The miR156 juvenility factor and PLETHORA 2 form a regulatory network and influence timing of meristem growth and lateral root emergence.

Plants develop throughout their lives: seeds become seedlings that mature and form fruits and seeds. Although the underlying mechanisms that drive these developmental phase transitions have been well elucidated for shoots, the extent to which they affect the root is less clear. However, root anatomy does change as some plants mature; meristems enlarge and radial thickening occurs. Here, in Arabidopsis thaliana, we show that overexpressing miR156A, a gene that promotes the juvenile phase, increased the density of the root system, even in grafted plants in which only the rootstock had the overexpression genotype. In the root, overexpression of miR156A resulted in lower levels of PLETHORA 2, a protein that affects formation of the meristem and elongation zone. Crossing in an extra copy of PLETHORA 2 partially rescued the effects of miR156A overexpression on traits affecting root architecture, including meristem length and the rate of lateral root emergence. Consistent with this, PLETHORA 2 also inhibited the root-tip expression of another miR156 gene, miR156C. We conclude that the system driving phase change in the shoot affects developmental progression in the root, and that PLETHORA 2 participates in this network.

Dynamic viral integration patterns actively participate in the progression of BK polyomavirus-associated diseases after renal transplantation.

The classical lytic infection theory along with large T antigen-mediated oncogenesis cannot explain the BK polyomavirus (BKPyV)-associated tumor secondary to BKPyV-associated nephropathy (BKVAN), viremia/DNAemia, and viruria after renal transplantation. This study performed virome capture sequencing and pathological examination on regularly collected urine sediment and peripheral blood samples, and BKVAN and tumor biopsy tissues of 20 patients with BKPyV-associated diseases of different stages. In the early noncancerous stages, well-amplified integration sites were visualized by in situ polymerase chain reaction, simultaneously with BKPyV inclusion bodies and capsid protein expression. The integration intensity, the proportion of microhomology-mediated end-joining integration, and host PARP-1 and POLQ gene expression levels increased with disease progression. Furthermore, multiomics analysis was performed on BKPyV-associated urothelial carcinoma tissues, identifying tandem-like structures of BKPyV integration using long-read genome sequencing. The carcinogenicity of BKPyV integration was proven to disturb host gene expression and increase viral oncoprotein expression. Fallible DNA double-strand break repair pathways were significantly activated in the parenchyma of BKPyV-associated tumors. Olaparib showed an antitumor activity dose-response effect in the tumor organoids without BRCA1/2 genes mutation. In conclusion, the dynamic viral integration patterns actively participate in the progression of BKPyV-associated diseases and thus could be a potential target for disease monitoring and intervention.

Clinical features of Talaromyces marneffei infection in HIV-positive and HIV-negative individuals: A retrospective study in southern China.

Talaromyces marneffei (TSM) is a temperature-dependent dimorphic fungus endemic to Southeast Asia and southern China. As the number of people at risk of TSM infection continues to increase, the clinical manifestations are becoming increasingly complex, posing challenges for clinical management. In this study, we analyzed the medical records of 99 patients (71 human immunodeficiency virus [HIV]-positive and 28 HIV-negative) diagnosed with TSM infection from January 1, 2017, to December 31, 2022, in southern China and compared the clinical manifestations in HIV-positive and HIV-negative patients. Most patients (83/99, 84%) were male. The incidence of skin and soft tissue involvement (48% vs. 21%, P = .016); disseminated infection with blood circulation, hematopoietic, lymphatic, alimentary, or central nervous system involvement (69% vs. 36%, P = .002); and gastrointestinal bleeding (33% vs. 9%, P = .023) was higher in the HIV-positive group than the HIV-negative group. The HIV-positive group also had significantly higher alanine aminotransferase (ALT) levels (31 [26-42] vs. 14 [11-16] U/l, P < .001) and ALT/aspartate transaminase ratio (1.9 [1.5-2.2] vs. 1.3 [1.1-1.6], P = .006) than the HIV-negative group. The time to diagnosis (5.5 ± 1.1 vs. 5.1 ± 1.4 days, P = .103), antifungal regimen (P = .278), case fatality rate (20% vs. 21%, P = .849), and relapse/reinfection rate (11% vs. 19%, P = .576) did not differ significantly between the HIV-positive and HIV-negative groups. Poor antiretroviral therapy adherence (OR = 26.19, 95%CI 3.26-210.70, P = .002), advanced age (OR = 1.13, 95%CI 1.03-1.23, P = .010), and Epstein-Barr virus co-infection (OR = 37.13, 95%CI 3.03-455.64, P = .005) were independent risk factors for all-cause mortality from TSM infection in HIV-positive patients. Overall, the predominant infection sites, clinical manifestations, and complications of TSM infection differed by HIV status. However, with prompt diagnosis and appropriate treatment, HIV-positive patients with TSM infection can have similar outcomes to HIV-negative patients.

