteoclast-derived exosomes containing lncRNA AW011738 inhibit osteogenesis in MC3T3-E1 cells through the lncRNA AW011738/miR-24-2-5p/TREM1 axis and exacerbate osteoporosis in OVX mice.

Abstract Toxoplasma gondii (T. gondii)‐associated polymorphic effector proteins are crucial in parasite development and regulating host anti‐T. gondii immune responses. However, the mechanism remains obscure. Here, it is shown that Toxoplasma effector dense granules 4 (GRA4) restricts host IFN‐I activation. Infection with Δgra4 mutant T. gondii strain induces stronger IFN‐I responses and poses a severe threat to host health. Mechanistically, GRA4 binds to phosphorylated TBK1 to promote TRIM27‐catalyzed K48‐ubiquitination at Lys251/Lys372 residues, which enhances its recognition by autophagy receptor p62, ultimately leading to TBK1 autophagic degradation. Furthermore, an avirulent Δgra4 strain (ME49Δompdc/gra4) is constructed for tumor immunotherapy due to its ability to enhance IFN‐I production. Earlier vaccination with ME49Δompdc/gra4 confers complete host resistance to the tumor compared with the classical ME49Δompdc treatment. Notably, ME49Δompdc/gra4 vaccination induces a specific CD64+MAR‐1+CD11b+ dendritic cell subset, thereby enhancing T cell anti‐tumor responses. Overall, these findings identify the negative role of T. gondii GRA4 in modulating host IFN‐I signaling and suggest that GRA4 can be a potential target for the development of T. gondii vaccines and tumor immunotherapy.

Summary: The Ralstonia solanacearum species complex causes bacterial wilt in a variety of crops. Tomato cultivar Hawaii 7996 is a widely used resistance resource; however, the resistance is evaded by virulent strains, with the underlying mechanisms still unknown. Here, we report that the phylotype Ⅱ strain ES5-1 can overcome Hawaii 7996 resistance. RipV2, a type Ⅲ effector specific to phylotype Ⅱ strains, is vital in overcoming tomato resistance. RipV2, which encodes an E3 ubiquitin ligase, suppresses immune responses and Toll/interleukin-1 receptor/resistance nucleotide-binding/leucine-rich repeat (NLR) (TNL)-mediated cell death. Tomato helper NLR N requirement gene 1 (NRG1), enhanced disease susceptibility 1 (EDS1), and senescence-associated gene 101b (SAG101b) are identified as RipV2 target proteins. RipV2 is essential for ES5-1 virulence in Hawaii 7996 but not in SlNRG1-silenced tomato, demonstrating SlNRG1 to be an RipV2 virulence target. Our results dissect the mechanisms of RipV2 in disrupting immunity and highlight the importance of converged immune components in conferring bacterial wilt resistance.

Mesenchymal stem/stromal cells (MSCs) have the capacity to migrate to tumor sites in vivo and transmit paracrine signals by secreting extracellular vesicles (EVs) to regulate tumor biological behaviors. MSC-derived EVs (MSC-EVs) have similar tumor tropism and pro- or anti-tumorigenesis as their parental cells and exhibit superior properties in drug delivery. MSC-EVs can transfer microRNAs (miRNAs) to tumor cells, thereby manipulating multiple key cancer-related pathways, and further playing a vital role in the tumor growth, metastasis, drug resistance and other aspects. In addition, tumor cells can also influence the behaviors of MSCs in the tumor microenvironment (TME), orchestrating this regulatory process via miRNAs in EVs (EV-miRNAs). Clarifying the specific mechanism by which MSC-derived EV-miRNAs regulate tumor progression, as well as investigating the roles of EV-miRNAs in the TME will contribute to their applications in tumor pharmacotherapy. This article mainly reviews the multifaceted roles and mechanism of miRNAs in MSC-EVs affecting tumor progression, the crosstalk between MSCs and tumor cells caused by EV-miRNAs in the TME. Eventually, the clinical applications of miRNAs in MSC-EVs in tumor therapeutics are illustrated.

