The effect of fecal microbiota transplantation on antibiotic-associated diarrhea and its impact on gut microbiota.

BACKGROUND: Antibiotic-associated diarrhea (AAD) refers to symptoms of diarrhea that cannot be explained by other causes after the use of antibiotics. AAD is thought to be caused by a disruption of intestinal ecology due to antibiotics. Fecal Microbiota Transplantation (FMT) is a treatment method that involves transferring microbial communities from the feces of healthy individuals into the patient's gut. METHOD: We selected 23 AAD patients who received FMT treatment in our department. Before FMT, we documented patients' bowel movement frequency, abdominal symptoms, routine blood tests, and inflammatory markers, and collected fecal samples for 16S rRNA sequencing to observe changes in the intestinal microbiota. Patients' treatment outcomes were followed up 1 month and 3 months after FMT. RESULTS: Out of the 23 AAD patients, 19 showed a clinical response to FMT with alleviation of abdominal symptoms. Among them, 82.61% (19/23) experienced relief from diarrhea, 65% (13/20) from abdominal pain, 77.78% (14/18) from abdominal distension, and 57.14% (4/7) from bloody stools within 1 month after FMT. Inflammatory markers IL-8 and CRP significantly decreased after FMT, but there were no noticeable changes in WBC, IL-6, and TNF-α before and after transplantation. After FMT, the abundance of Bacteroides and Faecalibacterium increased in patients' fecal samples, while the abundance of Escherichia-Shigella and Veillonella decreased. CONCLUSION: FMT has a certain therapeutic effect on AAD, and can alleviate abdominal symptoms and change the intestinal microbiota of patients.

Porous Se@SiO2 nanocomposites play a potential inhibition role in hyperoxaluria associated kidney stone by exerting antioxidant effects.

Background: Nephrolithiasis seriously affects people's health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. Methods: We synthesized the Se@SiO2 nanocomposites as described in Zhu's study. The size and morphology of the Se@SiO2 nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO2 group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO2 group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. Results: The CCK-8 assays showed that Se@SiO2 nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO2 groups (Se@SiO2 6.905±0.074 mg/kg; GAM + Se@SiO2 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO2 nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Conclusions: Se@SiO2 nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.

Photocatalytic Generation of Carbocation from Thiols and Application to Cross-Nucleophile Coupling.

Represented herein is a simple thiol identified as an effective precursor to photochemically form a carbocation. Thanks to the thiyl radical rapid transformation to disulfide, which serves not only to stabilize the generated thiyl radical but also to allow the second electron transfer to form a carbocation. The resulting carbocations, including primary benzylic, secondary, and tertiary carbocations, can smoothly couple with nitrogen, oxygen, and carbon nucleophilic coupling partners as well as complex drug molecules, accompanied by elemental sulfur formation in air.

Advancements in Polymer-Assisted Layer-by-Layer Fabrication of Wearable Sensors for Health Monitoring.

Recent advancements in polymer-assisted layer-by-layer (LbL) fabrication have revolutionized the development of wearable sensors for health monitoring. LbL self-assembly has emerged as a powerful and versatile technique for creating conformal, flexible, and multi-functional films on various substrates, making it particularly suitable for fabricating wearable sensors. The incorporation of polymers, both natural and synthetic, has played a crucial role in enhancing the performance, stability, and biocompatibility of these sensors. This review provides a comprehensive overview of the principles of LbL self-assembly, the role of polymers in sensor fabrication, and the various types of LbL-fabricated wearable sensors for physical, chemical, and biological sensing. The applications of these sensors in continuous health monitoring, disease diagnosis, and management are discussed in detail, highlighting their potential to revolutionize personalized healthcare. Despite significant progress, challenges related to long-term stability, biocompatibility, data acquisition, and large-scale manufacturing are still to be addressed, providing insights into future research directions. With continued advancements in polymer-assisted LbL fabrication and related fields, wearable sensors are poised to improve the quality of life for individuals worldwide.

Retinal Ischemic Perivascular Lesion Reflects Cerebral Small Vessel Disease Burden in Single Subcortical Infarction.

