Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging.

To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging. Furthermore, we observed that IgG could induce a pro-senescent state in macrophages and microglia, thereby exacerbating tissue aging, and that targeted reduction of IgG mitigated aging across various tissues in male mice. This study provides a high-resolution spatial depiction of aging and indicates the pivotal role of immunoglobulin-associated senescence during the aging process.

Facial Amphiphile-Modified Lipids Highly Sensitize Liposomes toward Secretory Phospholipase A2.

Upregulated secretory phospholipase A2 (sPLA2) in tumors has been proposed as a stimulus to trigger drug release from liposomes for therapeutic effects. However, the current strategy for developing sPLA2-responsive liposomes merely considering substrate preference suffers from limited membrane disruptive effects induced by enzymatic hydrolysis and safety issues resulting from the overuse of sPLA2-preferred lipids. Here, a membrane-destabilizing mechanism based on enzymatic extraction and the transition of facial amphiphiles (FAs) within lipid membranes was introduced. Enzymatic degradation of FA-modified lipids, a process involving substrate extraction of lipids from membranes and cleavage of sn-2 ester bonds by sPLA2, rotation, and interface settling of detached FAs, caused tremendous efflux of payloads from liposomes, termed the SECRIS effect. In the presence of sPLA2, oxaliplatin (L-OHP) loaded liposomes containing FA-modified lipids showed enhanced drug release, comparable in vitro cytotoxicity, and excellent in vivo antitumor efficacy and reduced adverse syndromes in Colo205-bearing mice compared to conventional sPLA2-labile formulations. The discovery of the SECRIS effect creates a new pathway to engineer liposome platforms for the treatment of sPLA2-positive tumors.

Noncontact Perception of Thin-Film Transistors by the Synergy of Both Capacitive and Electrostatic Induction Mechanisms.

In recent years, the rapid expansion of research and application of the Internet of Things and wearable electronics has prompted the development of a variety of sensors to perceive physical or chemical information from both the human body and the environment, among which the proximity sensor is a kind of noncontact sensor used to detect the approach of a target and thus exhibits promising applications in human-machine interactions. Thin-film transistors are one type of key components in modern electronics and have been further developed as electrostatic-induction-type proximity sensors to perceive the approach of electrically charged objects. However, they are immune to the approach of a zero-potential object. Capacitive-induction-type proximity sensors are capable of detecting the approach of conductive targets while being less sensitive to insulated ones. Integration of both electrostatic and capacitive induction mechanisms into one proximity sensor is highly expected to broaden its perception to a variety of targets. Here, an interdigital electrode was introduced as an extended gate into an amorphous metal oxide thin-film transistor to construct proximity sensors that combine both electrostatic and capacitive induction mechanisms and therefore can sensitively perceive the approach of a variety of objects that were electrically charged, grounded, or floated. Besides proximity sensing, remote velocity measurement and positioning of an invasive object were also realized, which further extended its functions as a kind of interdigital-electrode gate transistor.

Metformin decelerates aging clock in male monkeys.

In a rigorous 40-month study, we evaluated the geroprotective effects of metformin on adult male cynomolgus monkeys, addressing a gap in primate aging research. The study encompassed a comprehensive suite of physiological, imaging, histological, and molecular evaluations, substantiating metformin's influence on delaying age-related phenotypes at the organismal level. Specifically, we leveraged pan-tissue transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to develop innovative monkey aging clocks and applied these to gauge metformin's effects on aging. The results highlighted a significant slowing of aging indicators, notably a roughly 6-year regression in brain aging. Metformin exerts a substantial neuroprotective effect, preserving brain structure and enhancing cognitive ability. The geroprotective effects on primate neurons were partially mediated by the activation of Nrf2, a transcription factor with anti-oxidative capabilities. Our research pioneers the systemic reduction of multi-dimensional biological age in primates through metformin, paving the way for advancing pharmaceutical strategies against human aging.

Response of ecological stoichiometry and homeostasis characteristic to nitrogen addition in Hippophae rhamnoides L.