Background: Limited studies have investigated the predictive value of multiomics signatures (radiomics, deep learning features, pathological features and DLG3) in breast cancer patients who underwent neoadjuvant chemotherapy (NAC). However, no study has explored the relationships among radiomic, pathomic signatures and chemosensitivity. This study aimed to predict pathological complete response (pCR) using multiomics signatures, and to evaluate the predictive utility of radiomic and pathomic signatures for guiding chemotherapy selection. Methods: The oncogenic function of DLG3 was explored in breast cancer cells via DLG3 knockdown. Immunohistochemistry (IHC) was used to evaluate the relationship between DLG3 expression and docetaxel/epirubin sensitivity. Machine learning (ML) and deep learning (DL) algorithms were used to develop multiomics signatures. Survival analysis was conducted by K-M curves and log-rank. Multivariate logistic regression analysis was used to develop nomograms. Results: A total of 311 patients with malignant breast tumours who underwent NAC were retrospectively included in this multicentre study. Multiomics (DLG3, RADL and PATHO) signatures could accurately predict pCR (AUC: training: 0.900; testing: 0.814; external validation: 0.792). Its performance is also superior to that of clinical TNM staging and the single RADL signature in different cohorts. Patients in the low DLG3 group more easily achieved pCR, and those in the high RADL Signature_pCR and PATHO_Signature_pCR (OR = 7.93, 95 % CI: 3.49–18, P < 0.001) groups more easily achieved pCR. In the TEC regimen NAC group, patients who achieved pCR had a lower DLG3 score (4.00 ± 2.33 vs. 6.43 ± 3.01, P < 0.05). Patients in the low RADL_Signature_DLG3 and PATHO_Signature_DLG3 groups had lower DLG3 IHC scores (P < 0.05). Patients in the high RADL signature, PATHO signature and DLG3 signature groups had worse DFS and OS. Conclusions: Multiomics signatures (RADL, PATHO and DLG3) demonstrated great potential in predicting the pCR of breast cancer patients who underwent NAC. The RADL and PATHO signatures are associated with DLG3 status and could help doctors or patients choose proper neoadjuvant chemotherapy regimens (TEC regimens). This simple, structured, convenient and inexpensive multiomics model could help clinicians and patients make treatment decisions.

PurposeSmall dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design.MethodsWe identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis.ResultsIn univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117–1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106–1.597, P = 0.002).ConclusionsFindings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C.

ObjectiveTo investigate the expression and clinical significance of GATA-3 and H3K27me3 in Tibetan patients with bladder urothelial carcinoma (BUC).MethodsBUC and normal bladder tissues were collected retrospectively from January 2016 to December 2021 in the People's Hospital of Tibet Autonomous Region. The expression of GATA-3 and H3K27me3 in both tissues was detected by immunohistochemical method, and the clinical and pathological characteristics were statistically analyzed.ResultsA total of 70 patients with BUC were selected, including 51 males and 19 females, with an average age of (60.5±12.0) years. At the same time, 20 normal bladder tissue samples were collected during the same period. All cases were Tibetan patients. Immunohistochemistry results showed that the high expression rate of GATA-3 in BUC and normal bladder tissue was 70.0%(49/70) and 100%(20/20), respectively. High expression of GATA-3 was associated with male, low pathological grade, and non-invasive tissue(all P < 0.05). The high expression rate of H3K27me3 in BUC and normal bladder tissue was 45.7%(32/70) and 20.0%(4/20), respectively. High expression of H3K27me3 was only associated with male (P=0.011).ConclusionsThe expression of GATA-3 was down regulated in Tibetan BUC patients, and significantly down regulated with the increase of tumor grade, suggesting that GATA-3 may be involved in the occurrence and development of BUC and related to its malignancy, providing reference for clinical diagnosis and treatment as well as judging disease prognosis. The expression of H3K27me3 in Tibetan BUC patients was higher than that in normal bladder tissue, suggesting that H3K27me3 may be a new immune marker for diagnosis of BUC.

Abstract Objectives Methicillin-resistant Staphylococcus aureus (MRSA) is a challenging global health threat, resulting in significant morbidity and mortality worldwide. This study aims to determine the molecular characteristics and antimicrobial susceptibility of 263 MRSA isolates in Zhejiang Province, east China. Methods From 2014 to 2019, a total of 263 MRSA isolates from bloodstream infections (BSIs) were collected from 6 hospitals in 4 cities in Zhejiang province, east China. Antimicrobial susceptibility tests were conducted according to the guidelines set forth by the Clinical and Laboratory Standards Institute (CLSI). To characterize and analyze these isolates, multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) typing and virulence genes gene profiles were performed. Results The most predominant clone was ST5-SCCmec II-t311, which accounted for 41.8% (110/263), followed by ST59 (44/263, 16.7%). Compared with non-ST5-II-t311 isolates, ST5-II-t311 isolates were more resistant to erythromycin, tetracycline, levofloxacin, moxifloxacin, and ciprofloxacin, but more susceptible to clindamycin. Moreover, the rates of multidrug resistance were higher in ST5-II-t311 isolates compared to the non-ST5-II-t311 isolates. In comparison to the non-ST5-II-t311 isolates, ST5-II-t311 isolates showed no significant difference in virulence genes detected. Conclusions MRSA ST5-II-t311 clone has become the most predominant clone in Zhejiang Province, east China and has higher rates of multidrug resistance than other isolates, that should be kept in mind when treating BSI. Moreover, MRSA ST59 clone shows an upward trend and has begun to spread into hospitals. Our findings highlight the importance of epidemiological studies of S. aureus carriage in the eastern region.

