Giant strong coupling in a Q-BICs' tetramer metasurface.

Due to their ultrahigh Q-factor and small mode volume, bound states in the continuum (BICs) are intriguing for the fundamental study of the strong coupling regime. However, the strong coupling generated by BICs in one metasurface is not always strong enough, which highly limits its efficiency in applications. In this work, we realize a giant strong coupling of at most 60 meV in a quasi-BICs' (Q-BICs) tetramer metasurface composed of four Si cylinders with two different sets of diagonal lengths. The Q-BICs are induced from two types of electric quadrupole (EQ), for which detuning can be flexibly controlled by manipulating the C4v symmetry breaking Δd. The giant Rabi splitting in our proposed metasurface performs more than 15 times of the previous works, which provides more possibilities for important nonlinear and quantum applications, such as nanolaser and quantum optics.

The value of SDC2 and Septin9 combined with serum tumor markers in early diagnosis of colorectal cancer.

OBJECTIVE: The aim of this study is to evaluate the significance of combined detection of Septin9 and syndecan-2 (SDC2) methylation markers and serum tumor markers for the early diagnosis of colorectal cancer. METHODS: A total of 116 patients diagnosed with colorectal cancer between December 2022 and February 2024 were designated as the colorectal cancer group. Additionally, 31 patients with colorectal adenoma were assigned to the adenoma group, while 44 individuals undergoing routine physical examinations were included in the control group. Concentrations of Septin9, SDC2, fecal occult blood (FOB), and four tumor markers-carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 724 (CA724)-were measured. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves for Septin9, SDC2, the four tumor markers, FOB, the combination of Septin9 and SDC2, and the combined use of all seven indicators (CEA, CA19-9, CA125, CA72-4, FOB, Septin9, and SDC2). RESULTS: The colorectal cancer group exhibited the highest positive rates for Septin9, SDC2, the four tumor markers, the combined detection of Septin9 and SDC2, and the combined detection of all seven indicators, compared to both the adenoma and control groups (P < 0.05). The adenoma group also showed higher positive rates than the control group (P < 0.05). For patients with stage I-III colorectal cancer, the positive rates for the combined detection of Septin9 and SDC2 were 81.3%, 78.9%, and 90.2%, respectively, surpassing those for the combined detection of the four tumor markers (43.8%, 55.3%, and 61.0%). Additionally, the positive rates for the two-gene combination in stage III colorectal cancer were higher than those for FOB (P < 0.05). The sensitivity and area under the curve (AUC) for SDC2 were 73.3% and 0.855, respectively, exceeding the sensitivity and AUC for the combined four tumor markers, which were 60.3% and 0.734 (P < 0.05). The combined detection of the two methylated genes demonstrated a sensitivity of 86.2% and an AUC of 0.908, outperforming both FOB and the combined detection of the four tumor markers (P < 0.05). CONCLUSION: The detection of SDC2 exhibits high sensitivity for colorectal cancer, and when combined with Septin9, it significantly enhances the diagnostic accuracy for early-stage colorectal cancer, offering substantial clinical value.

Ultrasomics differentiation of malignant and benign focal liver lesions based on contrast-enhanced ultrasound.

OBJECTIVES: To establish a nomogram for differentiating malignant and benign focal liver lesions (FLLs) using ultrasomics features derived from contrast-enhanced ultrasound (CEUS). METHODS: 527 patients were retrospectively enrolled. On the training cohort, ultrasomics features were extracted from CEUS and b-mode ultrasound (BUS). Automatic feature selection and model development were performed using the Ultrasomics-Platform software, outputting the corresponding ultrasomics scores. A nomogram based on the ultrasomics scores from artery phase (AP), portal venous phase (PVP) and delayed phase (DP) of CEUS, and clinical factors were established. On the validation cohort, the diagnostic performance of the nomogram was assessed and compared with seniorexpert and resident radiologists. RESULTS: In the training cohort, the AP, PVP and DP scores exhibited better differential performance than BUS score, with area under the curve (AUC) of 84.1-85.1% compared with the BUS (74.6%, P < 0.05). In the validation cohort, the AUC of combined nomogram and expert was significantly higher than that of the resident (91.4% vs. 89.5% vs. 79.3%, P < 0.05). The combined nomogram had a comparable sensitivity with the expert and resident (95.2% vs. 98.4% vs. 97.6%), while the expert had a higher specificity than the nomogram and the resident (80.6% vs. 72.2% vs. 61.1%, P = 0.205). CONCLUSIONS: A CEUS ultrasomics based nomogram had an expert level performance in FLL characterization.

