Deep learning model to discriminate diverse infection types based on pairwise analysis of host gene expression.

Accurate detection of pathogens, particularly distinguishing between Gram-positive and Gram-negative bacteria, could improve disease treatment. Host gene expression can capture the immune system's response to infections caused by various pathogens. Here, we present a deep neural network model, bvnGPS2, which incorporates the attention mechanism based on a large-scale integrated host transcriptome dataset to precisely identify Gram-positive and Gram-negative bacterial infections as well as viral infections. We performed analysis of 4,949 blood samples across 40 cohorts from 10 countries using our previously designed omics data integration method, iPAGE, to select discriminant gene pairs and train the bvnGPS2. The performance of the model was evaluated on six independent cohorts comprising 374 samples. Overall, our deep neural network model shows robust capability to accurately identify specific infections, paving the way for precise medicine strategies in infection treatment and potentially also for identifying subtypes of other diseases.

Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio and wide clinical application are needed. Based on public data sets, the Chemotherapy Cohort and the Immunotherapy Cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion (TIDE) analysis, single-sample gene set enrichment analysis (ssGSEA), stemness index calculation, immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful to predict the prognosis of GC patients, the degree of chemotherapy resistance and the efficacy of immunotherapy.

Application of Hip Pericapsular Nerve Block Combined With Spinal Anesthesia in the Treatment of Elderly Patients With Femoral Intertrochanteric Fracture.

OBJECTIVE: To investigate the effect of pericapsular nerve group (PENG) block combined with spinal anesthesia in the treatment of elderly patients with intertrochanteric fractures through "rapid diagnosis and treatment channel" PFNA internal fixation. METHODS: 52 elderly patients were randomly divided into the observation group (26 patients, PENG block combined with spinal anesthesia) and the control group (26 patients, spinal anesthesia alone). The general health, mean arterial pressure (MAP), and heart rate (HR) of both groups were compared at various stages: immediately before the administration of pain analgesia, during the positioning of spinal epidural anesthesia, at the beginning and end of the surgery, and 2 hours after surgery. Additionally, VAS scores at rest and during passive straight leg elevation by 15° were evaluated at 12 hours, 24 hours, 48 hours, 72 hours, and 7 days after surgery. RESULTS: The MAP and HR in the observation group under spinal anesthesia in the lateral position were lower than those in the control group (P < 0.05). Additionally, the VAS scores of the observation group during positioning and at 12 hours and 24 hours after surgery were lower than those in the control group under spinal epidural anesthesia (both P < 0.05). CONCLUSION: The application of ultrasound-guided PENG block combined with lumbar anesthesia can reduce pain when in lateral position, stabilize perioperative vital signs, and result in high satisfaction.

The dynamics of N6-methyladenine RNA modification in resistant and susceptible rice varieties responding to rice stem borer damage.

N6-methyladenosine (m6A) is the most prevalent modification in cellular RNA which orchestrates diverse physiological and pathological processes during stress response. However, the differential m6A modifications that cope with herbivore stress in resistant and susceptible crop varieties remain unclear. Here, we found that rice stem borer (RSB) larvae grew better on indica rice (e.g., MH63, IR64, Nanjing 11) than on japonica rice varieties (e.g., Nipponbare, Zhonghua 11, Xiushui 11). Then, transcriptome-wide m6A profiling of representative resistant (Nipponbare) and susceptible (MH63) rice varieties were performed using a nanopore direct RNA sequencing approach, to reveal variety-specific m6A modifications against RSB. Upon RSB infestation, m6A methylation occurred in actively expressed genes in Nipponbare and MH63, but the number of methylation sites decreased across rice chromosomes. Integrative analysis showed that m6A methylation levels were closely associated with transcriptional regulation. Genes involved in herbivorous resistance related to mitogen-activated protein kinase, jasmonic acid (JA), and terpenoid biosynthesis pathways, as well as JA-mediated trypsin protease inhibitors, were heavily methylated by m6A, and their expression was more pronounced in RSB-infested Nipponbare than in RSB-infested MH63, which may have contributed to RSB resistance in Nipponbare. Therefore, dynamics of m6A modifications act as the main regulatory strategy for expression of genes involved in plant-insect interactions, which is attributed to differential responses of resistant and susceptible rice varieties to RSB infestation. These findings could contribute to developing molecular breeding strategies for controlling herbivorous pests.