BACKGROUND: Retinal ischemic perivascular lesions (RIPLs) are an indicator of ischemia in the middle retina. We aimed to determine the relationship between RIPLs and single subcortical infarction (SSI). We also investigated the differences in cerebral small vessel disease imaging burden between groups with and without RIPLs in SSI. METHODS AND RESULTS: In this case-control study, we enrolled 82 patients with SSI and 72 nonstroke controls. All participants underwent magnetic resonance imaging and swept-source optical coherence tomography/optical coherence tomography angiography. Small vessel disease markers such as lacunes, cerebral microbleeds, white matter hyperintensity, and perivascular spaces were rated on brain imaging. RIPLs were assessed via swept-source optical coherence tomography. Optical coherence tomography angiography was used to measure the superficial vascular complex and deep vascular complex of the retina. After adjusting for risk factors, the presence of RIPLs was significantly associated with SSI (odds ratio [OR], 1.506 [95% CI, 1.365-1.662], P<0.001). Eyes with RIPLs showed lower deep vascular complex density (P=0.035) compared with eyes without RIPLs in patients with SSI. After adjusting for vascular risk factors, the presence of RIPLs in patients with SSI was associated with an increased periventricular white matter hyperintensity burden (ß=0.414 [95% CI, 0.181-0.647], P<0.001) and perivascular spaces-basal ganglia (ß=0.296 [95% CI, 0.079-0.512], P=0.008). CONCLUSIONS: RIPLs are associated with SSI independent of underlying risk factors. The relationship between the presence of RIPLs and small vessel disease markers provides evidence that RIPLs might be an additional indicator of cerebral ischemic changes.

Three-dimensional unmanned aerial vehicle path planning utilizing artificial gorilla troops optimizer incorporating combined mutation and quadratic interpolation operators.

In real terrain and dynamic obstacle scenarios, the complexity of the 3D UAV path planning problem greatly increases. Thus, to procure the optimal flight path for UAVs in such scenarios, an augmented Artificial Gorilla Troops Optimizer, denoted as OQMGTO, is proposed. The proposed OQMGTO algorithm introduces three strategies: combination mutation, quadratic interpolation, and random opposition-based learning, aiming to enhance the ability to timely escape from local optimal path areas and rapidly converge to the global optimal path. Given the flight distance, smoothness, terrain collision, and other five realistic factors of UAVs, specific constraint conditions are proposed to address complex scenarios, aiming to construct a path planning model. By optimizing this model, OQMGTO algorithm solves the path planning problem in complex scenarios. The extensive validation of OQMGTO algorithm on CEC2017 test suite enhances its credibility as a powerful optimization tool. Comparison experiments are conducted in simulated terrain scenarios, including six multi-obstacle terrain scenarios and three dynamic obstacle scenarios. The experimental findings validate OOMGTO algorithm can assist UAV in searching for excellent flight paths, featuring high safety and reliability characteristics, which confirms the superiority of OOMGTO algorithm for path planning in simulated terrain scenarios. Furthermore, in four flight missions carried out in real terrains, OQMGTO algorithm demonstrates superior search performance, planning smooth trajectories without mountain collision.

Interfacial Charge Transfer Regulates Photoredox Catalysis.

Photoredox catalytic processes offer the potential for precise chemical reactions using light and materials. The central determinant is identified as interfacial charge transfer, which simultaneously engenders distinctive behavior in the overall reaction. An in-depth elucidation of the main mechanism and highlighting of the complexity of interfacial charge transfer can occur through both diffusive and direct transfer models, revealing its potential for sophisticated design in complex transformations. The fundamental photophysics uncover these comprehensive applications and offer a clue for future development. This research contributes to the growing body of knowledge on interfacial charge transfer in photoredox catalysis and sets the stage for further exploration of this fascinating area of research.

Concurrent Ammonia Synthesis and Alcohol Oxidation Boosted by Glutathione-Capped Quantum Dots under Visible Light.