Comparative Genomic Analysis of Asian Cultivated Rice and Its Wild Progenitor (Oryza rufipogon) Has Revealed Evolutionary Innovation of the Pentatricopeptide Repeat Gene Family through Gene Duplication.

The pentatricopeptide repeat (PPR) gene family is one of the largest gene families in land plants. However, current knowledge about the evolution of the PPR gene family remains largely limited. In this study, we performed a comparative genomic analysis of the PPR gene family in O. sativa and its wild progenitor, O. rufipogon, and outlined a comprehensive landscape of gene duplications. Our findings suggest that the majority of PPR genes originated from dispersed duplications. Although segmental duplications have only expanded approximately 11.30% and 13.57% of the PPR gene families in the O. sativa and O. rufipogon genomes, we interestingly obtained evidence that segmental duplication promotes the structural diversity of PPR genes through incomplete gene duplications. In the O. sativa and O. rufipogon genomes, 10 (~33.33%) and 22 pairs of gene duplications (~45.83%) had non-PPR paralogous genes through incomplete gene duplication. Segmental duplications leading to incomplete gene duplications might result in the acquisition of domains, thus promoting functional innovation and structural diversification of PPR genes. This study offers a unique perspective on the evolution of PPR gene structures and underscores the potential role of segmental duplications in PPR gene structural diversity.

Acute toxic encephalopathy following bromadiolone intoxication: a case report.

BACKGROUND: Clinically, bromadiolone poisoning is characterized by severe bleeding complications in various organs and tissues. Bromadiolone-induced toxic encephalopathy is extremely rare. Here, we report a special case of bromadiolone-induced reversible toxic encephalopathy in a patient who had symmetrical lesions in the deep white matter. CASE PRESENTATION: A 23-year-old woman mainly presented with dizziness, fatigue, alalia and unsteady gait after the ingestion of bromadiolone. The laboratory examinations showed normal coagulation levels. Brain magnetic resonance imaging (MRI) showed apparent diffusion restriction in the bilateral deep white matter. The clinical manifestations and MRI alterations were reversible within one month of treatment with vitamin K. The neuropsychological assessment showed no neurodegenerative changes at the 2-year follow-up. CONCLUSION: With the increased use of bromadiolone as a rodenticide, more cases of ingestion have been reported annually over the past several years. Bromadiolone-induced toxic encephalopathy has no special clinical manifestations and is potentially reversible with timely treatment. Because of the reversible restricted diffusion on diffusion-weighted images (DWI) and low apparent diffusion coefficient (ADC) values, transient intramyelinic cytotoxic oedema is thought to be the cause rather than persistent ischaemia. The underlying pathophysiological mechanism is still unknown and may be coagulant-independent. This clinical case extends the current knowledge about neurotoxicity in cases of bromadiolone poisoning and indicates that MRI is useful for the early detection of bromadiolone-induced toxic encephalopathy.

Efficacy of Combination Therapy with Actinomycin D and Methotrexate in the Treatment of Low-Risk Gestational Trophoblastic Neoplasia.