Aggregation Enhanced Thermally Activated Delayed Fluorescence through Spin-Orbit Coupling Regulation.

Integrating aggregation-induced emission (AIE) into thermally activated delayed fluorescence (TADF) emitters holds great promise for the advancement of highly efficient organic light emitting diodes (OLEDs). Despite recent advancements, a thorough comprehension of the underlying mechanisms remains imperative for the practical application of such materials. In this work, we introduce a novel approach aimed at modulating the TADF process by manipulating dynamic processes in excited states through aggregation effect. Our findings reveal that aggregation not only enhances both prompt and delayed fluorescence simultaneously but also imposes constraints on molecular reorientation. This constraint reinforces spin-orbit coupling and reduces the energy gap between singlets and triplets. These insights deepen our understanding of the fundamental mechanisms governing the aggregation effect on TADF materials and provide valuable guidance for the design of high-efficiency photoluminescent materials.

A clinical and computed tomography-based nomogram to predict the outcome in patients with anterior circulation large vessel occlusion after endovascular mechanical thrombectomy.

PURPOSE: To explore the positive predictors of the clinical outcome in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (ACLVO) after endovascular mechanical thrombectomy (EMT) at a 90-day follow-up, and to establish a nomogram model to predict the clinical outcome. MATERIALS AND METHODS: AIS patients with ACLVO detected by multimodal Computed Tomography imaging who underwent EMT were collected. Patients were divided into the favorable and the unfavorable groups according to the 90-day modified Rankin Scale (mRS) score. Univariate and multivariate analyses were performed to investigate predictors of the favorable outcome (mRS of 0-2). A nomogram model for predicting the clinical outcome after EMT was drawn, and the receiver operating characteristic (ROC) curve was used to evaluate its predictive value. RESULTS: Totally 105 patients including 65 patients in the favorable group and 40 in the unfavorable group were enrolled. Multivariate logistic regression analysis showed that admission National Institute of Health Stroke scale (NIHSS) score [0.858 (95% CI 0.778-0.947)], ACLVO at M2 [20.023 (95% CI 2.204-181.907)] and infarct core (IC) volume [0.943 (95% CI 0.917-0.969)] was positively correlated with favorable outcome. The accuracy of the nomogram model in predicting the outcome was 0.923 (95% CI 0.870-0.976), with a cutoff value of 119.6 points. The area under the ROC curve was 0.848 (95% CI 0.780-0.917; sensitivity, 79.7%; specificity, 90.0%). CONCLUSION: A low Admission NIHSS score, ACLVO at M2, and a small IC volume were positive predictors for favorable outcome. The nomogram model may well predict the outcome in AIS patients with ACLVO after EMT.

Dissipationless layertronics in axion insulator MnBi2Te4.

Surface electrons in axion insulators are endowed with a topological layer degree of freedom followed by exotic transport phenomena, e.g., the layer Hall effect. Here, we propose that such a layer degree of freedom can be manipulated in a dissipationless way based on the antiferromagnetic [Formula: see text] with tailored domain structure. This makes [Formula: see text] a versatile platform to exploit the 'layertronics' to encode, process and store information. Importantly, the layer filter, layer valve and layer reverser devices can be achieved using the layer-locked chiral domain wall modes. The dissipationless nature of the domain wall modes makes the performance of the layertronic devices superior to those in spintronics and valleytronics. Specifically, the layer reverser, a layer version of the Datta-Das transistor, also fills up the blank in designing the valley reverser in valleytronics. Our work sheds light on constructing new generation electronic devices with high performance and low-energy consumption in the framework of layertronics.

A DIRIGENT Gene GmDIR26 Regulates Pod Dehiscence in Soybean.