Nitrogen (N) in the atmosphere frequently affects plant growth, ecological stoichiometric equilibrium, and homeostasis stability. However, the effect of N addition application on the growth of Hippophae rhamnoides seedlings remains ambiguous. We investigated the effects of N addition on the ecological stoichiometry and homeostatic characteristics of H. rhamnoides seedlings. Greenhouse cultivation experiments were conducted at five N application levels: 0 kg ha-1 yr-1(CK), 100 kg ha-1 yr-1 (N10), 200 kg ha-1 yr-1 (N20), 400 kg ha-1 yr-1 (N40), 800 kg ha-1 yr-1 (N80). The results showed that pH and available phosphorus (AP) significantly decreased with increasing N, whereas soil C:P and N:P ratios significantly increased under the N40 and N80 treatments. The leaf C:N ratio significantly decreased with increasing N, whereas the N:P ratio increased. With N addition, the C:N ratio of plant stems and roots significantly decreased, whereas the C:P and N:P ratios significantly increased. N addition was significantly correlated with the ecological stoichiometry of plant leaves and soil properties (0.38 and 0.84, respectively). Homeostasis of the organs of H. rhamnoides seedlings exhibited an absolute steady state. The C, N, and C:P ratios of the roots exhibited insensitive states under the N40 treatment. N addition significantly modified both the soil ecological stoichiometry and the stoichiometry of H. rhamnoides seedlings. However, it did not demonstrate a pronounced negative effect on the homeostasis of H. rhamnoides seedlings. This study offers new insights into the ecological adaptation process of H. rhamnoides, particularly concerning its nutrient distribution, utilization strategies, and stability.

Gadoxetic Acid-Enhanced MRI-Based Radiomic Models for Preoperative Risk Prediction and Prognostic Assessment of Proliferative HCC.

RATIONALE AND OBJECTIVES: Proliferative hepatocellular carcinoma (HCC) is associated with high invasiveness and poor prognosis. This study aimed to investigate the preoperative risk prediction and prognostic value of different radiomics models and a nomogram for proliferative HCC. MATERIALS AND METHODS: Patients were randomly divided into a training cohort (n = 156) and a validation cohort (n = 66) in a 7:3 ratio. Original and delta (the different value between imaging features extracted from two different phases) radiomics features were extracted from T1-weighted imaging (T1WI), arterial, and hepatobiliary phases to construct models using different machine learning algorithms. Logistic regression was used to select clinical independent risk factors. A nomogram was constructed by integrating the optimal radiomics model score with independent risk factors. The diagnostic efficacy and clinical utility of the models were assessed. Subsequently, patients were stratified into high-risk and low-risk subgroups based on radiomics model scores and nomogram scores, and both recurrence-free survival (RFS) and overall survival (OS) were evaluated. RESULTS: Multivariate logistic regression analysis showed that BCLC stage and combined radscore were independent predictors of proliferative HCC. The area under the curve (AUC) of the nomogram incorporating these factors was 0.838 and 0.801 in the training and validation cohorts, respectively, with good predictive performance. Multivariate Cox regression analysis shows that the delta radiomics model (DR)-predicted proliferative HCC can independently predict RFS and OS, with scores from the delta radiomics model performing best in prognostic risk stratification. CONCLUSION: The nomogram can effectively predict proliferative HCC, while different radiomics models and the nomogram can offer varying prognostic stratification values.

Piezoelectric Enhancement in P(VDF-TrFE) Copolymer Films via Controlled and Template-Induced Epitaxy.