OBJECTIVES: We aimed to identify an optimal regimen for low-risk gestational trophoblastic neoplasia (LR-GTN) providing reduction in dosage and toxicity/side effects, enhancement of therapeutic efficacy, and a shorter treatment duration. METHODS: A total of 149 LR-GTN patients were enrolled in the affiliated Beijing Maternity Hospital of Capital Medical University from January 2014 to January 2017 and randomly divided into 3 groups with 50 cases in the methotrexate (MTX) group, 49 in actinomycin D (ACT-D) group, and 50 in ACT-D+MTX group. Follow-up recorded symptoms, physical and bimanual gynecological examinations, routine blood test, serum ß-HCG level, liver and renal functions, electrolytes, electrocardiogram before each treatment course, and pelvic and abdominal B-mode ultrasound or pelvic/abdominal/chest computed tomography. RESULTS: Serum complete remission (SCR) was 96.0, 87.8, and 83.7% for the ACT-D+MTX, ACT-D, and MTX groups, respectively, with SCR being highest in the ACT-D+MTX group, statistically higher than in the MTX group. Vomiting was the only side effect differing significantly by chemotherapy regimen, with a distinctly higher incidence in the ACT-D+MTX group compared with the MTX group (p = 0.028). The reduction rate of serum ß-HCG in the ACT-D+MTX group was significantly greater than in the other 2 groups. CONCLUSION: Combined ACT-D+MTX chemotherapy achieved overall better efficacy and showed less toxicity than ACT-D or MTX alone, and thus can be prioritized for the treatment of LR-GTN.

High prevalence of Bacillus subtilis-infecting bacteriophages in soybean-based fermented foods and its detrimental effects on the process and quality of Cheonggukjang.

While the detrimental effect of bacteriophages on lactic acid bacterial fermentation is well documented, the importance of Bacillus subtilis phages in soybean-based fermented foods is not. In this study, we show for the first time that 100% of Korean soybean-based fermented foods (Doenjang, Gochujang, and Cheonggukjang) and 70% of raw materials (Meju and rice straw) were contaminated with B. subtilis-infecting phages (as high as 3.7 × 104 PFU g-1). Among 15 isolated B. subtilis-infecting phages, BSP18 was selected for further studies due to its specificity to and relatively broad host infectivity (34%) against B. subtilis. This Myoviridae family phage, BSP18 could infect all of the tested wild-type and commercially-used strains for soybean-based fermented food preparation. Furthermore, artificial contamination of as low as 102 PFU g-1 of BSP18 significantly inhibited B. subtilis growth during Cheonggukjang fermentation. Moreover, phage-treated samples contained considerably more degraded γ-PGA which could negatively affect the functional property of Cheonggukjang. We also present the data, strongly suggesting BSP18-encoded, not bacterial, γ-PGA hydrolase was responsible for γ-PGA degradation. In conclusion, B. subtilis phages are widespread in Korean soybean-based fermented foods and it should be of great concern as phages may hamper the bacterial growth during fermentation and yield poor quality products.

Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress.

Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P < 0.01). Basal expressions of HO-1 and Nrf-2 proteins were found in normal brain tissue. CO poisoning could activate HO-1/Nrf-2 pathway, start oxidative stress response. After the administration of Edaravone, the expression of HO-1 and Nrf-2 significantly increased (P < 0.01). These findings suggest that Edaravone may inhibit apoptosis, activate the Keapl-Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning.

Prostatic arterial embolization for the treatment of lower urinary tract symptoms due to large (>80 mL) benign prostatic hyperplasia: results of midterm follow-up from Chinese population.