Three-dimensional (3D) printing is emerging as an innovative technology, which is widely used in cardiovascular disease at bench and bedside. During the last decade, with the development of 3D printing industry, many 3D printed models have been used in clinic, because it can provide the advantage of haptic feedback, direct manipulation, and enhanced doctors’ understanding of cardiovascular anatomy and underlying pathologies. In addition to the preparation of 3D printed models, 3D printing technology also shows great application potential in cardiovascular regenerative medicine because it has the advantages of integrating cells, cytokines and materials. Although cardiovascular regenerative medicine application still has a gap between bench and bedside, this gap is gradually narrowing with the development of new materials and new technology of 3D printing recently. In this review, we firstly analyze the characteristics and clinical needs of cardiovascular diseases, and introduce the concept and category of 3D printing technology. Secondly, we summarize the application of 3D printed models, stents, vascular graft, vascular network, and heart organs at bench and bedside. In the end, we discuss the challenges and future perspectives of 3D printing in cardiovascular diseases.

Abstract Background A novel approach known as intraosseous regional administration (IORA) has emerged as a technique for delivering prophylactic antibiotics, and it results in higher tissue concentrations around the knee. It is hypothesized that IORA of cefazolin for antibiotic prophylaxis during total knee arthroplasty will result in sustained effective levels for a longer duration. The aim of the current study was to investigate temporal changes in peri-knee cefazolin blood concentrations after IORA of cefazolin. Methods Twelve rabbits were randomly divided into two groups, with six rabbits in each group. In control group a single intravenous bolus injection of cefazolin (10 mL, 100 mg) was administered into the marginal ear vein. In experimental groupexperimental group the same dose of cefazolin was injected into the left tibial marrow cavity after tourniquet inflation at the base of the left thigh. Blood samples were collected periodically at different timepoints, and cefazolin concentrations were determined. Results The intraosseous treatment resulted in significant differences in plasma cefazolin concentrations at all timepoints. Experimental group exhibited higher plasma cefazolin concentrations than control group. Conclusions Cefazolin in intraosseous regional prophylaxis exhibits effectiveness in intraoperative antibiotic prophylaxis by maintaining concentrations above the minimum inhibitory concentration for extended durations, rather than relying solely on high concentrations.

Abstract Deoxynivalenol (DON) is the most frequently detected mycotoxin in cereal grains and processed food or feed. Two transcription factors, Tri6 and Tri10, are essential for DON biosynthesis in Fusarium graminearum. In this study we conduct stranded RNA-seq analysis with tri6 and tri10 mutants and show that Tri10 acts as a master regulator controlling the expression of sense and antisense transcripts of TRI6 and over 450 genes with diverse functions. TRI6 is more specific for regulating TRI genes although it negatively regulates TRI10. Two other TRI genes, including TRI5 that encodes a key enzyme for DON biosynthesis, also have antisense transcripts. Both Tri6 and Tri10 are essential for TRI5 expression and for suppression of antisense-TRI5. Furthermore, we identify a long non-coding RNA (named RNA5P) that is transcribed from the TRI5 promoter region and is also regulated by Tri6 and Tri10. Deletion of RNA5P by replacing the promoter region of TRI5 with that of TRI12 increases TRI5 expression and DON biosynthesis, indicating that RNA5P suppresses TRI5 expression. However, ectopic constitutive overexpression of RNA5P has no effect on DON biosynthesis and TRI5 expression. Nevertheless, elevated expression of RNA5P in situ reduces TRI5 expression and DON production. Our results indicate that TRI10 and TRI6 regulate each other’s expression, and both are important for suppressing the expression of RNA5P, a long non-coding RNA with cis-acting inhibitory effects on TRI5 expression and DON biosynthesis in F. graminearum.

Abstract Objective The objective of this study was to investigate the correlation between various factors and the clinical outcomes of Intrauterine Insemination (IUI) in both young and aged patients, aiming to provide a theoretical basis for clinical consultations. Methods This retrospective analysis examined a total of 4,221 IUI cycles conducted at the Reproductive Center of Changzhou Maternal and Child Health Hospital between January 2016 and December 2020. The patients were categorized into two groups based on age: the elder group (≥ 35 years) and the young group (

Abstract Background An increasing body of observational studies have indicated an association between gut microbiota and endometriosis. However, the causal relationship between them is not yet clear. In this study, we employed Mendelian randomization method to investigate the causal relationship between 211 gut microbiota taxa and endometriosis. Methods Independent genetic loci significantly associated with the relative abundance of 211 gut microbiota taxa, based on predefined thresholds, were extracted as instrumental variables. The primary analytical approach employed was the IVW method. Effect estimates were assessed primarily using the odds ratio and 95% confidence intervals. Supplementary analyses were conducted using MR-Egger regression, the weighted median method, the simple mode and the weighted mode method to complement the IVW results. In addition, we conducted tests for heterogeneity, horizontal pleiotropy, sensitivity analysis, and MR Steiger to assess the robustness of the results and the strength of the causal relationships. Results Based on the IVW method, we found that the family Prevotellaceae, genus Anaerotruncus, genus Olsenella, genus Oscillospira, and order Bacillales were identified as risk factors for endometriosis, while class Melainabacteria and genus Eubacterium ruminantium group were protective factors. Additionally, no causal relationship was observed between endometriosis and gut microbiota. Heterogeneity tests, pleiotropy tests, and leave-one-out sensitivity analyses did not detect any significant heterogeneity or pleiotropic effects. Conclusions Our MR study has provided evidence supporting a potential causal relationship between gut microbiota and endometriosis, and it suggests the absence of bidirectional causal effects. These findings could potentially offer new insights for the development of novel strategies for the prevention and treatment of endometriosis.