The surge in wearable electronics and Internet of Things technologies necessitates the development of both flexible sensors and a sustainable, efficient, and compact power source. The latter further challenges conventional batteries due to environmental pollution and compatibility issues. Addressing this gap, piezoelectric energy harvesters emerge as one kind of promising alternative to convert mechanical energy from ambient sources to electrical energy to charge those low-energy-consumption electronic devices. Despite slightly lower piezoelectric performance compared with those inorganic materials, piezoelectric polymers, notably poly(vinylidene fluoride-co-trifluoroethylene) P(VDF-TrFE), offer compelling properties for both flexible mechanical energy harvesting and self-powered strain/stress sensing, though their piezoelectric performance is expected to be further enhanced via varieties of modulation strategies of microstructures. Herein, we reported the controlled epitaxy process of micrometer-thick copolymer films with the cooperation of friction-transferred poly(tetrafluoroethylene) templates and precise modulation of the annealing conditions. Epitaxial P(VDF-TrFE) films present averaged d33 piezoelectric coefficient of -58.2 pC/N between 50 Hz and 1 kHz with good electromechanical and thermal stability. Owing to the nature of anisotropic crystallization, the epitaxial films exhibit an anisotropic transverse piezoelectric property. Epitaxial films were further utilized for mechanical energy harvesting and monitoring of human pulsation and respiration. This study provided a feasible route for the development of high-performance flexible piezoelectric devices to meet the requirement of flexible electronics.

Diagnostic Model for Proliferative HCC Using LI-RADS: Assessing Therapeutic Outcomes in Hepatectomy and TKI-ICI Combination.

BACKGROUND: Proliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis. PURPOSE: To develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI-RADS) and assess its prognostic value. STUDY TYPE: Retrospective. POPULATION: 241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets. 57 HCC patients received combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). FIELD STRENGTH/SEQUENCE: 3.0 T, T1- and T2-weighted, diffusion-weighted, in- and out-phase, T1 high resolution isotropic volume excitation and dynamic gadoxetic acid-enhanced imaging. ASSESSMENT: LI-RADS v2018 and other MRI features (intratumoral artery, substantial hypoenhancing component, hepatobiliary phase peritumoral hypointensity, and irregular tumor margin) were assessed. A diagnostic model for proliferative HCC was established, stratifying patients into high- and low-risk groups. Follow-up occurred every 3-6 months, and recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS) in different groups were compared. STATISTICAL TESTS: Fisher's test or chi-square test, t-test or Mann-Whitney test, logistic regression, Harrell's concordance index (C-index), Kaplan-Meier curves, and Cox proportional hazards. Significance level: P < 0.05. RESULTS: The diagnostic model, incorporating corona enhancement, rim arterial phase hyperenhancement, infiltrative appearance, intratumoral artery, and substantial hypoenhancing component, achieved a C-index of 0.823 (training set) and 0.804 (validation set). Median follow-up was 32.5 months (interquartile range [IQR], 25.1 months) for postsurgery patients, and 16.8 months (IQR: 13.2 months) for combination-treated patients. 99 patients experienced recurrence, and 30 demonstrated tumor nonresponse. Differences were significant in RFS and OS rates between high-risk and low-risk groups post-surgery (40.3% vs. 65.8%, 62.3% vs. 90.1%, at 5 years). In combination-treated patients, PFS rates differed significantly (80.6% vs. 7.7% at 2 years). DATA CONCLUSION: The MR-based model could pre-treatment identify proliferative HCC and assist in prognosis evaluation. TECHNICAL EFFICACY: Stage 2.

Curcumin Inhibits Vasculogenic Mimicry via Regulating ETS-1 in Renal Cell Carcinoma.

BACKGROUND: Metastatic renal cell carcinoma (RCC) poses a huge challenge once it has become resistant to targeted therapy. Vasculogenic mimicry (VM) is a novel blood supply system formed by tumor cells that can circumvent molecular targeted therapies. As one of the herbal remedies, curcumin has been demonstrated to play antineoplastic effects in many different types of human cancers; however, its function and mechanism of targeting VM in RCC remains unknown. OBJECTIVE: Here, in the work, we explored the role of curcumin and its molecular mechanism in the regulation of VM formation in RCC. METHODS: RNA-sequencing analysis, immunoblotting, and immunohistochemistry were used to detect E Twenty Six-1(ETS-1), vascular endothelial Cadherin (VE-Cadherin), and matrix metallopeptidase 9 (MMP9) expressions in RCC cells and tissues. RNA sequencing was used to screen the differential expressed genes. Plasmid transfections were used to transiently knock down or overexpress ETS-1. VM formation was determined by tube formation assay and animal experiments. CD31-PAS double staining was used to label the VM channels in patients and xenograft samples. RESULTS: Our results demonstrated that VM was positively correlated with RCC grades and stages using clinical patient samples. Curcumin inhibited VM formation in dose and time-dependent manner in vitro. Using RNA-sequencing analysis, we discovered ETS-1 as a potential transcriptional factor regulating VM formation. Knocking down or overexpression of ETS-1 decreased or increased the VM formation, respectively and regulated the expression of VE-Cadherin and MMP9. Curcumin could inhibit VM formation by suppressing ETS-1, VE-Cadherin, and MMP9 expression both in vitro and in vivo. CONCLUSION: Our finding might indicate that curcumin could inhibit VM by regulating ETS-1, VE-Cadherin, and MMP9 expression in RCC cell lines. Curcumin could be considered as a potential anti-cancer compound by inhibiting VM in RCC progression.