BACKGROUND: Currently, large prostate size (>80 mL) of benign prostatic hyperplasia (BPH) still pose technical challenges for surgical treatment. This prospective study was designed to explore the safety and efficacy of prostatic arterial embolization (PAE) as an alternative treatment for patients with lower urinary tract symptoms (LUTS) due to largeBPH. METHODS: A total of 117 patients with prostates >80 mL were included in the study; all were failure of medical treatment and unsuited for surgery. PAE was performed using combination of 50-µm and 100-µm particles in size, under local anaesthesia by a unilateral femoral approach. Clinical follow-up was performed using the international prostate symptoms score (IPSS), quality of life (QoL), peak urinary flow (Qmax), post-void residual volume (PVR), international index of erectile function short form (IIEF-5), prostatic specific antigen (PSA) and prostatic volume (PV) measured by magnetic resonance (MR) imaging, at 1, 3, 6 and every 6 months thereafter. RESULTS: The prostatic artery origins in this study population were different from previously published results. PAE was technically successful in 109 of 117 patients (93.2%). Follow-up data were available for the 105 patients with a mean follow-up of 24 months. The clinical improvements in IPSS, QoL, Qmax, PVR, and PV at 1, 3, 6, 12, and 24 months was 94.3%, 94.3%, 93.3%, 92.6%, and 91.7%, respectively. The mean IPSS (pre-PAE vs post-PAE 26.0 vs 9.0; P < .0.01), the mean QoL (5.0 vs 3.0; P < 0.01), the mean Qmax (8.5 vs 14.5; P < 0.01), the mean PVR (125.0 vs 40.0; P < 0.01), and PV (118.0 vs 69.0, with a mean reduction of 41.5%; P < 0.01 ) at 24-month after PAE were significantly different with respect to baseline. The mean IIEF-5 was not statistically different from baseline. No major complications were noted. CONCLUSIONS: PAE is a safe and effective treatment method for patients with LUTS due to large volume BPH. PAE may play an important role in patients in whom medical therapy has failed, who are not candidates for open surgery or TURP or refuse any surgical treatment.

[Plant Diversity Changes and Its Driving Factors of Abandoned Land at Different Restoration Stages in the Middle of the Qinling Mountains].

The process of vegetation restoration is often accompanied by significant changes in aboveground plant diversity. To explore the driving mechanism of litter nutrient-soil nutrient-enzyme activity stoichiometry on aboveground vegetation change is of great importance for maintaining regional biodiversity conservation and ecological stability. Taking typical abandoned farmland of different restoration years （1， 8， 16， 31， and 50 a） in the Qinling Mountains as the research object， the variation characteristics of plant community diversity during vegetation restoration were analyzed through field investigation. Litter nutrients， soil nutrients， and the activities of five extracellular enzymes， including ß-1，4-glucosidase （BG）， cellobiohydrolase （CBH）， ß-1，4-N-acetylglucosaminidase （NAG）， leucine aminopeptidase （LAP）， and acid phosphatase （AP）， were determined. The characteristics of litter nutrients， soil nutrients， and enzyme stoichiometric ratios during vegetation restoration and the driving mechanism of plant diversity changes were discussed. The results showed that the plant community diversity index firstly decreased and then increased with the increase in vegetation restoration years， and the minimum was reached at 16 years after restoration. The results of principal component analysis showed that there were significant differences between total plant community diversity index and litter-soil-enzyme stoichiometric characteristics in different years of vegetation restoration. The plant community diversity index had a strong positive correlation with litter C∶P ratio and litter N∶P ratio but had a negative correlation with soil enzyme C∶P ratio （EEA C∶P）. The results of redundancy analysis showed that soil EEA C∶P had the highest explanation rate of plant diversity changes during vegetation restoration （25.93%）， followed by soil TP （5.94%）， which was the key factor regulating plant diversity changes. In conclusion， plant species and quantity increased significantly in abandoned farmland in the middle part of the Qinling Mountains at the late stage of vegetation restoration. Changes in the soil environment affected microbial metabolic activities and thus changed enzyme activities. Litter-soil-soil extracellular enzymes affected the community environment and plant diversity through feedback and regulation. EEA C∶P and TP were the main driving factors of aboveground plant diversity change during vegetation restoration.

ZIF-8-Modified Black Phosphorus Nanosheets Incorporated into Injectable Dual-Component Hydrogels for Enhanced Photothermal Antibacterial and Osteogenic Activities.