There are certain differences in the clinical features, sites of infection, and associated complications of Talaromyces marneffei infection between individuals with and without human immunodeficiency virus. It is necessary to accurately identify individuals at high risk to enable prompt diagnosis and standardized treatment.

Fatal BK polyomavirus-associated pneumonia: report of two cases with literature review.

BACKGROUND: In immunocompromised populations, such as patients with AIDS and recipients of solid organ and hematopoietic stem cell transplants, BK polyomavirus (BKPyV) can reactivate and cause several diseases, which can lead to death in their severe forms. Unlike hemorrhagic cystitis and BKPyV-associated nephropathy, BKPyV-associated pneumonia is rare, with only seven known cases worldwide. However, the disease can rapidly progress with extremely high mortality. CASE PRESENTATION: Herein, we report two cases of BKPyV-associated pneumonia following hematopoietic stem cell transplantation. Both patients had consistent infectious pneumonia and graft-versus-host disease after stem cell transplantation. The diagnosis of BKPyV-associated pneumonia was confirmed by metagenomic next-generation sequencing and polymerase chain reaction after the sudden worsening of the pulmonary infection signs and symptoms concomitant with renal dysfunction and systemic immune weakening. Both patients eventually died of systemic multi-organ failure caused by severe pneumonia. CONCLUSIONS: Currently, BKPyV reactivation cannot be effectively prevented. Immunocompromised patients must actively manage their primary lung infections, pay close attention to pulmonary signs and imaging changes. Especially during and after steroid pulse therapy or immunosuppressive therapy for graft versus host diseases, BKPyV load in blood/urine needs to be regularly measured, and the immunosuppressive intensity should be adjusted properly after the BKPyV reactivation diagnosis. Clinical trials of new antiviral drugs and therapies for BKPyV are urgently needed.

Manifold-based respiratory phase estimation enables motion and distortion correction of free-breathing cardiac diffusion tensor MRI.

PURPOSE: For in vivo cardiac DTI, breathing motion and B0 field inhomogeneities produce misalignment and geometric distortion in diffusion-weighted (DW) images acquired with conventional single-shot EPI. We propose using a dimensionality reduction method to retrospectively estimate the respiratory phase of DW images and facilitate both distortion correction (DisCo) and motion compensation. METHODS: Free-breathing electrocardiogram-triggered whole left-ventricular cardiac DTI using a second-order motion-compensated spin echo EPI sequence and alternating directionality of phase encoding blips was performed on 11 healthy volunteers. The respiratory phase of each DW image was estimated after projecting the DW images into a 2D space with Laplacian eigenmaps. DisCo and motion compensation were applied to the respiratory sorted DW images. The results were compared against conventional breath-held T2 half-Fourier single shot turbo spin echo. Cardiac DTI parameters including fractional anisotropy, mean diffusivity, and helix angle transmurality were compared with and without DisCo. RESULTS: The left-ventricular geometries after DisCo and motion compensation resulted in significantly improved alignment of DW images with T2 reference. DisCo reduced the distance between the left-ventricular contours by 13.2% ± 19.2%, P < .05 (2.0 ± 0.4 for DisCo and 2.4 ± 0.5 mm for uncorrected). DisCo DTI parameter maps yielded no significant differences (mean diffusivity: 1.55 ± 0.13 × 10-3 mm2 /s and 1.53 ± 0.13 × 10-3 mm2 /s, P = .09; fractional anisotropy: 0.375 ± 0.041 and 0.379 ± 0.045, P = .11; helix angle transmurality: 1.00% ± 0.10°/% and 0.99% ± 0.12°/%, P = .44), although the orientation of individual tensors differed. CONCLUSION: Retrospective respiratory phase estimation with LE-based DisCo and motion compensation in free-breathing cardiac DTI resulting in significantly reduced geometric distortion and improved alignment within and across slices.

Aerobic Copper-Catalyzed Four-Component Reaction of O-Phenylenediamines, Isocyanides, and Selenium Powder for the Assembly of Benzo[4,5]imidazo[2,1-c][1,2,4]selenadiazol-3-imine Derivatives.