Genome-wide CRISPR screen identifies ESPL1 limits the response of gastric cancer cells to apatinib.

Apatinib was the first anti-angiogenic agent approved for treatment of metastatic gastric cancer (GC). However, the emergence of resistance was inevitable. Thus investigating new and valuable off-target effect of apatinib directly against cancer cells is of great significance. Here, we identified extra spindle pole bodies-like 1 (ESPL1) was responsible for apatinib resistance in GC cells through CRISPR genome-wide gain-of-function screening. Loss of function studies further showed that ESPL1 inhibition suppressed cell proliferation, migration and promoted apoptosis in vitro, and accordingly ESPL1 knockdown sensitized GC cells to apatinib. In addition, we found ESPL1 interacted with mouse double minute 2 (MDM2), a E3 ubiquitin protein ligase, and the combination of MDM2 siRNA with apatinib synergistically ameliorated the resistance induced by ESPL1 overexpression. In summary, our study indicated that ESPL1 played a critical role in apatinib resistance in GC cells. Inhibition of MDM2 could rescue the sensitivity of GC cells to apatinib and reverse ESPL1-mediated resistance.

Tungsten-Doped Indium Tin Oxide Thin-Film Transistors for Dual-mode Proximity Sensing Application.

Technologies for human-machine interactions are booming now. In order to achieve multifunctional sensing abilities of electronic skins, further developments of various sensors are in urgent demand. Herein, a dual-mode proximity sensor based on an oxide thin-film transistor (TFT) is reported. Although InSnO (ITO) is featured with high mobility, the inherent high carrier concentration limits its use as a channel material for thin-film transistors. Herein, the tungsten element was introduced as a carrier suppressor to develop ITO-based semiconducting materials and devices. TFTs with amorphous tungsten-doped ITO (ITWO) channel layers were fabricated. As for a flat panel display application, the TFT device from 250 °C-annealed ITWO layer with an atomic ratio of In/Sn/W = 86:9:5 presented the optimal device performance with carrier mobility of 11.53 cm2 V-1 s-1, swing subthreshold of 0.66 V dec-1, threshold voltage of -2.18 V, and Ion/Ioff ratio of 3.33 × 107 and much small hysteresis of transfer characteristic. ITWO TFT devices were further developed as dual-mode proximity sensors that could work with both extended-gate and compact configurations, where the drain current was directly related to the surface potential of a charged object and the distance between the sensing end and the object, enabling the proximity sensing of charged stimuli. For extended-gate-configured proximity sensing, a charged object modulated the formation of a conductive channel at the semiconductor/SiO2 interface, while this conductive channel occurred at the semiconductor/air interface for compact-configured sensing. Formation of the conductive channel of the compact transistor was modulated by the electric field component in the direction perpendicular to the interface, and the drain current was sensitive to the orientation of the approaching object, which implied the capacity of angle sensing to the approach of a charged object. This work further emphasizes that the basic device performance should be optimized according to its specific application scenarios rather than only considering the requirements of the panel display.

Brown adipocyte mineralocorticoid receptor deficiency impairs metabolic regulation in diet-induced obese mice.