The development of growth factor-free biomaterials for bone tissue regeneration with anti-infection and anti-inflammatory activities remains challenging. Black phosphorus nanosheets (BPNs), with distinctive attributes, including photothermal conversion and calcium ion chelation, offer potential for use in bone tissue engineering and infection prevention. However, BPNs are prone to oxidation and degradation in aqueous environments, and methods to stabilize BPNs for long-term bone repair remain insufficient. Herein, zeolitic imidazolate framework-8 (ZIF-8) was used to stabilize BPNs via in situ crystallization onto the surface of BPNs (BP@ZIF-8 nanocomposite). A novel injectable dual-component hydrogel comprising gelatin methacryloyl (GelMA) and methacrylate-modified hyaluronic acid (HAMA) was used as a BP@ZIF-8 nanocomposite carrier (GelMA/HAMA/BP@ZIF-8). The BP@ZIF-8 nanocomposite could effectively protect internal BPNs from oxidation and enhance the long-term photothermal performance of the hydrogel in both in vitro and in vivo settings. The GelMA/HAMA/BP@ZIF-8 hydrogel was injectable and exhibited outstanding performance for photothermal conversion, mechanical strength, and biodegradability, as well as excellent photothermal antibacterial activity against Staphylococcus aureus and Escherichia coli in vitro and in an in vivo rat model. The GelMA/HAMA/BP@ZIF-8 hydrogel also provided a microenvironment conducive to osteogenic differentiation, promoting the transformation of M2 macrophages and inhibiting inflammatory responses. Furthermore, the hydrogel promoted bone regeneration and had a synergistic effect with near-infrared irradiation in a rat skull-defect model. Transcriptome sequencing analysis revealed that the PI3K-AKT- and calcium-signaling pathways may be involved in promoting osteogenic differentiation induced by the GH-BZ hydrogel. This study presents an innovative, multifaceted solution to the challenges of bone tissue regeneration with antibacterial and anti-inflammatory effects, providing insights into the design of smart biomaterials with dual therapeutic capabilities.

Characterisation of corrosion-induced crack in concrete using ultrasonic diffuse coda wave.

Corrosion damage in reinforcing steel bars has been a major cause of cracking and spalling of reinforced concrete. To extend the service life of concrete structures, non-destructive testing methods are necessary to assess the corrosion status in order to conduct a timely repair. At the early stage of corrosion, rust grows from the reinforcing bar, subsequently generates cracks towards the surface of the concrete. Ultrasonic methods have been widely used to detect cracks in concrete. However, it is challenging to characterise them due to the heterogeneous material properties of the concrete. In this paper, ultrasonic imaging technique based on diffuse coda wave has been explored to inspect and characterise corrosion-induced cracks. In this method, scattering cross-section of the crack is reconstructed with the Locadiff imaging technique. Based on the assumption that both crack tips have the same scattering cross-section, the size of the crack can be estimated when the location of the reinforcing bar is known. Numerical simulations were carried out to image straight and curved cracks, showing excellent accuracy. Experiments were designed subsequently on concrete samples with accelerated corrosion. The induced cracks were characterised by the proposed ultrasonic method, and compared with X-ray CT results, showing very good agreement.

Improved electroluminescence efficiency derived from functionalized decoration of 1,3,4-oxadiazole (OXD)-based Ir(III) complexes.

The performance of organic light emitting devices (OLEDs) fabricated using Ir(III) complexes bearing 1,3,4-oxadiazole (OXD)-based cyclometallic ligands still needs to be improved. In this work, Ir3+ was coordinated with a 2-(9,9-diethyl-9H-fluoren-2-yl)-1,3,4-oxadiazole (F-OXD) fragment, which was modified with various functionalized substituents, including fluorenyl, OXD and carbazolyl groups. Three complexes, named Ir-Flu, Ir-OXD and Ir-Cz, were synthesized successfully and their photophysical, electrochemical and electroluminescence properties were investigated in detail. All these complexes exhibited yellow-orange emission in solution and a distinct aggregation-induced phosphorescent emission (AIPE) phenomenon was observed. Monochrome OLEDs were fabricated using these phosphorescent dopants, and the turn-on voltage (V), luminance (L) and current efficiency (CE) showed significant improvement compared to analogous OXD-based Ir(III) complexes reported before. In particular, the device with Ir-OXD as the dopant achieved the highest maximum brightness of 25 014 cd m-2 and the lowest efficiency roll-off (42.6%) at the maximum luminance among all the devices. These results provided a proven strategy of functionalized decoration of OXD-based complexes to achieve superior luminous efficiency devices.

