[The role of regulated cell death in renal ischemia-reperfusion injury].

Renal ischemia-reperfusion injury (IRI) is histologically characterized by tubular cell death. Diverse pathways of regulated cell death (RCD) have been reported to contribute to renal IRI in recent studies. In this review, we discuss the signaling pathways, regulators and crosstalk of RCD, including necroptosis, ferroptosis and pyroptosis, and their role in renal IRI in order to pave the way for new therapeutic opportunities.

Comparative analysis of the diffusion kurtosis imaging and diffusion tensor imaging in grading gliomas, predicting tumour cell proliferation and IDH-1 gene mutation status.

INTRODUCTION: Few studies have applied diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) for the comprehensive assessment of gliomas [tumour grade, isocitrate dehydrogenase-1 (IDH-1) mutation status and tumour proliferation rate (Ki-67)]. This study describes the efficacy of DKI and DTI to comprehensively evaluate gliomas, compares their results. METHODS: Fifty-two patients (18 females; median age, 47.5 years) with pathologically proved gliomas were prospectively included. All cases underwent DKI examination. DKI (mean kurtosis: MK, axial kurtosis: Ka, radial kurtosis: Kr) and DTI (mean diffusivity: MD, fractional anisotropy: FA) maps of each metric was derived. Three ROIs were manually drawn. RESULTS: MK, Ka, Kr and FA were significantly higher in HGGs than in LGGs, whereas MD was significantly lower in HGGs than in LGGs (P < 0.01). ROC analysis demonstrated that MK (specificity: 100% sensitivity: 79%) and Ka (specificity: 96% sensitivity: 82%) had the same and highest (AUC: 0.93) diagnostic value. Moreover, MK, Ka, and Kr were significantly higher in grade III than II gliomas (P ≦ 0.01). Further, DKI and DTI can significantly identify IDH-1 mutation status (P ≦ 0.03). Ka (sensitivity: 74%, specificity: 75%, AUC: 0.72) showed the highest diagnostic value. In addition, DKI metrics and MD showed significant correlations with Ki-67 (P ≦ 0.01) and Ka had the highest correlation coefficient (rs = 0.72). CONCLUSIONS: Compared with DTI, DKI has great advantages for the comprehensive assessment of gliomas. Ka might serve as a promising imaging index in predicting glioma grading, tumour cell proliferation rate and IDH-1 gene mutation status.

Genome sequence of Isaria javanica and comparative genome analysis insights into family S53 peptidase evolution in fungal entomopathogens.

The fungus Isaria javanica is an important entomopathogen that parasitizes various insects and is effective for pest control. In this study, we sequenced and assembled the genomes (IJ1G and IJ2G) of two I. javanica strains isolated from different insects. The genomes were approximately 35 Mb in size with 11,441 and 11,143 protein-coding genes, respectively. Using a phylogenomic approach, we evaluated genome evolution across five entomopathogenic fungi in Cordycipitaceae. By comparative genome analysis, it was found that family S53 serine peptidases were expanded in Cordycipitaceae entomopathogens, particularly in I. javanica. Gene duplication events were identified based on phylogenetic relationships inferred from 82 S53 peptidases within six entomopathogenic fungal genomes. Moreover, we found that carbohydrate-active enzymes and proteinases were the largest secretory protein groups encoded in the I. javanica genome, especially chitinases (GH18), serine and aspartic peptidases (S53, S08, S10, A01). Pathogenesis-related genes and genes for bacterial-like toxins and secondary metabolites were also identified. By comparative transcriptome analysis, differentially expressed genes in response to insect nutrients (in vitro) were identified. Moreover, most S53 peptidases were detected to be significantly upregulated during the initial fungal infection process in insects (in vivo) by RT-qPCR. Our results provide new clues about understanding evolution of pathogenic proteases and may suggest that abundant S53 peptidases in the I. javanica genome may contribute to its effective parasitism on various insects.

A study of neurite orientation dispersion and density imaging in wilson's disease.