Pod dehiscence brings much loss for modern agricultural production, and multiple pod dehiscence components have been identified in many plant species. However, the pod dehiscence regulation factors in soybean are limited. In this study, we investigate the function of GmDIR26, a close homologues gene of pod dehiscence genes GmPdh1, PvPdh1, and CaPdh1, in the regulation of pod dehiscence in soybean. The secondary and tertiary structure analysis reveals that GmDIR26 protein has a similar structure with GmPdh1, PvPdh1, and CaPdh1 proteins. Synteny analysis of soybean and chickpea genomes shows that the genomic region surrounding GmDIR26 and CaPdh1 might be evolved from the same ancestor, and these two genes might have similar function. GmDIR26 shows an increased expression pattern during pod development and reaches a peak at beginning seed stage. Meanwhile, GmDIR26 exhibits high expression levels in dorsal suture and pod wall, but low expression pattern in ventral suture. In addition, GmDIR26 shows higher expression levels in pod dehiscence genotype than that in pod indehiscence accessions. Overexpression of GmDIR26 in soybean increases pod dehiscence in transgenic plants, of which the lignin layer in inner sclerenchyma pods is thicker and looser. The expression levels of several pod dehiscence genes are altered. Our study provides important information for further modification of pod dehiscence resistance soybean and characterization of soybean pod dehiscence regulation network.

Investigation of 3D vessel reconstruction under Doppler imaging with phantoms: Towards reconstruction of the Circle of Willis.

BACKGROUND: Stroke is the second leading cause of death across the globe. Early screening and risk detection could provide early intervention and possibly prevent its incidence. Imaging modalities, including 1D-Transcranial Doppler Ultrasound (1D-TCD) or Transcranial Color-code sonography (TCCS), could only provide low spatial resolution or 2D image information, respectively. Notably, 3D imaging modalities including CT have high radiation exposure, whereas MRI is expensive and cannot be adopted in patients with implanted devices. This study proposes an alternative imaging solution for reconstructing 3D Doppler ultrasound geared towards providing a screening tool for the 3D vessel structure of the brain. METHODS: The system comprises an ultrasound phased array attached to a servo motor, which can rotate 180˚ at a speed of 2˚/s. We extracted the color Doppler ROI from the image before reconstructing it into a 3D view using a customized pixel-based algorithm. Different vascular diameters, flow velocity, and depth were tested using a vascular phantom with a pumped flow to confirm the system for imaging blood flow. These variables were set to mimic the vessel diameter, flow speed, and depth of the Circle of Willis (CoW) during a transcranial screening. RESULTS AND CONCLUSIONS: The lower values of absolute error and ratio were found in the larger vascular channels, and vessel diameter overrepresentation was observed. Under different flow velocities, such diameter overrepresentation in the reconstructed flow did not change much; however, it did change with different depths. Meanwhile, the setting of the velocity scale and the color gain affected the dimension of reconstructed objectives. Moreover, we presented a 3D image of CoW from a subject to demonstrate its potential. The findings of this work can provide a good reference for further studies on the reconstruction of the CoW or other blood vessels using Doppler imaging.

Experimental study on I/II/III mixed mode fracture characteristics of a combined rock mass under creep loading.