Abstract Modern automotive propulsion technologies must achieve the highest CO2 reduction potential quickly to abide by the requirements of the Paris Climate Agreement. A collective utilization of renewable fuels, e‐fuels, hydrogen, and electrical energy will be able to meet different mobility and transport requirements in an optimal and CO2‐neutral approach. The well‐to‐wheel greenhouse gas emissions of a propulsion system are determined by two factors, that is, the energy efficiency of the system and the carbon intensity of the energy source. Regardless of the CO2 emission generated during the battery manufacturing and recycling process, the carbon intensity of the battery electric vehicles during operation is mainly decided by the carbon intensity of the electricity being consumed. The relatively low fleet ratios of battery electric and hydrogen‐powered vehicles and the massive remaining useful life of current internal combustion engine vehicle stock limit their impact on decarbonization in the near term. The expansion of charging infrastructure requires significant acceleration for the success of large‐scale and rapid electric vehicle adoption. For internal combustion engines, the focus is to further improve energy efficiency and the adoption of low‐to‐zero carbon renewable fuels. Hybrid and plug‐in hybrid vehicles are demonstrating the advantages of combining state‐of‐the‐art technologies to reduce both energy consumption and carbon emissions. In this review, the present status of propulsion systems is reviewed in detail, considering both the market penetration and well‐to‐wheel carbon emissions. The decarbonization potentials of various propulsion systems are then discussed.

[Objective] In water-rich rock stratum regions, preventing confined aquifer inrush accidents is a key focus and challenge in the design and construction of deep foundation pit projects. Accurately and effectively determining the critical thickness of foundation pit bottom plate is crucial in preventing confined aquifer inrush accidents. Therefore, it is necessary to conduct stability study on foundation pit bottom plate inrush damage problem in confined aquifer. [Method] Based on the nonlinear Mohr-Coulomb failure criterion and considering the influence of various strength parameters and the heterogeneity characteristics of soil layers, a mechanical analysis model for foundation pit bottom plate inrush damage is established. Using the limit equilibrium method, a safety factor calculation formula for bottom plate inrush stability considering the inherent strength of soil layers is proposed. The calculation method for inrush damage in the current technical specifications for foundation pit support is modified. Taking the foundation pit of a utility tunnel project in soft soil layers in Jinan as example, the effectiveness of the proposed modified calculation formula for pit bottom plate inrush stability is validated. Additionally, variations in the safety factor of bottom plate inrush stability under the influence of different soil strength parameters, impermeable layer thickness, and confined water pressure are analyzed. [Result & Conclusion] With the increase in soil cohesion, heterogeneity constant, density, and impermeable layer thickness, the safety factor of pit bottom plate inrush stability continuously increases. Conversely, as the soil nonlinear coefficient, confined water pressure, and foundation pit width increase, the safety factor of pit bottom plate inrush stability continuously decreases. The calculated values of the inrush safety factors considering the influence of soil inherent strength parameters, are generally greater than the values obtained using the current calculation method in the technical specifications for foundation support. The verification using the proposed modified inrush stability calculation formula is more economical.

Abstract With a detailed historical analysis of postwar Japanese female employment, this article presents three underlying policy perspectives that shape the fact that women have less chance for high-quality employment despite the rising labor force participation rate. The three assumptions of women's role in policy-making are as follows: (1) women as housewives—dependent on males, do not earn a living salary and are thus marginalized in the labor market; (2) women as individuals pursuing gender equality should be treated without discrimination in the workplace; and (3) women as key drivers for economic growth can contribute to the solution to labor shortages. The postwar history of Japanese female employment is full of interaction among these three policy perspectives. Generally, it passes through phases of the dominance of the housewife perspective, the reformation from the equality perspective and the counterattack from the housewife perspective, as well as the mainstreaming of the economic actor perspective.

In this work, an accurate temperature-dependent drain current $I_{\mathrm { D}}$ fluctuation model valid from 10 to 300 K was proposed for 18 nm ultra-thin body and buried oxide (UTBB) n-channel field effect transistors (n-FETs). The temperature dependence of $I_{\mathrm { D}}$ fluctuation was characterized and investigated from 300 K down to 10 K. In moderate inversion mode, $I_{\mathrm { D}}$ fluctuation is more severe at sub-100 K while in the strong inversion mode, it still can be overshadowed by the charge screening effect. Cryogenic virtual source (CVS) device model was used to extract and analyze the carrier density and mobility which are used in the current fluctuation model. The current fluctuation model was experimentally verified under different inversion conditions, showing it can be used to analyze and optimize the flicker noise in the low temperature (LT) circuit applications.