Purine nucleosidase (PNase) activity, probiotics potential, and food applicability of a newly-isolated Levilactobacillus brevis LAB42.

Hyperuricemia, a condition characterized by elevated levels of uric acid in the blood, is known as a risk factor for gout disease. In this study, we isolated a total of 72 MRS-grown colonies and evaluated their purine nucleosidase (PNase) activity. Among the isolated bacteria, Levilactobacillus (L.) brevis LAB42 displayed the highest PNase activity. Our findings also indicate that PNase activity can vary among lactic acid bacterial strains and during different growth phases. Based on the kinetics study, LAB42 consistently exhibits the highest PNase activity. Due to its ability to attach to Caco-2 cells and its resistance to acidic environments and bile exposure, L. brevis LAB42 was chosen for further studies and showed that with the right combination of additives, it has the potential to be an appropriate starter for milk fermentation.

Untargeted Metabolomics and Physicochemical Analysis Revealed the Quality Formation Mechanism in Fermented Milk Inoculated with Lactobacillus brevis and Kluyveromyces marxianus Isolated from Traditional Fermented Milk.

Traditional fermented milk from the western Sichuan plateau of China has a unique flavor and rich microbial diversity. This study explored the quality formation mechanism in fermented milk inoculated with Lactobacillus brevis NZ4 and Kluyveromyces marxianus SY11 (MFM), the dominant microorganisms isolated from traditional dairy products in western nan. The results indicated that MFM displayed better overall quality than the milk fermented with L. brevis NZ4 (LFM) and K. marxianus SY11 (KFM), respectively. MFM exhibited good sensory quality, more organic acid types, more free amino acids and esters, and moderate acidity and ethanol concentrations. Non-targeted metabolomics showed a total of 885 metabolites annotated in the samples, representing 204 differential metabolites between MFM and LFM and 163 between MFM and KFM. MFM displayed higher levels of N-acetyl-L-glutamic acid, cysteinyl serine, glaucarubin, and other substances. The differential metabolites were mainly enriched in pathways such as glycerophospholipid metabolism, arginine biosynthesis, and beta-alanine metabolism. This study speculated that L. brevis affected K. marxianus growth via its metabolites, while the mixed fermentation of these strains significantly changed the metabolism pathway of flavor-related substances, especially glycerophospholipid metabolism. Furthermore, mixed fermentation modified the flavor and quality of fermented milk by affecting cell growth and metabolic pathways.

Mendelian Randomization Study of Heart Failure and Stroke Subtypes.

Background: Whether heart failure (HF) is an independent risk factor of ischemic stroke (IS) and hemorrhagic stroke remains controversial. We employed a multivariable Mendelian randomization (MR) to further investigate the causal effects of HF on the risk of stroke and stroke subtypes. Methods: Genetically predicted HF was selected as an instrumental variable (IV) from published genome-wide association studies (GWAS) meta-analyses. Stroke data with different etiologies were extracted as outcome variables from another two GWAS meta-analyses. The random-effects inverse variance-weighted (IVW) model was applied as the main method, along with sensitivity analysis. Atrial fibrillation (AF), coronary heart disease (CHD), and systolic blood pressure (SBP) were controlled for mediating effects in multivariable MR. Results: Genetically predicted HF was significantly associated with any IS [odds ratio (OR), 1.39; 95% CI, 1.12-1.74; p = 0.03], large artery stroke (LAS; OR, 1.84; 95% CI, 1.27-2.65; p = 0.001), and cardioembolic stroke (CES; OR, 1.73; 95% CI, 1.21-2.47; p = 0.003), but without small vessel stroke (SVS; OR, 1.1; 95% CI, 0.80-1.52; p = 0.56) and intracerebral hemorrhage (ICH; OR, 0.86; 95% CI, 0.41-1.83; p = 0.699) in univariable MR. However, these significant associations were attenuated to the null after adjusting for confounding factor in multivariable MR. Conclusion: There was no direct causal association between HF and stroke in our study. The association between HF and IS can be driven by AF, CHD, and SBP.