A convenient, four-component reaction of o-phenylenediamines, isocyanides, and selenium powder catalyzed by a natural abundant copper/air (O2) catalyst system has been developed, providing a highly step and atom economical protocol for the synthesis of benzo[4,5]imidazo[2,1-c][1,2,4]selenadiazol-3-imine derivatives with excellent yields and good functional group tolerance. This method enables the construction of an imidazo[2,1-c][1,2,4]selenadiazol ring, one N-Se bond, one C-Se bond, and three C-N bonds in a single step with only water as the byproduct. Preliminary mechanistic studies imply that the copper/air (O2)-catalyzed cyclization proceeds via a selenium-centered radical intermediate.

Structure of a prokaryotic virtual proton pump at 3.2 A resolution.

To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump' in the inner membrane, called AdiC, that imports L-arginine from the gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis, facilitation of insulin release from pancreatic beta-cells, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 A resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.

Nuclear transport receptor KA120 regulates molecular condensation of MAC3 to coordinate plant immune activation.

The nucleocytoplasmic exchange is of fundamental importance to eukaryotic life and is mediated by karyopherins, a superfamily of nuclear transport receptors. However, the function and cargo spectrum of plant karyopherins are largely obscure. Here, we report proximity-labeling-based proteomic profiling of in vivo substrates of KA120, a karyopherin-ß required for suppressing autoimmune induction in Arabidopsis. We identify multiple components of the MOS4-associated complex (MAC), a conserved splicing regulatory protein complex. Surprisingly, we find that KA120 does not affect the nucleocytoplasmic distribution of MAC proteins but rather prevents their protein condensation in the nucleus. Furthermore, we demonstrate that MAC condensation is robustly induced by pathogen infection, which is sufficient to activate defense gene expression, possibly by sequestrating negative immune regulators via phase transition. Our study reveals a noncanonical chaperoning activity of a plant karyopherin, which modulates the nuclear condensation of an evolutionarily conserved splicing regulatory complex to coordinate plant immune activation.

Inhibition of BRD4 expression attenuates the inflammatory response and apoptosis by downregulating the HMGB-1/NF-κB signaling pathway following traumatic brain injury in rats.

Neuroinflammation plays an important part in secondary traumatic brain injury (TBI). Bromodomain-4 (BRD4) exerts specific proinflammatory effects in various neuropathological conditions. However, the underlying mechanism of action of BRD4 after TBI is not known. We measured BRD4 expression after TBI and investigated its possible mechanism of action. We established a model of craniocerebral injury in rats. After different intervention measures, we used western blotting, immunofluorescence, real-time reverse transcription-quantitative polymerase chain reaction, neuronal apoptosis, and behavioral tests to evaluate the effect of BRD4 on brain injury. At 72 h after brain injury, BRD4 overexpression aggravated the neuroinflammatory response, neuronal apoptosis, neurological dysfunction, and blood-brain-barrier damage, whereas upregulating expression of HMGB-1 and NF-κB had the opposite effect. Glycyrrhizic acid could reverse the proinflammatory effect of BRD4 overexpression upon TBI. Our results suggest that: (i) BRD4 may have a proinflammatory role in secondary brain injury through the HMGB-1/NF-κB signaling pathway; (ii) inhibition of BRD4 expression may play a part in secondary brain injury. BRD4 could be targeted therapy strategy for brain injury.

USP11 exacerbates neuronal apoptosis after traumatic brain injury via PKM2-mediated PI3K/AKT signaling pathway.

Ubiquitin-specific protease 11 (USP11) is a ubiquitin-specific protease involved in the regulation of protein ubiquitination. However, its role in traumatic brain injury (TBI) remains unclear. This experiment suggests that USP11 is possibly involved in regulating neuronal apoptosis in TBI. Therefore, we use precision impactor device to established a TBI rat model and assayed the role of USP11 by overexpressing and inhibiting USP11. We found that Usp11 expression increased after TBI. In addition, we hypothesized that pyruvate kinase M2 (PKM2) is a potential USP11 target and experimentally confirmed that upregulation of Usp11 increased Pkm2 expression. Furthermore, elevated USP11 levels exacerbate blood-brain barrier damage, brain edema, and neurobehavioral impairment and cause apoptosis induction through Pkm2 upregulation. Moreover, we hypothesize that PKM2-induced neuronal apoptosis is mediated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Our findings were confirmed by changes in Pi3k and Akt expression with Usp11 upregulation and downregulation and PKM2 inhibition. In conclusion, our findings show that USP11 exacerbates injury in TBI through PKM2 and causes neurological impairment and neuronal apoptosis through the PI3K/AKT signaling pathway.