FESS (flywheel energy storage system) motor is used in important load fields for instance rail transit; meanwhile the power flow is formed through the connection between FESS (flywheel energy storage system) and power grid system, which can critically improve the power flow fluctuation caused by new energy grid integration regarding wind and photovoltaic generation concerning that the motor speed in FESS is related to its energy storage capacity. Aiming at the limitation of current low motor speed in the FESS, this article puts forward a high-speed grid-connected FESS, and designs a model via the proposed dual-PWM two-stage control form, which is named as double closed-loop control. In this article, the FESS, as well as the power grid system, is analyzed and simulated in three stages: charging, pre-grid connection and grid connection. In this way, the flywheel motor speed and DC bus voltage signal are sampled to design the flywheel motor side with the proposed method. Then the grid-connected double closed-loop control method is designed for the sampling observation points, which realizes the efficient design on the control strategy of proposed high-speed grid-connected FESS and the verification of voltage and current parameters. The simulation experiments show that the operation process of the grid-connected FESS motor obtains its rapid speed response characteristic, which can meet the proposed design requirements during the charging and discharging process.

The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury. Ruxolitinib, a JAK-STAT inhibitor, exhibits effectiveness in autoimmune diseases, arthritis, and managing inflammatory cytokine storms. Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma, the exact mechanism by which it enhances functional recovery after spinal cord injury, particularly its effect on astrocytes, remains unclear. To address this gap, we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury. Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury, restored EAAT2 expression, reduced glutamate levels, and alleviated excitatory toxicity. Furthermore, ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β, interleukin-6, and tumor necrosis factor-α. Additionally, in glutamate-induced excitotoxicity astrocytes, ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3, thereby reducing glutamate-induced neurotoxicity, calcium influx, oxidative stress, and cell apoptosis, and increasing the complexity of dendritic branching. Collectively, these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes, reduces neurotoxicity, and effectively alleviates inflammatory and immune responses after spinal cord injury, thereby promoting functional recovery after spinal cord injury.

Radar is a valuable tool for noncontact vital-sign detection. Interference from respiratory harmonics presents a major challenge in radar cardiogram (RCG) extraction—mainly when the frequency of respiratory harmonics is close to or equal to that of the cardiac sub-signals. To address this problem, a respiratory harmonic suppression method employing correlation analysis and an optimized feedback notch filter is proposed, which is based on 7.29 GHz center-frequency impulse-radio ultra-wideband radar. A genetic optimization algorithm is employed to optimize the parameters of the notch filter. Performance comparison analysis is conducted on the conventional notch filter and the feedback notch filter. Contact (ECG) and non-contact (RCG) data from 10 subjects were analyzed. The results verified that the performance of the optimized feedback notch filter is much better than that of the conventional notch filter in overshoot, bandwidth, and notch depth, and the proposed method can effectively locate, identify, and suppress respiratory harmonics from the RCG band while preserving heartbeat components. Consequently, this approach markedly enhances the precision of RCG extraction. The technique shows considerable promise for deployment in diverse practical settings, including non-contact auxiliary monitoring systems in both intelligent medical environments and home healthcare.

Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disease that affects multiple organs and systems throughout the body. TSC-associated kidney disease is the leading cause of death in adult TSC patients. This article retrospectively analyzed the characteristics of one TSC-related renal giant angiomyolipoma(RAML)treated with surgery. The patient, 25 years old, was diagnosed with tuberous sclerosis complex in 2000 due to multiple maculopapular rashes on both cheeks. At a regular follow-up in July 2019, imaging examinations revealed a tumor in the left lower quadrant with a maximum cross-sectional area of 16 cm×7 cm. Genetic testing showed a loss of heterozygosity in the EX18_ 41 of TSC2. After the diagnosis was confirmed, open left partial nephrectomy was performed, during which multiple tumors were found on the kidney surface and the largest one was located on the ventral side with a diameter of approximately 20 cm. After the renal artery was occluded, kidney tumors were completely enucleate. Postoperative pathological confirmed the diagnosis of angiomyolipoma. This case provides a reference for the treatment of TSC-related renal giant hamartoma.