I/II/III mixed mode fractures of intersecting joint fissures often occur in natural rock masses, and jointed rock masses are prone to rockbursts in deep underground engineering when subjected to long-term crustal stresses. However, most studies of the mechanical mechanisms of these intersected joints have been conducted by simplifying two-dimensional joint model tests. Furthermore, the fracture mechanisms of two-dimensional intersected joints under tension and compression are completely different from those of three-dimensional joints. This paper presents a novel prefabricated specimen with combinations of intersecting joints capable of detecting the failure behaviours of rock I/II/III mixed mode fractures under creep loading. Uniaxial compression and multistage creep tests are performed on prefabricated sandstone specimens with intersecting joints of 0°/0°, 0°/30°, 0°/60°, and 0°/90°. The experimental results show that with the increase in the number of prefabricated intersecting joints, the uniaxial compressive strength and elastic modulus values of the sandstone specimens gradually decrease. In addition, the sandstone specimens experience relatively few AE events and minor axial strain variations in the first creep stage and the second creep stage of the multistage creep test. The axial strain increases sharply due to the sharp increase in the number of AE events in the third creep stage. The 0°/60° sandstone specimen undergoes accelerated creep failure, resulting in mixed X-shaped tensile‒shear rupture. The RA value is high based on the quantification of the creeping cracks using the acoustic emission parameters of the rise angle (RA) and average frequency (AF). The AF values of the 0°/0°, 0°/30°, and 0°/90° sandstone specimens are high. The experimental results show that a larger joint intersection angle leads to greater mutual restraints and greater effects of prefabricated crack propagation in the rock specimens, thus increasing the final failure strength. Finally, based on the acoustic emission count, a characteristic variable D suitable for characterizing the creep damage evolution of a joint rock mass is established. The findings of this paper can facilitate an effective understanding of the creep effect of I/II/III mixed mode fracture and its micromechanism. The research results will have a certain reference value for the detection and risk mitigation of instantaneous and time-delayed rockbursts.

Efficacy and safety of EGFR-TKI combined with WBRT vs. WBRT alone in the treatment of brain metastases from NSCLC: a systematic review and meta-analysis.

Background: The efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain metastases in non-small cell lung cancer patients remains to be determined. Methods: A systematic search was conducted using databases including PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI), aiming to identify relevant clinical studies on the treatment of brain metastases originating from non-small cell lung cancer through the combination of EGFR-TKI and WBRT. Statistical analysis was performed utilizing Stata 17.0 software, covering clinical studies published until March 1, 2023. Results: This analysis incorporated 23 randomized controlled trials (RCTs), involving a total of 2,025 patients. Of these, 1,011 were allocated to the group receiving both EGFR-TKI and WBRT, while 1,014 were assigned to the WBRT alone group. The findings reveal that the combination of EGFR-TKI and WBRT significantly improves the intracranial objective remission rate (RR = 1.57, 95% CI: 1.42-1.74, p < 0.001), increases the intracranial disease control rate (RR = 1.30, 95% CI: 1.23-1.37, p < 0.001), and enhances the 1-year survival rate (RR = 1.48, 95% CI: 1.26-1.73, p < 0.001). Additionally, this combined treatment was associated with a significant survival advantage (RR = 1.48, 95% CI: 1.26-1.73, p < 0.001) and a reduced incidence of adverse effects (RR = 0.65, 95% CI: 0.51-0.83, p < 0.001), particularly with respect to nausea and vomiting (RR = 0.54, 95% CI: 0.37-0.81, p = 0.002) and myelosuppression (RR = 0.59, 95% CI: 0.40-0.87, p = 0.008). However, no statistically significant differences were observed for diarrhea (RR = 1.15, 95% CI: 0.82-1.62, p = 0.418), and skin rash (RR = 1.35, 95% CI: 0.88-2.07, p = 0.164). Conclusion: In contrast to WBRT alone, the combination of EGFR-TKI and WBRT significantly improves intracranial response, enhancing the objective response rate, disease control rate, and 1-year survival rate in NSCLC patients with brain metastases. Moreover, aside from mild cases of rash and diarrhea, there is no statistically significant increase in the incidence of additional adverse effects. Based on the comprehensive evidence collected, the use of third-generation EGFR-TKI combined with WBRT is recommended as the preferred treatment for NSCLC patients with brain metastases, offering superior management of metastatic brain lesions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#, CRD42023415566.

Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov., isolated from desert soil, and reclassification of Pedobacter xinjiangensis as Desertivirga xinjiangensis comb. nov. and Pedobacter mongoliensis as Paradesertivirga mongoliensis gen.nov., comb. nov.