Identification of Bacterial Pathogens at Genus and Species Levels through Combination of Raman Spectrometry and Deep-Learning Algorithms.

The rapid and accurate identification of the causing agents during bacterial infections would greatly improve pathogen transmission, prevention, patient care, and medical treatments in clinical settings. Although many conventional and molecular methods have been proven to be efficient and reliable, some of them suffer technical biases and limitations that require the development and application of novel and advanced techniques. Recently, due to its cost affordability, noninvasiveness, and label-free feature, Raman spectroscopy (RS) is emerging as a potential technique for fast bacterial detection. However, the method is still hampered by many technical issues, such as low signal intensity, poor reproducibility, and standard data set insufficiency, among others. Thus, it should be cautiously claimed that Raman spectroscopy could provide practical applications in real-world settings. In order to evaluate the implementation potentials of Raman spectroscopy in the identification of bacterial pathogens, we investigated 30 bacterial species belonging to 9 different bacterial genera that were isolated from clinical samples via surfaced enhanced Raman spectroscopy (SERS). A total of 17,149 SERS spectra were harvested from a Raman spectrometer and were further analyzed via machine learning approaches, which showed that a convolutional neural network (CNN) deep learning algorithm achieved the highest prediction accuracy for recognizing pathogenic bacteria at both the genus and species levels. In summary, the SERS technique holds a promising potential for fast bacterial pathogen identification in clinical laboratories with the integration of machine learning algorithms, which might be further developed and sharpened for the direct identification and prediction of bacterial pathogens from clinical samples. IMPORTANCE In this study, we investigated 30 bacterial species belonging to 9 different bacterial genera that were isolated from clinical samples via surfaced enhanced Raman spectroscopy (SERS). A total of 17,149 SERS spectra were harvested from a Raman spectrometer and were further analyzed via machine learning approaches, the results of which showed that the convolutional neural network (CNN) deep learning algorithm could achieve the highest prediction accuracy for recognizing pathogenic bacteria at both the genus and species levels. Taken together, we concluded that the SERS technique held a promising potential for fast bacterial pathogen diagnosis in clinical laboratories with the integration of deep learning algorithms, which might be further developed and sharpened for the direct identification and prediction of bacterial pathogens from clinical samples.

[Extracellular Enzyme Stoichiometry and Microbial Metabolism Limitation During Vegetation Restoration Process in the Middle of the Qinling Mountains, China].

Clarifying the characteristics of soil microbial nutrient limitation and its driving mechanisms during vegetation restoration after farmland abandonment has important implications for revealing soil nutrient cycling and maintaining ecosystem stability. To determine the limitation of soil microbial nutrients and its relationship with soil properties along a chronosequence of abandoned farmland in the middle of the Qinling Mountains, the soil physicochemical properties and five enzyme activities (ß-1,4-glucosidase (BG), cellobiohydrolase (CBH), ß-1,4-N-acetylglucosaminidase (NAG), leucine aminopeptidase (LAP), and acid phosphatase (AP)) were measured, and models of extracellular enzymatic activity were applied. The results showed that the activities of BG, CBH, NAG, LAP, and AP were significantly increased following farmland abandonment. With the increasing years of abandonment, the ratios of (BG+CBH)/(NAG+LAP) and (BG+CBH)/AP significantly decreased, whereas the ratio of (NAG+LAP)/AP increased. Correlation analysis showed that most soil physicochemical properties were significantly correlated with extracellular enzyme activities and extracellular enzymatic stoichiometry. The vector length of extracellular enzymatic stoichiometry decreased with the increase in abandonment years, indicating that the limitation of soil microorganisms on carbon (C) was reduced. Moreover, the vector angles (>45°) showed a decreasing trend, indicating that microbial metabolisms were limited by phosphorus (P) and gradually decreased. Regression analysis showed that the C and P limitations were significantly related to total nutrients, available nutrients, nutrient ratio, and soil physical properties. Partial least squares path modeling (PLS-PM) revealed that the C and P limitations were directly regulated by nutrient ratio. PLS-PM further showed that soil total nutrients indirectly affected soil microbial C and P limitations by affecting nutrient ratio, and nutrient ratio affected the soil metabolism limitation via available nutrients and pH. Our study suggests that the characteristics of microbial metabolism during the vegetation restoration process reflect the mechanism of microorganism-mediated soil nutrient cycling, which provides a theoretical basis for revealing the community dynamics and stability during the vegetation restoration process and maintaining the regional ecological environment security in the Qinling Mountains.