Mother nature accomplishes efficient ammonia synthesis via cascade N2 oxidation by lightning strikes followed with enzyme-catalyzed nitrogen oxyanion (NOx -, x = 2,3) reduction. The protein environment of enzymatic centers for NOx --to-NH4 + process greatly inspires the design of glutathione-capped (GSH) quantum dots (QDs) for ammonia synthesis under visible light (440 nm) in tandem with plasma-enabled N2 oxidation. Mechanistic studies reveal that GSH induces positive shift of surface charge to strengthen the interaction between NOx - and QDs. Upon visible light irradiation of QDs, the balanced and rapid hole and electron transfer furnish GS·radicals for 2e-/2H+ alcohol oxidation and H·for 8e-/10H+ NO3 --to-NH4 + reduction simultaneously. For the first time, mmol-scale ammonia synthesis is realized with apparent quantum yields of 5.45% ± 0.64%, and gram-scale synthesis of value-added acetophenone and NH4Cl proceeds with 1:4 stoichiometry and stability, demonstrating promising multielectron and multiproton ammonia synthesis efficiency and sustainability with nature-inspired artificial photocatalysts.

Coregulatory effects of multiple histone modifications in key ferroptosis-related genes for lung adenocarcinoma.

Aim: The present study was designed to investigate the coregulatory effects of multiple histone modifications (HMs) on gene expression in lung adenocarcinoma (LUAD). Materials & methods: Ten histones for LUAD were analyzed using ChIP-seq and RNA-seq data. An innovative computational method is proposed to quantify the coregulatory effects of multiple HMs on gene expression to identify strong coregulatory genes and regions. This method was applied to explore the coregulatory mechanisms of key ferroptosis-related genes in LUAD. Results: Nine strong coregulatory regions were identified for six ferroptosis-related genes with diverse coregulatory patterns (CA9, PGD, CDKN2A, PML, OTUB1 and NFE2L2). Conclusion: This quantitative method could be used to identify important HM coregulatory genes and regions that may be epigenetic regulatory targets in cancers.

Effectiveness and safety of Qidong Huoxue decoction in treatment of acute lung injury and acute respiratory distress syndrome: a randomized, controlled trial.

OBJECTIVE: To evaluate the efficacy of Qidong Huoxue decoction (，QDHX) in treating acute lung injury and acute respiratory distress syndrome (ALI/ARDS) when used as an adjunctive treatment. METHODS: ALI/ARDS patients admitted to our medical intensive care unit were randomly allocated to the control group or the QDHX group and received standard therapy. The QDHX group received QDHX (50 mL per day for 14 d) orally or via a gastric tube. The primary outcome was measured according to Traditional Chinese Medicine (TCM) syndrome scores, with partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) levels as the secondary outcome. RESULTS: A total of 73 patients completed the study (36 in the TCM and 37 in the conventional group), and their records were analyzed. After 14-d treatment, the TCM group showed a significant decrease in TCM syndrome scores (P < 0.05) and increased PaO2/FiO2 levels (P < 0.05). The therapeutic effect of integrated Chinese and western medicine was more significant than that of Western Medicine alone. No serious side effects were observed. CONCLUSIONS: Our study results show that QDHX in combination with conventional drug therapy can significantly reduce some clinical symptoms in patients with ALI/ARDS.

Donor-recipient intermicrobial interactions impact transfer of subspecies and fecal microbiota transplantation outcome.

Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906). We found that interactions between donor and recipient microbes, which were overwhelmingly phylogenetically divergent, were important for subspecies transfer and positive clinical outcomes. Additionally, a donor-recipient SGB match was indicative of a high likelihood of strain transfer. Importantly, these ecodynamics were shared across FMT datasets encompassing multiple diseases. Collectively, these findings provide detailed insight into specific microbial interactions and dynamics that determine FMT success.

Association between functional network connectivity, retina structure and microvasculature, and visual performance in patients after thalamic stroke: An exploratory multi-modality study.