BACKGROUND: Previous studies have indicated that neurite orientation dispersion and density imaging (NODDI) could be used as a biomarker for detecting microstructural changes of brain. PURPOSE: To quantitatively evaluate the changes in basal ganglia (BG) and thalamus in Wilson's disease (WD) by NODDI and assess the correlation between parameters and disease severity. STUDY TYPE: Prospective case-control study. POPULATION: In total, 24 WD patients and 25 age- and sex-matched normal controls were involved in this study. FIELD STRENGTH/SEQUENCE: EPI diffusion-weighted MR images (b-values = 0, 1000, and 2000 with 30 diffusion gradient directions) were acquired on a 3T scanner. ASSESSMENT: Diffusion data were analyzed using voxel-based analysis. NODDI indices including intracellular volume fraction (Vic), orientation dispersion index (ODI), and isotropic volume fraction (Viso) were estimated from the BG and thalamus. The disease severity was assessed by two experienced neurologists based on the Global Assessment Scale (GAS). The relative importance of NODDI indices in diagnosing WD and predictive accuracy were also analyzed. STATISTICAL TESTING: The Shapiro-Wilk test, Student's t-test, χ2 test, Mann-Whitney-Wilcoxon test, Spearman rank correlation coefficient analysis and random-forest analysis were used for statistical analyses. RESULTS: The Vic and ODI in the BG and thalamus were significantly lower in WD patients than normal controls, while the Viso in the BG and thalamus were significantly higher (P < 0.01). The Vic in the putamen and ODI in the globus pallidus were negatively correlated with clinical severity (rvic = -0.727, P < 0.001; rodi = -0.705, P < 0.001). The Vic in the putamen was the most valuable predictor for diagnosing WD and the prediction accuracy of NODDI was 95.92%. DATA CONCLUSION: NODDI can effectively evaluate the changes of microstructure and metabolism during copper deposition in WD, and thus, it is likely to be useful in detecting the changes in the brain of this disease and assessing its progression. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2018;48:423-430.

[Research progress of HCV NS5A complex inhibitors].

Direct acting antivirals against the hepatitis C virus (HCV) have been developed and the field has been under a rapid progress in recent years. Especially, HCV inhibitors targeting nonstructural 5A (NS5A) protein are attracting much attention due to the potent antiviral activity, fast viral clearance and broad antiviral spectrum. This article is prepared to cover the main progress of HCV NS5 A complex inhibitors in the market since 2010. The pharmaceutical characteristics of diverse compounds are described and summarized according to their different chemotypes.

[Synthesis and biological activity of substituted xanthines as DPP-â £ inhibitors].

In order to find more potential DPP-IV inhibitor, a series of xanthine-scaffold analogs of linagliptin, an approved antidiabetes drug, were designed and synthesized for SAR study. All compounds with a concentration of 50 nmol·L(-1) showed the inhibitory activity against DPP-IV enzyme in vitro, and the inhibition rate of compounds 1a, 1d and 1f was over 50%. Virtual docking was also performed to facilitate the SAR analysis of these substituted xanthines.

Pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma: additional evidence to support they are a single disease with variation in the histologic spectrum.

Pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) are two rare indolent B-cell lymphomas with overlapping features. Recently, cases showing hybridizing features of PTFL and PNMZL have been reported. Herein, we retrospectively analyzed the clinicopathologic features of 59 patients, including 39 with PTFL, 5 with PNMZL, and 15 with mixed-type tumors (MTT). And next-generation sequencing analysis was performed on 3 PTFL, 2 PNMZL, and 2 MTT cases. In addition, previously published mutational data of 96 PTFLs, 25 PNMZLs, and 46 MTTs were also analyzed. There were 52 male and 7 female patients, with a median age of 17 years. Most patients (96.6%) had lymph node involvement in the head and neck region and were diagnosed with stage I disease. Among the 50 patients (85%) with telephone follow-up, 44 (88%) adopted a watch-and-wait strategy after surgical resection of the lesions. Only one PTFL patient experienced a relapse 6 months after diagnosis. Microscopically, not only the MTT cases showed a composite form of enlarged follicles and interfollicular lymphocytic proliferation producing a progressively transformed germinal center (PTGC) pattern, but also focal follicles with a PTGC-like pattern were observed in PTFL cases. Genetically, the most frequently mutated genes were TNFRSF14 (in 3 PTFLs and 2 MTTs), MAP2K1 (in 2 PTFLs, 1 PNMZL and 1 MTT), and IRF8 (in 2 MTTs and 1 PNMZL). Based on the similar or overlapping clinical, pathologic, and genetic features, PTFL and PNMZL are likely to represent two different histologic patterns of the same disease.