Prevalence, Diversity and UV-Light Inducibility Potential of Prophages in Bacillus subtilis and Their Possible Roles in Host Properties.

Bacillus subtilis is an important bacterial species due to its various industrial, medicinal, and agricultural applications. Prophages are known to play vital roles in host properties. Nevertheless, studies on the prophages and temperate phages of B. subtilis are relatively limited. In the present study, an in silico analysis was carried out in sequenced B. subtilis strains to investigate their prevalence, diversity, insertion sites, and potential roles. In addition, the potential for UV induction and prevalence was investigated. The in silico prophage analysis of 164 genomes of B. subtilis strains revealed that 75.00% of them contained intact prophages that exist as integrated and/or plasmid forms. Comparative genomics revealed the rich diversity of the prophages distributed in 13 main clusters and four distinct singletons. The analysis of the putative prophage proteins indicated the involvement of prophages in encoding the proteins linked to the immunity, bacteriocin production, sporulation, arsenate, and arsenite resistance of the host, enhancing its adaptability to diverse environments. An induction study in 91 B. subtilis collections demonstrated that UV-light treatment was instrumental in producing infective phages in 18.68% of them, showing a wide range of host specificity. The high prevalence and inducibility potential of the prophages observed in this study implies that prophages may play vital roles in the B. subtilis host.

Clinical outcomes and safety of apatinib monotherapy in the treatment of patients with advanced epithelial ovarian carcinoma who progressed after standard regimens and the analysis of the VEGFR2 polymorphism.

The aims of the present study were to investigate the clinical outcomes and safety of apatinib monotherapy in the treatment of patients with advanced epithelial ovarian carcinoma (EOC) who have progressed after standard regimens, and to analyze the vascular endothelial growth factor receptor 2 (VEGFR2) rs2071559 polymorphism. A total of 118 patients with advanced EOC who received apatinib treatment were included in the study. Tumor response was evaluated using progression-free survival (PFS) and overall survival (OS) time, and safety data were documented. Additionally, peripheral blood and peripheral blood mononuclear cell (PBMC) specimens from the patients with EOC were collected to perform the genotyping of genetic polymorphism and assess the mRNA expression of VEGFR2, respectively. The objective response rate across the 118 patients with advanced EOC was 38.98%, the disease control rate was 63.56%, the median PFS time was 4.65 months and the median OS time was 15.10 months. Regarding the polymorphism analysis, the prevalence of rs2071559 in VEGFR2 among the 118 patients with advanced EOC was recorded as the TT genotype in 72 cases (61.02%), TC genotype in 41 cases (34.75%) and CC genotype in 5 cases (4.23%), and the minor allele frequency of rs2071559 was 0.22. The distribution of the three genotypes was in accordance with the Hardy-Weinberg equilibrium (P=0.781). TC and CC genotypes were merged in the subsequent analysis. The prognosis analyses suggested that the median PFS time of patients with the TC/CC genotype and the TT genotype was 3.10 and 5.40 months, respectively (P=0.015). Moreover, the median OS time of the two genotypes was 12.60 and 17.50 months, respectively (P=0.009). However, no association was noted between genotype status of the polymorphism and adverse reactions. Additionally, the mRNA expression analysis indicated that the mRNA expression levels of VEGFR2 in PBMC specimens were significantly different between TT and TC/CC genotypes (P<0.001). The present study suggested that the clinical outcomes of patients with advanced EOC, who progressed after standard regimens and received apatinib treatment, might be influenced by the VEGFR2 rs2071559 polymorphism.