BACKGROUND AND OBJECTIVE: Neuro-ophthalmologic symptoms and retinal changes have been increasingly observed following thalamic stroke, and there is mounting evidence indicating distinct alterations occurring in the vision-related functional network. However, the intrinsic correlations between these changes are not yet fully understood. Our objective was to explore the altered patterns of functional network connectivity and retina parameters, and their correlations with visual performance in patients with thalamic stroke. METHODS: We utilized resting-state functional MRI to obtain multi-modular functional connectivity (FC), and optical coherence tomography-angiography to measure various retina parameters, such as the retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), superficial vascular complex (SVC), and deep vascular complex. Visual acuity (VA) was used as a metric for visual performance. RESULTS: We included 46 patients with first-ever unilateral thalamic stroke (mean age 59.74 ± 10.02 years, 33 males). Significant associations were found between FC of attention-to-default mode and SVC, RNFL, and GCIPL, as well as between FC of attention-to-visual and RNFL (p < .05). Both RNFL and GCIPL exhibited significant associations with FC of visual-to-visual (p < .05). Only GCIPL showed an association with VA (p = .038). Stratified analysis based on a disease duration of 6 months revealed distinct and significant linking patterns in multi-modular FC and specific retina parameters, with varying correlations with VA in each subgroup. CONCLUSION: These findings provide valuable insight into the neural basis of the associations between brain network dysfunction and impaired visual performance in patients with thalamic stroke. Our novel findings have the potential to inform future targeted and individualized therapies. However, further comprehensive studies are necessary to validate our results.

First Report of Ilyonectria coprosmae Causing Root Rot of Bletilla striata in Yunnan province of China.

Bletilla striata is a valuable medicine in China, belonging to the Orchidaceae family, and is used for treating various ailments such as hemoptysis, pyocutaneous disease, and anal fissure by preventing blood flow, reducing swelling, and promoting granulation. In June 2022, a disease with symptoms similar to root rot was observed on B. striata in the pineland (the area was 0.4 hectare) of Lancang County (22°48'17" N, 99°46'58"22 E), Yunnan Province, China. The root rot incidence rate reached 16% (Table S1). The root rot incidence was calculated as follows: root rot incidence (%) = (number of root rot seedlings/total number of seedlings investigated) × 100. In May 2023, the similar symptoms were observed in the field, and the disease incidence was 17% (Table S1). Initially, there were no obvious symptoms on the leaves. Subsequently, the leaves wilted and brown spots appeared. Later, the entire leaf browned, withered and eventually died (Fig. S1A, B). The roots were brown and the browning spread from the root edge to the center, causing vascular bundle browning and dead lignified fibers in the cortex (Fig. S1C, D). To isolate the causal pathogen, 20 symptomatic root tissues were collected from 20 plants. Cutting the diseased tissues into small pieces (0.5 × 0.5 cm). After surface sterilization (30s with 75% ethanol and 3 min with 2% sodium hypochlorite, rinsed three times with sterile water), the disinfected root tissues were plated onto potato dextrose agar (PDA) and incubated at 25℃ for 4 to 6 days with 12 h light/dark photoperiod. A total of 10 single-spore isolates with similar morphology and conidial characteristics were obtained. one representative isolate BJG6 was selected for identification and further study. The fungal colony was reddish-brown or orange-white on PDA after 8 days of incubation at 25℃. The mycelium was like carpet or cotton, and the edge of colony was uniform (Fig. S1E). Large conidia were formed on simple conidial peduncles (Fig. S1F, G). The conidia with 1~3 septates and 1 mostly, with cylindrical shapes and narrow tops but sharp bases (Fig. S1H-J). Conidia with 1 septate measured as 5.5 (4.3-6.7) × 20.7 (16.0-25.4) µm (n=30), while those with 2 septates measured as 6.6 (5.8-7.4) × 26.5 (21.7-31.3) µm (n=30), and those with 3 septates was 6.9 (6.2-7.8) × 31.8 (29.3-34.3) µm (n=30). Ellipsoidal microconidia could be formed on conidiophore and measured as 2.4 (1.9-2.9) × 4.9 (5.9-3.9) µm to 2.7 (2.2-3.2) × 5.4 (4.3-6.5) µm (n=30). Spherical or subspherical chlamydospores were produced on low-nutrient agar, with an average size of 5.8(5.0-6.6) µm×5.3 (4.4-6.2) µm (n=30) (Fig. S1K, L). According to the morphology and conidial features, the pathogen was consistent with the description of Ilyonectria coprosmae (Cabral et al. 2012). The total genomic DNA was extracted, and primer pairs ITS4/ITS5 were used to amplify and sequence the rDNA-ITS region (ITS1-5.8 S rRNA-ITS2 gene regions) (White et al. 1990). The sequences were deposited in GenBank (SUB13905750 for ITS). BLAST searches revealed BJG6 showed 98% homology with corresponding sequences of Ilyonectria coprosmae in GenBank (JF735260). A phylogenetic tree (MEGA 7.0) was constructed using maximum-likelihood methods (Fig. S2). To identify pathogenicity, a cultured medium in a size of 6mm containing isolate BJG6 was inoculated onto ten healthy roots of B. striata, PDA plugs alone were used as the uninoculated controls. All samples were placed in a dark inoculation chamber at 25℃. The pathogenicity test was replicated three times. After two weeks, all inoculated roots appeared similar symptoms identical to those observed on field plants (Fig. S1M, N-P), while control plants remained healthy (Fig. S1Q, R). The same pathogenic fungus was reisolated from the symptomatic root rot, and the characteristics of colony and conidia were the same as the original isolates (Fig. S1S, T). These results confirmed I. coprosmae as the causal pathogen of root rot disease on B. striata in China by Koch's postulates tests for the first time. Further exploration should be conducted to understand the occurrence and migration of this disease, so as to develop specific and efficient disease management strategies in the future.