Activation of brown adipose tissue (BAT) contributes to energy dissipation and metabolic health. Although mineralocorticoid receptor (MR) antagonists have been demonstrated to improve metabolism under obesity, the underlying mechanisms remain incompletely understood. We aimed to evaluate the role of BAT MR in metabolic regulation. After 8 weeks of high-fat diet (HFD) feeding, BAT MR KO (BMRKO) mice manifested significantly increased bodyweight, fat mass, serum fasting glucose, and impaired glucose homeostasis compared with littermate control (LC) mice, although insulin resistance and fasting serum insulin were not significantly changed. Metabolic cage experiments showed no change in O2 consumption, CO2 production, or energy expenditure in obese BMRKO mice. RNA sequencing analysis revealed downregulation of genes related to fatty acid metabolism in BAT of BMRKO-HFD mice compared with LC-HFD mice. Moreover, H&E and immunohistochemical staining demonstrated that BMRKO exacerbated HFD-induced macrophage infiltration and proinflammatory genes in epididymal white adipose tissue (eWAT). BMRKO-HFD mice also manifested significantly increased liver weights and hepatic lipid accumulation, an increasing trend of genes related to lipogenesis and lipid uptake, and significantly decreased genes related to lipolytic and fatty acid oxidation in the liver. Finally, the level of insulin-induced AKT phosphorylation was substantially blunted in eWAT but not liver or skeletal muscle of BMRKO-HFD mice compared with LC-HFD mice. These data suggest that BAT MR is required to maintain metabolic homeostasis, likely through its regulation of fatty acid metabolism in BAT and impacts on eWAT and liver.

Discovery of a Novel Ketohexokinase Inhibitor with Improved Drug Distribution in Target Tissue for the Treatment of Fructose Metabolic Disease.

Excessive fructose absorption and its subsequent metabolisms are implicated in nonalcoholic fatty liver disease, obesity, and insulin resistance in humans. Ketohexokinase (KHK) is a primary enzyme involved in fructose metabolism via the conversion of fructose to fructose-1-phosphate. KHK inhibition might be a potential approach for the treatment of metabolic disorders. Herein, a series of novel KHK inhibitors were designed, synthesized, and evaluated. Among them, compound 14 exhibited more potent activity than PF-06835919 based on the rat KHK inhibition assay in vivo, and higher drug distribution concentration in the liver. Its good absorption, distribution, metabolism, and excretion and pharmacokinetic properties make it a promising clinical candidate.

Investigating the Role of FoxP3 in Renal Cell Carcinoma Metastasis with BAP1 or SEDT2 Mutation.

Forkhead box protein P3 (FoxP3) primarily functions as the master regulator in regulatory T cells (Tregs) differentiation, but its high level of expression has also been found in tumor cells recently. The aim of our study was to clarify the role of FoxP3 in renal cell carcinoma (RCC) progression and metastasis. We verified the FoxP3 characteristic clinicopathological data from The Cancer Genome Atlas (TCGA) database using bioinformatics tools. Meanwhile, RNA sequencing was performed to determine the FoxP3 biofunction in RCC progression. Our results showed that high expression of FoxP3 was found in BAP1- or SETD2-mutant patients with RCC, and a higher FoxP3 expression was related to worse prognosis. However, there was no statistically significant relationship between the FoxP3 IHC score and RCC malignant progression owning to the limited number of patients in our tissue microarray. Using in vitro FoxP3 loss-of-function assays, we verified that silencing FoxP3 in 786-O and ACHN cells could inhibit the cell migration/invasion capability, which was consistent with the data from RNA sequencing in 786-O cells and from the TCGA datasets. Using an in vivo nude mice orthotopic kidney cancer model, we found that silencing FoxP3 could inhibit tumor growth. In conclusion, our study demonstrated that BAP1 or SEDT2 mutation could lead to higher expression of FoxP3 in RCC patients, and FoxP3 could eventually stimulate RCC cells' invasion and metastasis, which might indicate that FoxP3 could function as a potential oncogene in RCC progression.

Clinical Characteristics of Molecularly Defined Renal Cell Carcinomas.