Corrigendum: Dynamic risk prediction of BK polyomavirus reactivation after renal transplantation.

[This corrects the article DOI: 10.3389/fimmu.2022.971531.].

Sided functions of an arginine-agmatine antiporter oriented in liposomes.

The arginine-dependent extreme acid resistance system helps enteric bacteria survive the harsh gastric environment. At the center of this multiprotein system is an arginine-agmatine antiporter, AdiC. To maintain cytoplasmic pH, AdiC imports arginine and exports its decarboxylated product, agmatine, resulting in a net extrusion of one "virtual proton" in each turnover. The random orientation of AdiC in reconstituted liposomes throws up an obstacle to quantifying its transport mechanism. To overcome this problem, we introduced a mutation, S26C, near the substrate-binding site. This mutant exhibits substrate recognition and pH-dependent activity similar to those of the wild-type protein but loses function completely upon reaction with thiol reagents. The membrane-impermeant MTSES reagent can then be used as a cleanly sided inhibitor to silence those S26C-AdiC proteins whose extracellular portion projects from the external side of the liposome. Alternatively, the membrane-permeant MTSEA and membrane-impermeant reducing reagent, TCEP, can be used together to inhibit proteins in the opposite orientation. This approach allows steady-state kinetic analysis of AdiC in a sided fashion. Arginine and agmatine have similar Michaelis-Menten parameters for both sides of the protein, while the extracellular side selects arginine over argininamide, a mimic of the carboxylate-protonated form of arginine, more effectively than does the cytoplasmic side. Moreover, the two sides of AdiC have different pH sensitivities. AdiC activity increases to a plateau at pH 4 as the extracellular side is acidified, while the cytoplasmic side shows an optimal pH of 5.5, with further acidification inhibiting transport. This oriented system allows more precise analysis of AdiC-mediated substrate transport than has been previously available and permits comparison to the situation experienced by the bacterial membrane under acid stress.

Incidence and Risk Factors for Hypoxia in Deep Sedation of Propofol for Artificial Abortion Patients.

Background: Respiratory depression is a life-threatening adverse effect of deep sedation. This study aimed to investigate the factors related to hypoxia caused by propofol during intravenous anesthesia. Methods: Three hundred and eight patients who underwent painless artificial abortion in the outpatient department of Shanghai Tenth People's Hospital between November 1, 2019 and June 30, 2020 were divided into two groups according to whether the patients experienced hypoxia (SpO2 < 95%). Preoperative anxiety assessments, anesthesia process, and operation-related information of the two groups were analyzed. The univariate analysis results were further incorporated into logistic regression analysis for multivariate analysis to determine the independent risk factors affecting hypoxia. Results: Univariate analysis revealed that body mass index (BMI) (21.80 ± 2.94 vs. 21.01 ± 2.39; P = 0.038, 95% confidence interval (CI) = [-1.54, -0.04]), propofol dose (15.83 ± 3.21 vs. 14.39 ± 3.01; P = 0.002, CI = [-2.34, -0.53]), menopausal days (49.64 ± 6.03 vs. 52.14 ± 5.73; P = 0.004, CI = [0.79, 4.21]), State Anxiety Inventory score (51.19 ± 7.55 vs. 44.49 ± 8.96; P < 0.001, CI = [-9.26, -4.15]), and Self-rating Anxiety Scale score (45.86 ± 9.48 vs. 42.45 ± 9.88; P = 0.021, CI = [-6.30, -0.53]) were statistically significant risk factors for hypoxia during the operation. Logistic regression analysis showed that propofol dosage, menopausal days, and State Anxiety Inventory score were independent risk factors for hypoxia. Conclusion: Patient anxiety affects the incidence of hypoxia when undergoing deep intravenous anesthesia with propofol. We can further speculate that alleviating patient anxiety can reduce the incidence of hypoxia. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR2000032167].

The Effect of Relaxation Therapy on Hypoxia During Intravenous Propofol Anesthesia in Patients With Pre-operative Anxiety: A Prospective Randomized Controlled Trial.