Correctly performed Cardiopulmonary Resuscitation (CPR) is a critical element in preventing deaths caused by cardiac arrest (CA). To improve the outcomes and quality of CPR, stand-alone devices that monitor the performance and provide feedback have been developed. However, these devices have multiple limitations due to their rigidity and stiffness. Furthermore, most of the devices do not account for complete chest recoil as a metric of quality CPR, reducing the quality of compressions. To overcome these limitations, this study proposes smart gloves equipped with e-textiles-based pressure sensors and inertial measurement units (IMUs) to monitor the quality adult CPR in real-time. The prototype development combined data-driven design and Research Through Design (RtD) methods, taking into account not only the accuracy but also the usability of the smart gloves. A preliminary study with nine participants performing CPR on a doll was conducted to evaluate the accuracy and wearability of the smart gloves. Study results show that the smart gloves accurately detect chest compression parameters, including compression depth, compression rate, chest recoil and interruption between compressions based on the intelligent fusion of pressure sensors and IMUs. In addition, the newly developed smart gloves are lightweight, hand adaptable, and easily replicable as an alternative for hard case devices. The design methods used in this study can be applied to design other accessible and comfortable wearable devices in healthcare settings.

Objective: This study was designed to evaluate the feasibility, efficacy, and safety of percutaneous ureteroscopy laser unroofing as an ambulatory surgery for symptomatic simple renal cysts under multilevel paravertebral nerve block anesthesia. Methods: From December 2015 to September 2017, 33 simple renal cyst patients who had surgical indications were enrolled. Under ultrasound guidance, the T10/T11, T11/T12, and T12/L1 paravertebral spaces were identified, and 7–10 mL 0.5% ropivacaine was injected at each segment. Then a puncture needle was placed inside the cyst cavity under ultrasonic monitoring. A guidewire was introduced followed by sequential dilation up to 28/30 Fr. The extra parenchymal portion of the cyst wall was dissociated and incised using a thulium laser, and a pathological examination was performed. Results: Sensory loss to pinprick from T8 to L1 and sensory loss to ice from T6 to L2 were observed in all patients. None of the patients complained of pain during surgery. No serious complications occurred perioperatively. After the surgery, all patients recovered their lower limb muscle strength quickly, got out of bed, resumed oral feeding, and left the hospital within 24 h of admission. The pathologic diagnosis of all cyst walls was a simple renal cyst. The mean follow-up was 35.8 months. At the end of follow-up, the cyst units were reduced in size by more than 50% compared to the preoperative size, and no patient experienced a recurrence. Conclusion: Multi-level paravertebral nerve block for percutaneous ureteroscopy laser unroofing as an ambulatory surgery mode is feasible, safe, and effective for the treatment of simple renal cysts in selected patients.

The Yunnan-Tibet railway is located in the southeastern edge of the Tibetan Plateau, where tectonic plates collide and the terrain rapidly changes. Along the line, active faults develops, earthquakes occur frequently, and the intensity of earthquakes is strong, moreover, geological disasters are frequent. Hence its planning, construction, and long-term operation face severe geological safety risks. More than 10 active fault zones have been developed along the Shangri La-Bomi section of the Yunnan-Tibet railway, including the Haba-Yulong Snow Mountain east foot fault zone, Zhongdian-Longpan fault zone, Deqin-Zhongdian-Daju fault zone, Weixi-Qiaohou fault zone, Jinsha river fault zone, Batang fault zone, Lancang river fault zone, Nujiang fault zone, Bianba-Luolong fault zone, and Jiali-Chayu fault zone. These active fault zones are highly affected by fault slip dislocations, creep deformation, and the risk of triggering strong earthquakes. There is an urgent need to determine the geometric distribution and activity of regional active fault zones. Based on previous research, remote sensing interpretation, and field investigations, this article summarizes and analyzes the geometric distribution, kinematic properties, slip rate and paleoearthquake sequence of more than 10 active fault zones along the route, providing basic information for the planning, construction and safe operation of major national projects such as the Yunnan-Tibet railway.

Objective To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) and radical surgery for non-metastatic pancreatic cancer (PC).Materials and methods We retrospectively analyzed 89 stage I/II/III PC patients who underwent HIFU (n = 43) or surgery (n = 46) at the Third Xiangya Hospital from January 2020 to December 2021. Pain relief, Karnofsky Performance Scale (KPS), overall survival (OS), treatment-related complications and risk factors for OS were assessed.Results There was no significant difference in the pain relief rate at 30 days post-treatment between the two groups. However, compared with the surgery group, the HIFU group showed significantly lower post-treatment VAS scores (p = 0.019). In the surgery group, the KPS at 30 days post-treatment was lower than pretreatment KPS (70 vs 80; p = 0.015). This relationship was reversed in the HIFU group (80 vs 70; p = 0.024). Median OS favored surgery over HIFU (23 vs 10 months; p