Kidney tumors comprise a broad spectrum of different histopathological entities, with more than 0.4 million newly diagnosed cases each year, mostly in middle-aged and older men. Based on the description of the 2022 World Health Organization (WHO) classification of renal cell carcinoma (RCC), some new categories of tumor types have been added according to their specific molecular typing. However, studies on these types of RCC are still superficial, many types of these RCC currently lack accurate diagnostic standards in the clinic, and treatment protocols are largely consistent with the treatment guidelines for clear cell RCC (ccRCC), which might result in worse treatment outcomes for patients with these types of molecularly defined RCC. In this article, we conduct a narrative review of the literature published in the last 15 years on molecularly defined RCC. The purpose of this review is to summarize the clinical features and the current status of research on the detection and treatment of molecularly defined RCC.

Insufficient epitope-specific T cell clones are responsible for impaired cellular immunity to inactivated SARS-CoV-2 vaccine in older adults.

Aging is a critical risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy. The immune responses to inactivated vaccine for older adults, and the underlying mechanisms of potential differences to young adults, are still unclear. Here we show that neutralizing antibody production by older adults took a longer time to reach similar levels in young adults after inactivated SARS-CoV-2 vaccination. We screened SARS-CoV-2 variant strains for epitopes that stimulate specific CD8 T cell response, and older adults exhibited weaker CD8 T-cell-mediated responses to these epitopes. Comparison of lymphocyte transcriptomes from pre-vaccinated and post-vaccinated donors suggested that the older adults had impaired antigen processing and presentation capability. Single-cell sequencing revealed that older adults had less T cell clone expansion specific to SARS-CoV-2, likely due to inadequate immune receptor repertoire size and diversity. Our study provides mechanistic insights for weaker response to inactivated vaccine by older adults and suggests the need for further vaccination optimization for the old population.

Antiviral effect and mechanism of Phillyrin and its reformulated FS21 against influenza.

Background: Influenza virus causes significant morbidity and mortality with pandemic threat. Oleaceae Fructus Forsythiae is a medicinal herb. This study aimed to investigate antiviral effect of Phillyrin, a purified bioactive compound from this herb, and its reformulated preparation FS21 against influenza and its mechanism. Methods: Madin-Darby Canine Kidney (MDCK) cells were infected by one of six influenza viruses: five influenza A viruses (IAVs: three H1N1 and two H3N2) and one influenza B virus (IBV). Virus-induced cytopathic effects were observed and recorded under microscope. Viral replication and mRNA transcription were evaluated by quantitative polymerase chain reaction (qPCR) and protein expression by Western blot. Infectious virus production was assessed using TCID50 assay, and IC50 was calculated accordingly. Pretreatment and time-of-addition experiments with Phillyrin or FS21 added 1 h before or in early (0-3 h), mid (3-6 h), or late (6-9 h) stages of viral infection were performed to assess their antiviral effects. Mechanistic studies included hemagglutination and neuraminidase inhibition, viral binding and entry, endosomal acidification, and plasmid-based influenza RNA polymerase activity. Results: Phillyrin and FS21 had potent antiviral effects against all six IAV and IBV in a dose-dependent manner. Mechanistic studies showed that both suppressed influenza viral RNA polymerase with no effect on virus-mediated hemagglutination inhibition, viral binding or entry, endosomal acidification, or neuraminidase activity. Conclusions: Phillyrin and FS21 have broad and potent antiviral effects against influenza viruses with inhibition of viral RNA polymerase as the distinct antiviral mechanism.

Clinical Characteristics and Current Status of Treatment for Recurrent Bladder Cancer after Surgeries on Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) is a relatively rare, but highly malignant, disease with an estimated annual incidence of 2 cases per 100,000 people. The main surgical treatment modalities for UTUC are radical nephroureterectomy (RNU) with bladder cuff resection. After surgery, intravesical recurrence (IVR) can occur in up to 47% of patients, and 75% of them present with non-muscle invasive bladder cancer (NMIBC). However, there are few studies focused on the diagnosis and treatment of postoperatively recurrent bladder cancer for patients with previous UTUC history (UTUC-BC), and many of the influencing factors are still controversial. In this article, we performed a narrative review of the recent literature, mainly summarizing the factors influencing postoperative IVR in patients with UTUC and discussing the subsequent prevention, monitoring, and treatment tools for it.