Background: This study aimed to investigate the effect of relaxation therapy on hypoxia during intravenous propofol anesthesia in patients with pre-operative anxiety. Methods: Two-hundred and eighty patients were randomly categorized in the experimental group (relaxation therapy group) and control group. The Spielberger State-Trait Anxiety Inventory (S-STAI) was administered 30 to 60 min pre-operatively to assess the patient's current anxiety status and select appropriate patients. Patients in the experimental group received pre-surgical relaxation therapy. Decrease in oxygen saturation during the procedure was recorded for each patient group, and the relevant data were compared between the two groups. Results: The basic S-STAI scores of the experimental and control groups were 56.88 ± 2.91 and 57.27 ± 3.56, respectively (p = 0.331). The difference was not statistically significant. The incidence of hypoxia in the experimental group during painless artificial abortion [routine blood oxygen saturation (SpO2) <95%, duration >15 s] decreased from 30 to 12.3%. Conclusion: Relaxation therapy may effectively reduce the incidence of hypoxia during painless artificial abortion by using less dose of propofol. It may help patients relieve their anxiety and improve perioperative safety. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2000032109).

Serum Soluble ST2 Is a Valuable Prognostic Biomarker in Patients With Acute Heart Failure.

BACKGROUND: This study aimed to investigate the clinical utility of different soluble suppression of tumorigenicity 2 (sST2) levels in assessing the severity and prognosis of patients with acute heart failure (AHF). METHODS: This was a prospective cohort study. Three hundred and thirty-one consecutively enrolled AHF patients from March 2018 to November 2019 were divided into 3 subgroups according to sST2 levels: T1 (1.15-7.70 ng/ml; N = 110), T2 (7.71-17.24 ng/ml; N = 111), and T3 (17.26-47.42 ng/ml; N = 110). The patients were followed up for a median period of 21.0 months for the development of the primary endpoint. Cox proportional hazards model was performed to evaluate the prognostic value of sST2 for the clinical outcomes. RESULTS: The mean age of patients was 69 years (range, 34-93 years), and 70.4% were male. During the follow-up period, 63 participants died. Patients with higher sST2 levels had lower left ventricular ejection fraction (correlation = -0.119, P = 0.031), and higher New York Heart Association classification (correlation = 0.443, P < 0.001) and N-terminal pro-B type natriuretic peptide (NT-proBNP) levels (correlation = 0.392, P < 0.001). Higher sST2 was also associated with creatinine, urea nitrogen, hemoglobin, and left ventricular mass index. Multivariate analysis revealed that sST2 (per log unit, hazard ratio: 2.174, 95% confidence interval [CI] 1.012-4.67, P = 0.047) and NT-proBNP (per log unit, HR 2.171, 95%CI 1.169-4.032, P < 0.001) were independent risk factors for the primary outcome in all patients with AHF. CONCLUSION: sST2 can provide prognostic information in AHF. The higher the sST2 level in patients with AHF, the higher the incidence of cardiovascular death.

Urolithin B suppressed osteoclast activation and reduced bone loss of osteoporosis via inhibiting ERK/NF-κB pathway.

OBJECTIVES: The main target of current drugs for alleviating bone loss is osteoclasts. However, the long-term application of such drugs will also cause side effects. Therefore, it is of great need to develop new and safer therapeutics for osteoporosis. In recent years, drug development based on gut microbiota has gradually attracted attention. This manuscript investigates the inhibitory effect of urolithin B (UB) on osteoclastogenesis and differentiation in vitro and in ovariectomized (OVX) mice. MATERIALS AND METHODS: CCK-8 was used to analyse the cytotoxicity of UB; BMMs cells were differentiated into osteoclasts by RANKL, and respectively treated with 1, 5, and 25 µmol/L UB during this process. After one week of intervention, tartrate-resistant acid phosphatase (TRAP) staining was used to analyse the number and average area of osteoclasts. F-actin staining and immunofluorescence staining were conducted to evaluate the morphology and function of osteoclasts. Bone resorption function of osteoclasts was detected by Pit Formation Assay. The expression of osteoclast-related protein genes in RAW264.7 cells were investigated via western blot and RT-PCR assays. Western blot analysis of RANKL-mediated activation of MAPK/NF-κB pathway after 0, 5, 15, 30, 60 min of intervention. For in vivo experiments, OVX mice received intraperitoneal injection of 10, 50 mg/kg every two days, 8 weeks later, the femurs of mice were taken for morphological analysis, and the serum content of CTX-1, a bone metabolism index, was analysed. RESULTS: UB could inhibit the osteoclast differentiation of rankl-induced bone marrow macrophages (BMMs) and RAW264.7 cells in vitro, suppress the uptake activity of hydroxyapatite and expression of osteoclast-related gene MMP9, CTSK, NFATc1 and c-fos. Furthermore, UB repressed the rankl-induced phosphorylation and degradation of IκB and the phosphorylation of P65 in the NF-κB pathway of RAW264.7 cells, and also down-regulated the phosphorylation level of ERK in the MAPK pathway. For in vivo studies, UB-treated OVX mice showed more significant improved various parameters of distal femur compared with the control group, with fewer NFATc1, MMP9 and TRAP-positive osteoclasts in bone tissues, and less serum content of CTX-1. CONCLUSION: Urolithin B attenuated bone loss in OVX mice by inhibiting the formation and activation of osteoclasts via down-regulation of the ERK/NF-κB signalling pathway.