Three cancers in the renal pelvis, bladder, and colon: A case report.

BACKGROUND: Multiple primary cancers are rare occurrences that can involve either metachronous or synchronous development. It is particularly rare for an individual to have more than two primary cancers. In this report, we present a case study of an elderly man who was diagnosed with three heterochronous cancers in the renal pelvis, bladder, and colon. CASE SUMMARY: On December 30, 2014, a 51-year-old Chinese man was admitted to our hospital with complaints of intermittent painless gross hematuria for the preceding week. A computed tomography (CT) scan revealed wall thickening in the left ureter's upper segment, while a CT urography revealed a left renal pelvis tumor. A successful laparoscopic radical resection of the left renal pelvis tumor was subsequently performed at Shanghai Zhongshan Hospital in January 2015. The pathological findings after the surgery revealed a low-grade papillary urothelial carcinoma of the renal pelvis. The final pathological tumor stage was pT1N0M0. After surgery, this patient received 6 cycles of intravenous chemotherapy with gemcitabine and carboplatin, as well as bladder infusion therapy with gemcitabine. On December 18, 2017, the patient was admitted once again to our hospital with a one-day history of painless gross hematuria. A CT scan showed the presence of a space-occupying lesion on the posterior wall of bladder. Cystoscopic examination revealed multiple tumors in the bladder and right cutaneous ureterostomy was performed under general anesthesia on December 29, 2017. The postoperative pathological findings disclosed multifocal papillary urothelial carcinoma of the bladder (maximum size 3.7 cm × 2.6 cm). The bladder cancer was considered a metastasis of the renal pelvis cancer after surgery. The pathological tumor stage was pT1N0M1. The patient refused chemotherapy after surgery. After another six years, the patient returned on February 28, 2023, complaining of periumbilical pain that had lasted six days. This time, a CT scan of the abdomen showed a tumor in the ascending colon, but a subsequent colonoscopy examination indicated a tumor in the descending colon. On March 12, 2023, a subtotal colectomy and an ileosigmoidal anastomosis were carried out under general anesthesia. Postoperative pathological findings revealed that all three tumors were adenocarcinomas. The final pathological tumor stage was pT3N0M0. The patient had an uneventful postoperative recovery and was discharged without complications. CONCLUSION: The case of this elderly man presents a rare occurrence of metachronous primary cancers in the renal pelvis and colon. Bladder cancer is considered a metastasis of renal pelvis cancer after surgery. Optimal treatment can be implemented by evaluating the patient's histological features, clinical history, and tumor distribution correctly.