Two novel bacterial strains, designated as SYSU D00823T and SYSU D00873T, were isolated from sandy soil of the Gurbantunggut Desert in Xinjiang, north-west China. SYSU D00823T and SYSU D00873T shared 99.0 % 16S rRNA gene sequence identity, and were both most closely related to Pedobacter xinjiangensis 12157T with 96.1 % and 96.0 % similarities, respectively. Phylogenetic and phylogenomic analyses revealed that the two isolates and P. xinjiangensis 12157T formed a separate distinct cluster in a stable subclade with the nearby species Pedobacter mongoliensis 1-32T, as well as the genera Pararcticibacter and Arcticibacter. Furthermore, P. mongoliensis 1-32T formed a separate deep-branching lineage and did not form a cluster with members of the genus Pedobacter. The average nucleotide identity and digital DNA-DNA hybridization values between SYSU D00823T and SYSU D00873T and related species were well below the thresholds for species delineation (<81.0 % and <24.0 %, respectively). The genomes of SYSU D00823T and SYSU D00873T were 6.19 and 6.43 Mbp in size with 40.4 % and 40.5 % DNA G+C contents, respectively. The predominant fatty acids (>10 %) of SYSU D00823T and SYSU D00873T were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). Menaquinone-7 was the only respiratory quinone. The major polar lipids were phosphatidylethanolamine, glycosphingolipid, aminoglycolipid/glycolipid, aminophospholipid and three or four unidentified polar lipids. These data indicated that strains SYSU D00823T and SYSU D00873T should be assigned to two novel species of a new genus within the family Sphingobacteriaceae, for which the names Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov. are proposed. The type strains are SYSU D00823T (=CGMCC 1.18630T=MCCC 1K04973T=KCTC 82278T) and SYSU D00873T (=CGMCC 1.18629T=MCCC 1K04974T=KCTC 82281T), respectively. Accordingly, the reclassification of P. xinjiangensis as Desertivirga xinjiangensis comb. nov., and P. mongoliensis as Paradesertivirga mongoliensis gen. nov., comb. nov. are also proposed.

Single-cell and bulk RNA-sequence identified fibroblasts signature and CD8+ T-cell - fibroblast subtype predicting prognosis and immune therapeutic response of bladder cancer, based on machine-learning bioinformatics retrospective study.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are found in primary and advanced tumours. They are primarily involved in tumour progression through complex mechanisms with other types of cells in the tumour microenvironment. However, essential fibroblasts-related genes (FRG) in bladder cancer still need to be explored, and there is a shortage of an ideal predictive model or molecular subtype for the progression and immune therapeutic assessment for bladder cancer, especially muscular-invasive bladder cancer based on the FRG. MATERIALS AND METHODS: CAF-related genes of bladder cancer were identified by analyzing single-cell RNA sequence datasets, and bulk transcriptome datasets and gene signatures were used to characterize them. Then, ten types of machine learning algorithms were utilized to determine the hallmark FRG and construct the FRG index (FRGI) and subtypes. Further molecular subtypes combined with CD8+ T-cells were established to predict the prognosis and immune therapy response. RESULTS: 54 BLCA-related FRG were screened by large-scale scRNA-sequence datasets. The machine learning algorithm established a 3-genes FRG index (FRGI). High FRGI represented a worse outcome. Then, FRGI combined clinical variables to construct a nomogram, which shows high predictive performance for the prognosis of bladder cancer. Furthermore, the BLCA datasets were separated into two subtypes - fibroblast hot and cold types. In five independent BLCA cohorts, the fibroblast hot type showed worse outcomes than the cold type. Multiple cancer-related hallmark pathways are distinctively enriched in these two types. In addition, high FRGI or fibroblast hot type shows a worse immune therapeutic response. Then, four subtypes called CD8-FRG subtypes were established under the combination of FRG signature and activity of CD8+ T-cells, which turned out to be effective in predicting the prognosis and immune therapeutic response of bladder cancer in multiple independent datasets. Pathway enrichment analysis, multiple gene signatures, and epigenetic alteration characterize the CD8-FRG subtypes and provide a potential combination strategy method against bladder cancer. CONCLUSIONS: In summary, we established a novel FRGI and CD8-FRG subtype by large-scale datasets and organized analyses, which could accurately predict clinical outcomes and immune therapeutic response of BLCA after surgery.