To investigate the synergistic effect of IAA and melatonin (MT) on three plants to alleviate the effects of salt damage on plants, we aim to determine the optimal concentrations of exogenous hormone treatments that improve salinity resistance for each species. In this experiment, three desert plants, Sarcozygium xanthoxylon, Nitraria tangutorum, and Ammopiptanthus mongolicus, which are common in Wuhai City, were used as plant materials. Two time periods (12 h,24 h) of exogenous hormone IAA (100 μmol/L) and exogenous melatonin concentration (0, 100, 200, 300 μmol/L) were used to treat the three desert plants in saline soil under different conditions of exogenous IAA and exogenous melatonin. The results indicate that under different concentrations of exogenous IAA and melatonin, the germination rate and vigor of the three desert plant species in saline-alkaline soil improved. However, as the concentration of melatonin increased, the germination rate and vigor of these desert plants were inhibited. Whereas, plant height, root length, leaf length, fresh weight, dry weight, and root vigor of the three desert plants were alleviated under different conditions of exogenous IAA and exogenous melatonin. under the action of two exogenous hormones, the low concentration of melatonin decreased their malondialdehyde content and increased their proline content. As melatonin levels increased, the activity of antioxidant enzymes also rose initially, followed by a subsequent decline. This study highlights the synergistic effects of two exogenous hormones on the critical role of cell osmomodulators and antioxidant enzyme activity in combating salinity damage in three desert plants.

Ethyl carbamate (EC), a carcinogen commonly found in Baijiu, requires an efficient detection method for quality control and monitoring. This study introduces a novel molecularly imprinted electrochemical sensor for sensitive and selective EC detection. We proposed a simple sol-gel method for the growth of perovskite-structured lanthanum manganate (LaMnO3) on graphene oxide (GO). A non-enzymatic electrochemical sensor was developed by coating a molecularly imprinted polymer synthesized via precipitation polymerization onto the surface of LaMnO3@GO. LaMnO3, with its superior three-dimensional nanocube structure, demonstrated excellent electrocatalytic activity, while the addition of GO provided a large specific surface area. The results indicate that the developed sensor exhibits exceptional recognition ability and electrochemical activity, which is attributed to the high affinity of LaMnO3@GO@MIP for EC. The sensor displays a broad linear range from 10 to 2000 μM, with a detection limit as low as 2.18 μM and long-term durability of 28 days. Notably, it demonstrates excellent selectivity, reproducibility, and stability even under different interference conditions. The sensor was successfully used to determine EC in real Baijiu samples. Overall, the sensor has broad application prospects for detecting trace contaminants in the field of food safety.

Radiotherapy (RT) is one of major therapeutic modalities in combating breast cancer. In RT, ionizing radiation is employed to induce DNA double-strand breaks (DSBs) as a primary mechanism that causes cancer cell death. However, the induced DNA damage can also trigger the activation of DNA repair mechanisms, reducing the efficacy of RT treatment. Given the pivotal role of RAD50 protein in the radiation-responsive DNA repair pathways involving DSBs, we developed a novel polymer-lipid based nanoparticle formulation containing RAD50-silencing RNA (RAD50-siRNA-NPs) and evaluated its effect on the RAD50 downregulation as well as cellular and tumoral responses to ionizing radiation using human triple-negative breast cancer as a model. The RAD50-siRNA-NPs successfully preserved the activity of the siRNA, facilitated its internalization by cancer cells via endocytosis, and enabled its lysosomal escape. The nanoparticles significantly reduced RAD50 expression, whereas RT alone strongly increased RAD50 levels at 24 h. Pretreatment with RAD50-siRNA-NPs sensitized the cancer cells to RT with ∼2-fold higher level of initial DNA DSBs as determined by a γH2AX biomarker and a 2.5-fold lower radiation dose to achieve 50 % colony reduction. Intratumoral administration of RAD50-siRNA-NPs led to a remarkable 53 % knockdown in RAD50. The pretreatment with RAD50-siRNA-NPs followed by RT resulted in approximately a 2-fold increase in DNA DSBs, a 4.5-fold increase in cancer cell apoptosis, and 2.5-fold increase in tumor growth inhibition compared to RT alone. The results of this work demonstrate that RAD50 silencing by RAD50-siRNA-NPs can disrupt RT-induced DNA damage repair mechanisms, thereby significantly enhancing the radiation sensitivity of TNBC MDA-MB-231 cells in vitro and in orthotopic tumors as measured by colony forming and tumor regrowth assays, respectively.

Lonicerae japonicae flos (LJF), Lonicerae japonicae caulis (LJC), Lonicerae folium (LF) and Lonicerae fructus (LFR) are derived from Lonicera japonica Thunb., which are formed due to different medicinal parts. The efficacy of the 4 medicinal materials has similarities and differences. However, little attention has been paid to illustrate the differences in efficacy from the perspective of phytochemistry. In this study, ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UPLC-Q-Exactive-Orbitrap-MS) was used to qualitatively analyze the ingredients in 4 herbs. A total of 86 compounds were plausibly or unambiguously identified, there were 54 common components among the 4 medicinal materials, and each kind of medicinal materials had its own unique components. On the basis of qualitative analysis, ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-QQQ-MS/MS) was used to quantitatively analyze 31 components contained in 4 medicinal materials, and principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and other multivariate statistical analysis were furtherly performed for comparing the component contents. The results showed that the samples from the same parts were clustered into one group, and the samples from different medicinal parts were significantly different. The analysis of variable importance projection (VIP) value of the OPLS-DA model showed that 10 components including chlorogenic acid, secologanic acid, isochlorogenic acid A, loganin, lonicerin, loganic acid, secoxyloganin, sweroside, luteolin and rhoifolin were the main difference components among the 4 medicinal materials. The study not only lays a solid foundation for the intrinsic quality control of 4 medicinal materials and the study of different effects of the 4 medicinal materials at the phytochemical level, but also provides a basis for more rational utilization of various parts of L. japonica and expansion of medicinal resources.