Novel quantitative immunohistochemistry method using histone H3, family 3B as the internal reference standard for measuring human epidermal growth factor receptor 2 expression in breast cancer.

BACKGROUND: Immunohistochemistry (IHC) is an essential technique in surgical and clinical pathology for detecting diagnostic, prognostic, and predictive biomarkers for personalized cancer therapy. However, the lack of standardization and reference controls results in poor reproducibility, and a reliable tool for IHC quantification is urgently required. The objective of this study was to describe a novel approach in which H3F3B (histone H3, family 3B) can be used as an internal reference standard to quantify protein expression levels using IHC. METHODS: The authors enrolled 89 patients who had human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). They used a novel IHC-based assay to measure protein expression using H3F3B as the internal reference standard. H3F3B was uniformly expressed at the protein level in all tumor regions in cancer tissues. HER2 expression levels were measured with the H-score using HALO software. RESULTS: Kaplan-Meier analysis indicated that, among patients who had HER2-positive BC in The Cancer Genome Atlas data set and the authors' data set, the subgroup with low HER2 expression had a significantly better prognosis than the subgroup with high HER2 expression. Furthermore, the authors observed that HER2 expression levels were precisely evaluated using the proposed method, which can classify patients who are at higher risk of HER2-positive BC to receive trastuzumab-based adjuvant therapy. Dual-color IHC with H3F3B is an excellent tool for internal and external quality control of HER2 expression assays. CONCLUSIONS: The proposed IHC-based quantification method accurately assesses HER2 expression levels and provides insights for predicting clinical prognosis in patients with HER2-positive BC who receive trastuzumab-based adjuvant therapy.

Gluten-free diet on video platforms: Retrospective infodemiology study.

Background: Video platform is an important approach for individuals to access and adopt health information. Online information on gluten-free diet (GFD) videos remains underinvestigated. Methods: GFD videos were identified by hashtag-based searching strategy. Videos' basic information, engagement metrics, and content were recorded. Mann-Kendall test was performed to examine time trends of submitting videos and engagement metrics. Video quality was evaluated by the DISCERN instrument and the HONcode. Results: A total of 822 videos were included in the analysis, with the majority focusing on gluten-free food recipes. The number of videos related to GFD was showing an upward trend. Engagement metrics varied between platforms and video types, with non-recipe videos receiving higher user engagement. The average DISCERN score was 50.20 out of 80 and the average HONcode score was 1.93 out of 8. Videos submitted by health professionals demonstrated better quality compared to those submitted by patients or general users. Conclusion: There was a rise in the number of videos related to GFD on Chinese video platforms. The overall quality of these videos was poor, most of them were not rigorous enough. Highlighting using social media as a health information source has the potential risk of disseminating one-sided messages and misleading. Efforts should be made to enhance the transparency of advertisements and establish clear guidelines for information sharing on social media platforms.

Programmable Ferroelectricity in Hf0.5Zr0.5O2 Enabled by Oxygen Defect Engineering.

Ferroelectricity, especially the Si-compatible type recently observed in hafnia-based materials, is technologically useful for modern memory and logic applications, but it is challenging to differentiate intrinsic ferroelectric polarization from the polar phase and oxygen vacancy. Here, we report electrically controllable ferroelectricity in a Hf0.5Zr0.5O2-based heterostructure with Sr-doped LaMnO3, a mixed ionic-electronic conductor, as an electrode. Electrically reversible extraction and insertion of an oxygen vacancy into Hf0.5Zr0.5O2 are macroscopically characterized and atomically imaged in situ. Utilizing this reversible process, we achieved multilevel polarization states modulated by the electric field. Our study demonstrates the usefulness of the mixed conductor to repair, create, manipulate, and utilize advanced ferroelectric functionality. Furthermore, the programmed ferroelectric heterostructures with Si-compatible doped hafnia are desirable for the development of future ferroelectric electronics.