Biological and physiological responses of two Bradysia pests, Bradysia odoriphaga and Bradysia difformis, to Dinotefuran and Lufenuron.

Bradysia odoriphaga and Bradysia difformis are destructive root maggots that cause severe losses to vegetables, flowers and edible fungi. Due to the long-term dependence on single pesticides, Bradysia resistance to insecticides has increased, and field control efficacy has decreased obviously. To screen alternative insecticides, and compare the insecticide susceptibility of these two species, we tested the toxicity of eight insecticides to B. odoriphaga and B. difformis, and measured the sublethal effects of Dinotefuran and Lufenuron on life-history parameters and detoxification enzyme activities. Bioassay results indicated that Dinotefuran and Lufenuron had relatively higher toxicity to B. odoriphaga and B. difformis compared to other neonicotinoid and insect growth regulator insecticides, respectively. Significant adverse impacts caused by sublethal concentrations (LC20) of Dinotefuran and Lufenuron on the life-history parameters of F0 and F1 generations of B. odoriphaga and B. difformis were observed. These included reduced survival, prolonged larval development and reduced adult longevity and fecundity. B. odoriphaga had greater resistance and adaptation to insecticides than B. difformis, and an LC20 concentration of Dinotefuran stimulated the reproduction of B. odoriphaga F1 generation and increased the life table parameters. Detoxifying enzymes (CarE and GSTs) and P450 activities fluctuated after a sublethal concentration (Dinotefuran and Lufenuron) treatment, and at the peak value of enzyme activities, the enhancement of detoxifying enzymes of B. odoriphaga was significantly higher than that of B. difformis. These results indicated that Dinotefuran and Lufenuron should be considered as alternatives to other insecticides for control of root maggots. B. odoriphaga exhibited stronger adaptation to insecticides than B. difformis. These data provide guidance for control of root maggots, and the basic information presented here can help reveal the differences in adaptive mechanisms between B. odoriphaga and B. difformis.

Effects of the Entomopathogenic Fungus Mucor hiemalis BO-1 on the Physical Functions and Transcriptional Signatures of Bradysia odoriphaga Larvae.

Mucor hiemalis BO-1 is an entomopathogenic fungus that infects Bradysia odoriphaga, a destructive root maggot. M. hiemalis BO-1 possesses stronger pathogenicity to the larvae than to other stages of B. odoriphaga, and provides satisfactory field control. However, the physiological response of B. odoriphaga larvae to infection and the infection mechanism of M. hiemalis are unknown. We detected some physiological indicators of diseased B. odoriphaga larvae infected by M. hiemalis BO-1. These included changes in consumption, nutrient contents, and digestive and antioxidant enzymes. We performed transcriptome analysis of diseased B. odoriphaga larvae, and found that M. hiemalis BO-1 showed acute toxicity to B. odoriphaga larvae and was as toxic as some chemical pesticides. The food consumption of diseased B. odoriphaga after inoculation with M. hiemalis spores decreased significantly, and there was a significant decrease in total protein, lipid, and carbohydrates in diseased larvae. Key digestive enzymes (protease, α-amylase, lipase, and cellulase) were significantly inhibited during infection. Peroxidase maintained high activity, and the activity of other antioxidant enzymes (catalase, superoxide dismutase, and glutathione S-transferases) first increased and then decreased. Combined with the transcriptional signatures of diseased B. odoriphaga larvae, M. hiemalis BO-1 infection resulted in decreased food consumption, reduced digestive enzyme activity, and altered energy metabolism and material accumulation. Infection was also accompanied by fluctuations in immune function, such as cytochrome P450 and the Toll pathway. Therefore, our results laid a basis for the further study of the interactions between M. hiemalis BO-1 and B. odoriphaga and promoted the genetic improvement of entomopathogenic fungi.