ABSTRACT Ascospores, forcibly released into the air from perithecia, are the primary inoculum for Fusarium head blight. In Fusarium graminearum, the biological functions of four RNA-dependent RNA polymerases (RdRPs) (Fgrdrp1–4) have been reported, but their regulatory mechanisms are poorly understood and the function of Fgrdrp5 is still unknown. In this study, we found that in addition to Fgrdrp1 and Fgrdrp2, Fgrdrp5 also plays an important role in ascospore discharge, and they all participate in the generation of turgor pressure in a polyol-dependent manner. Moreover, these three genes all affect the maturation of ascospores. Deep sequencing and co-analysis of small RNA and mRNA certified that Fgrdrp1, Fgrdrp2, and Fgrdrp5 partly share their functions in the biogenesis and accumulation of exonic small interference RNA (ex-siRNA), and these three RdRPs negatively regulate the expression levels of ex-siRNA corresponding genes, including certain genes associated with ascospore development or discharge. Furthermore, the differentially expressed genes of deletion mutants, those involved in lipid and sugar metabolism or transport as well as sexual development-related transcription factors, may also contribute to the defects in ascospore maturation or ascospore discharge. In conclusion, our study suggested that the components of the dicer-dependent ex-siRNA-mediated RNA interference pathway include at least Fgrdrp1, Fgrdrp2, and Fgrdrp5.IMPORTANCEWe found that in addition to Fgrdrp1 and Fgrdrp2, Fgrdrp5 also plays important roles in ascospore maturation and ascospore discharge of Fusarium graminearum. These three RNA-dependent RNA polymerases participate in the biogenesis and accumulation of exonic small interference RNA and then regulate ascospore discharge.

BackgroundThe metabolic score for insulin resistance (METS-IR) has emerged as a noninsulin-based index for the approximation of insulin resistance (IR), yet longitudinal evidence supporting the utility of METS-IR in the primary prevention of type 2 diabetes mellitus (T2DM) remains limited. ObjectiveWe aimed to investigate the longitudinal association between METS-IR, which combines fasting plasma glucose (FPG), lipid profiles, and anthropometrics that can be routinely obtained in resource-limited primary care settings, and the incidence of new-onset T2DM. MethodsWe conducted a closed-cohort analysis of a nationwide, prospective cohort of 7583 Chinese middle-aged and older adults who were free of T2DM at baseline, sampled from 28 out of 31 provinces in China. We examined the characteristics of participants stratified by elevated blood pressure (BP) at baseline and new-onset T2DM at follow-up. We performed Cox proportional hazard regression analysis to explore associations of baseline METS-IR with incident T2DM in participants overall and in participants stratified by baseline BP. We also applied net reclassification improvement and integrated discrimination improvement to examine the incremental value of METS-IR. ResultsDuring a mean follow-up period of 6.3 years, T2DM occurred in 527 participants, among which two-thirds (332/527, 62.9%; 95% CI 58.7%-67.1%) had baseline FPG

Abstract Background and Objective The neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) were significant and succinct indicators of systemic inflammation. We assessed the influence of stereotactic body radiotherapy (SBRT) on NLR and PLR in patients with locally advanced non‐small cell lung cancer (LA‐NSCLC). Methods We reviewed the medical data of patients with LA‐NSCLC who underwent SBRT between 1 January 2013 and 31 December 2018. NLR and PLR values recorded at pre‐ and post‐SBRT were examined. We assessed the correlation between pre/post‐SBRT NLR and PLR and survival outcomes. The decision tree evaluation was conducted using Chi‐square automatic detection. Results In total, 213 patients were included in the study with a median follow‐up duration of 40.00 (ranging from 5.28 to 100.70) months. Upon dichotomization by a median, we identified that post‐SBRT NLR > 5.5 and post‐SBRT PLR > 382.0 were negatively associated with shorter overall survival (OS). In the multivariate assessment, post‐SBRT PLR > 382.0 was the only factor. Based on post‐SBRT PLR, tumor locations, and tumor stage, we categorized patients into low, medium, or high‐risk groups. Conclusions Post‐SBRT PLR > 382.0 correlated with survival in patients undergoing SBRT. The decision tree model might play a role in future risk stratification to guide the clinical practice of individualized SBRT for LA‐NSCLC.