ECDEP: identifying essential proteins based on evolutionary community discovery and subcellular localization.

BACKGROUND: In cellular activities, essential proteins play a vital role and are instrumental in comprehending fundamental biological necessities and identifying pathogenic genes. Current deep learning approaches for predicting essential proteins underutilize the potential of gene expression data and are inadequate for the exploration of dynamic networks with limited evaluation across diverse species. RESULTS: We introduce ECDEP, an essential protein identification model based on evolutionary community discovery. ECDEP integrates temporal gene expression data with a protein-protein interaction (PPI) network and employs the 3-Sigma rule to eliminate outliers at each time point, constructing a dynamic network. Next, we utilize edge birth and death information to establish an interaction streaming source to feed into the evolutionary community discovery algorithm and then identify overlapping communities during the evolution of the dynamic network. SVM recursive feature elimination (RFE) is applied to extract the most informative communities, which are combined with subcellular localization data for classification predictions. We assess the performance of ECDEP by comparing it against ten centrality methods, four shallow machine learning methods with RFE, and two deep learning methods that incorporate multiple biological data sources on Saccharomyces. Cerevisiae (S. cerevisiae), Homo sapiens (H. sapiens), Mus musculus, and Caenorhabditis elegans. ECDEP achieves an AP value of 0.86 on the H. sapiens dataset and the contribution ratio of community features in classification reaches 0.54 on the S. cerevisiae (Krogan) dataset. CONCLUSIONS: Our proposed method adeptly integrates network dynamics and yields outstanding results across various datasets. Furthermore, the incorporation of evolutionary community discovery algorithms amplifies the capacity of gene expression data in classification.

Fast and sensitive differential diagnosis of pseudorabies virus-infected versus pseudorabies virus-vaccinated swine using CRISPR-Cas12a.

IMPORTANCE: Pseudorabies virus (PRV) causes high mortality and miscarriage rates in the infected swine, and the eradication policy coupled with large-scale vaccination of live attenuated vaccines has been adopted globally against PRV. Differential diagnosis of the vaccinated and infected swine is highly demanded. Our multienzyme isothermal rapid amplification (MIRA)-Cas12a detection method described in this study can diagnose PRV with a superior sensitivity comparable to the quantitative PCR (qPCR) and a competitive detection speed (only half the time as qPCR needs). The portable feature and the simple procedure of MIRA-Cas12a make it easier to deploy for clinical diagnosis, even in resource-limited settings. The MIRA-Cas12a method would provide immediate and accurate diagnostic information for policymakers to respond promptly.

GR-KLF15 pathway controls hepatic lipogenesis during fasting.

During periods of fasting, the body undergoes a metabolic shift from carbohydrate utilization to the use of fats and ketones as an energy source, as well as the inhibition of de novo lipogenesis and the initiation of gluconeogenesis in the liver. The transcription factor sterol regulatory element-binding protein-1 (SREBP-1), which plays a critical role in the regulation of lipogenesis, is suppressed during fasting, resulting in the suppression of hepatic lipogenesis. We previously demonstrated that the interaction of fasting-induced Kruppel-like factor 15 (KLF15) with liver X receptor serves as the essential mechanism for the nutritional regulation of SREBP-1 expression. However, the underlying mechanisms of KLF15 induction during fasting remain unclear. In this study, we show that the glucocorticoid receptor (GR) regulates the hepatic expression of KLF15 and, subsequently, lipogenesis through the KLF15-SREBP-1 pathway during fasting. KLF15 is necessary for the suppression of SREBP-1 by GR, as demonstrated through experiments using KLF15 knockout mice. Additionally, we show that GR is involved in the fasting response, with heightened binding to the KLF15 enhancer. It has been widely known that the hypothalamic-pituitary-adrenal (HPA) axis regulates the secretion of glucocorticoids and plays a significant role in the metabolic response to undernutrition. These findings demonstrate the importance of the HPA-axis-regulated GR-KLF15 pathway in the regulation of lipid metabolism in the liver during fasting.