Highly Efficient and Scalable p-i-n Perovskite Solar Cells Enabled by Poly-metallocene Interfaces.

Inverted p-i-n perovskite solar cells (PSCs) are easy to process but need improved interface characteristics with reduced energy loss to prevent efficiency drops when increasing the active photovoltaic area. Here, we report a series of poly ferrocenyl molecules that can modulate the perovskite surface enabling the construction of small- and large-area PSCs. We found that the perovskite-ferrocenyl interaction forms a hybrid complex with enhanced surface coordination strength and activated electronic states, leading to lower interfacial nonradiative recombination and charge transport resistance losses. The resulting PSCs achieve an enhanced efficiency of up to 26.08% for small-area devices and 24.51% for large-area devices (1.0208 cm2). Moreover, the large-area PSCs maintain >92% of the initial efficiency after 2000 h of continuous operation at the maximum power point under 1-sun illumination and 65 °C.

Development of erythrina-based PARP-1/FTase dual-target inhibitors against lung cancer epithelial-mesenchymal transition (EMT) in vivo and in vitro.

A novel series of erythrina derivatives as PARP-1/FTase inhibitors were synthesized, and evaluated for their biological activities. Compound T9 had excellent inhibitory effects on cell viability (A549: IC50 = 1.74 µM; A549/5-Fu: IC50 = 1.03 µM) and in vitro enzyme activities (PARP-1: IC50 = 0.40 µM; FTase: IC50 = 0.067 µM). Molecular docking and point mutation assays demonstrated the interaction of compound T9 with key amino acid residues. The compound T9 exhibited potent anti-proliferation and anti-migration capabilities against A549 and A549/5-Fu cells. PCR array and western blot results showed that compound T9 could effectively inhibit EMT-related proteins in A549 and A549/5-Fu cells, thereby inhibiting the development of lung cancer. Importantly, compound T9 could significantly inhibit tumor growth in the A549 xenograft tumor model (TGI = 65.3 %). In conclusion, this study was the first presentation of the concept of dual-target inhibitors of the PARP-1/FTase enzymes. It also provides the basis for further research and development of novel PARP-1/FTase inhibitors.

Potential of FGF21 in type 2 diabetes mellitus treatment based on untargeted metabolomics.

Fibroblast growth factor 21 (FGF21) has promise for treating diabetes and its associated comorbidities. It has been found to reduce blood glucose in mice and humans; however, its underlying mechanism is not known. Here, the metabolic function of FGF21 in diabetes was investigated. Diabetic db/db mice received intraperitoneal injections of FGF21 for 28 days, the serum of each mouse was collected, and their metabolites were analyzed by untargeted metabolomics using UHPLC-MS/MS. It was found that FGF21 reduced blood glucose and oral glucose tolerance without causing hypoglycemia. Moreover, administration of FGF21 reduced the levels of TG and LDL levels while increasing those of HDL and adiponectin. Importantly, the levels of 45 metabolites, including amino acids and lipids, were significantly altered, suggesting their potential as biomarkers. We speculated that FGF21 may treat T2DM through the regulation of fatty acid biosynthesis, the TCA cycle, and vitamin digestion and absorption. These findings provide insight into the mechanism of FGF21 in diabetes and suggest its potential for treating diabetes.

High spin axion insulator.

Axion insulators possess a quantized axion field θ = π protected by combined lattice and time-reversal symmetry, holding great potential for device applications in layertronics and quantum computing. Here, we propose a high-spin axion insulator (HSAI) defined in large spin-s representation, which maintains the same inherent symmetry but possesses a notable axion field θ = (s + 1/2)2π. Such distinct axion field is confirmed independently by the direct calculation of the axion term using hybrid Wannier functions, layer-resolved Chern numbers, as well as the topological magneto-electric effect. We show that the guaranteed gapless quasi-particle excitation is absent at the boundary of the HSAI despite its integer surface Chern number, hinting an unusual quantum anomaly violating the conventional bulk-boundary correspondence. Furthermore, we ascertain that the axion field θ can be precisely tuned through an external magnetic field, enabling the manipulation of bonded transport properties. The HSAI proposed here can be experimentally verified in ultra-cold atoms by the quantized non-reciprocal conductance or topological magnetoelectric response. Our work enriches the understanding of axion insulators in condensed matter physics, paving the way for future device applications.