Dynamic risk prediction of BK polyomavirus reactivation after renal transplantation.

Purpose: To construct a dynamic prediction model for BK polyomavirus (BKV) reactivation during the early period after renal transplantation and to provide a statistical basis for the identification of and intervention for high-risk populations. Methods: A retrospective study of 312 first renal allograft recipients with strictly punctual follow-ups was conducted between January 2015 and March 2022. The covariates were screened using univariable time-dependent Cox regression, and those with P<0.1 were included in the dynamic and static analyses. We constructed a prediction model for BKV reactivation from 2.5 to 8.5 months after renal transplantation using dynamic Cox regression based on the landmarking method and evaluated its performance using the area under the curve (AUC) value and Brier score. Monte-Carlo cross-validation was done to avoid overfitting. The above evaluation and validation process were repeated in the static model (Cox regression model) to compare the performance. Two patients were presented to illustrate the application of the dynamic model. Results: We constructed a dynamic prediction model with 18 covariates that could predict the probability of BKV reactivation from 2.5 to 8.5 months after renal transplantation. Elder age, basiliximab combined with cyclophosphamide for immune induction, acute graft rejection, higher body mass index, estimated glomerular filtration rate, urinary protein level, urinary leukocyte level, and blood neutrophil count were positively correlated with BKV reactivation, whereas male sex, higher serum albumin level, and platelet count served as protective factors. The AUC value and Brier score of the static model were 0.64 and 0.14, respectively, whereas those of the dynamic model were 0.79 ± 0.05 and 0.08 ± 0.01, respectively. In the cross-validation, the AUC values of the static and dynamic models decreased to 0.63 and 0.70 ± 0.03, respectively, whereas the Brier score changed to 0.11 and 0.09 ± 0.01, respectively. Conclusion: Dynamic Cox regression based on the landmarking method is effective in the assessment of the risk of BKV reactivation in the early period after renal transplantation and serves as a guide for clinical intervention.

Regulation of Plant Immunity by Nuclear Membrane-Associated Mechanisms.

Unlike animals, plants do not have specialized immune cells and lack an adaptive immune system. Instead, plant cells rely on their unique innate immune system to defend against pathogens and coordinate beneficial interactions with commensal and symbiotic microbes. One of the major convergent points for plant immune signaling is the nucleus, where transcriptome reprogramming is initiated to orchestrate defense responses. Mechanisms that regulate selective transport of nuclear signaling cargo and chromatin activity at the nuclear boundary play a pivotal role in immune activation. This review summarizes the current knowledge of how nuclear membrane-associated core protein and protein complexes, including the nuclear pore complex, nuclear transport receptors, and the nucleoskeleton participate in plant innate immune activation and pathogen resistance. We also discuss the role of their functional counterparts in regulating innate immunity in animals and highlight potential common mechanisms that contribute to nuclear membrane-centered immune regulation in higher eukaryotes.

A Comprehensive Analysis Identified Hub Genes and Associated Drugs in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly and has become a growing global health problem causing great concern. However, the pathogenesis of AD is unclear and no specific therapeutics are available to provide the sustained remission of the disease. In this study, we used comprehensive bioinformatics to determine 158 potential genes, whose expression levels changed between the entorhinal and temporal lobe cortex samples from cognitively normal individuals and patients with AD. Then, we clustered these genes in the protein-protein interaction analysis and identified six significant genes that had more biological functions. Besides, we conducted a drug-gene interaction analysis of module genes in the drug-gene interaction database and obtained 26 existing drugs that might be applied for the prevention and treatment of AD. In addition, a predictive model was built based on the selected genes using different machine learning algorithms to identify individuals with AD. These findings may provide new insights into AD therapy.