Restoring colistin sensitivity in colistin-resistant Salmonella and Escherichia coli: combinatorial use of berberine and EDTA with colistin.

The appearance and prevalence of multidrug-resistance (MDR) Gram-negative bacteria (GNB) have limited our antibiotic capacity to control bacterial infections. The clinical efficacy of colistin (COL), considered as the "last resort" for treating GNB infections, has been severely hindered by its increased use as well as the emergence and prevalence of mobile colistin resistance (MCR)-mediated acquired drug resistance. Identifying promising compounds to restore antibiotic activity is becoming an effective strategy to alleviate the crisis of increasing MDR. We first demonstrated that the combination of berberine (BBR) and EDTA substantially restored COL sensitivity against COL-resistant Salmonella and Escherichia coli. Molecular docking indicated that BBR can interact with MCR-1 and the efflux pump system AcrAB-TolC, and BBR combined with EDTA downregulated the expression level of mcr-1 and tolC. Mechanically, BBR combined with EDTA could increase bacterial membrane damage, inhibit the function of multidrug efflux pump, and promote oxidative damage, thereby boosting the action of COL. In addition, transcriptome analysis found that the combination of BBR and EDTA can accelerate the tricarboxylic acid cycle, inhibit cationic antimicrobial peptide (CAMP) resistance, and attenuate Salmonella virulence. Notably, the combination of BBR and EDTA with COL significantly reduced the bacterial load in the liver and spleen of a mice model infected with Salmonella. Our findings revealed that BBR and EDTA can be used as adjuvants collectively with COL to synergistically reverse the COL resistance of bacteria. IMPORTANCE: Colistin is last-resort antibiotic used to treat serious clinical infections caused by MDR bacterial pathogens. The recent emergence of transferable plasmid-mediated COL resistance gene mcr-1 has raised the specter of a rapid worldwide spread of COL resistance. Coupled with the fact of barren antibiotic development pipeline nowadays, a critical approach is to revitalize existing antibiotics using antibiotic adjuvants. Our research showed that berberine combined with EDTA effectively reversed COL resistance both in vivo and in vitro through multiple modes of action. The discovery of berberine in combination with EDTA as a new and safe COL adjuvant provides a therapeutic regimen for combating Gram-negative bacteria infections. Our findings provide a potential therapeutic option using existing antibiotics in combination with antibiotic adjuvants and address the prevalent infections caused by MDR Gram-negative pathogens worldwide.

Novel phenanthrene/bibenzyl trimers from the tubers of Bletilla striata attenuate neuroinflammation via inhibition of NF-κB signaling pathway.

Five novel (9,10-dihydro) phenanthrene and bibenzyl trimers, as well as two previously identified biphenanthrenes and bibenzyls, were isolated from the tubers of Bletilla striata. Their structures were elucidated through comprehensive analyses of NMR and HRESIMS spectroscopic data. The absolute configurations of these compounds were determined by calculating rotational energy barriers and comparison of experimental and calculated ECD curves. Compounds 5b and 6 exhibited inhibitory effects on LPS-induced NO production in BV-2 cells, with IC50 values of 12.59 ± 0.40 and 15.59 ± 0.83 µmol·L-1, respectively. A mechanistic study suggested that these compounds may attenuate neuroinflammation by reducing the activation of the AKT/IκB/NF-κB signaling pathway. Additionally, compounds 3a, 6, and 7 demonstrated significant PTP1B inhibitory activities, with IC50 values of 1.52 ± 0.34, 1.39 ± 0.11, and 1.78 ± 0.01 µmol·L-1, respectively. Further investigation revealed that compound 3a might inhibit LPS-induced PTP1B overexpression and NF-κB activation, thereby mitigating the neuroinflammatory response in BV-2 cells.