Facilitating Layered Oxide Cathodes Based on Orbital Hybridization for Sodium-Ion Batteries: Marvelous Air Stability, Controllable High Voltage, and Anion Redox Chemistry.

Layered oxides have become the research focus of cathode materials for sodium-ion batteries (SIBs) due to the low cost, simple synthesis process, and high specific capacity. However, the poor air stability, unstable phase structure under high voltage, and slow anionic redox kinetics hinder their commercial application. In recent years, the concept of manipulating orbital hybridization has been proposed to simultaneously regulate the microelectronic structure and modify the surface chemistry environment intrinsically. In this review, the hybridization modes between atoms in 3d/4d transition metal (TM) orbitals and O 2p orbitals near the region of the Fermi energy level (EF) are summarized based on orbital hybridization theory and first-principles calculations as well as various sophisticated characterizations. Furthermore, the underlying mechanisms are explored from macro-scale to micro-scale, including enhancing air stability, modulating high working voltage, and stabilizing anionic redox chemistry. Meanwhile, the origin, formation conditions, and different types of orbital hybridization, as well as its application in layered oxide cathodes are presented, which provide insights into the design and preparation of cathode materials. Ultimately, the main challenges in the development of orbital hybridization and its potential for the production application are also discussed, pointing out the route for high-performance practical sodium layered oxide cathodes.

Anion Effect on the CuII-Neocuproine Mediator and Its Electrocatalysts for Dye-Sensitized Solar Cells: Polymeric Chalcogenides of PEDOT-PEDTT and [Ag2(SePh)2]n.

The synthetical methodology for the [Cu(dmp)2]2+/1+ (dmp = 2,9-dimethyl-1,10-phenanthroline; neocuproine) complexes has been systematically investigated by using various copper precursors, including CuCl2, Cu(NO3)2, and Cu(ClO4)2. After an anion exchange to trifluoromethanesulfonimide (TFSI), the tetra-coordinated CuII(dmp)2(TFSI)2-Cu(ClO4)2 (7.43%) outperformed the penta-coordinated CuII(dmp)2(TFSI)(NO3)-Cu(NO3)2 (4.30%) and CuII(dmp)2(TFSI)(Cl)-CuCl2. Polymeric chalcogenides, including a conducting copolymeric electrode of PEDOT-PEDTT [PEDOT = poly(3,4-ethylenedioxythiophene); PEDTT = poly(3,4-ethylenedithiothiophene)] and a coordination polymeric electrode of silver bezeneselenolate ([Ag2(SePh)2]n; mithrene), are introduced as the electrocatalysts for [Cu(dmp)2]2+/1+ for the first time. After optimization, dye-sensitized solar cells (DSSCs) based on carbon cloth (CC)/AgSePh-30 (10.18%) showed superior electrocatalytic ability compared to the benchmark CC/Pt (7.43%) due to numerous active sites provided by electron-donating Se atoms, high film roughness, and bottom-up 2D charge transfer routes. The DSSC based on CC/PEDTT-50 (10.38%) also outperformed CC/Pt due to numerous active sites provided by electron-donating S atoms and proper energy band structure. This work sheds light on the future design and synthesis in Cu-complex mediators and functional polymeric chalcogenides for high-performance DSSCs.

Interfacial Spinel Local Interlocking Strategy Toward Structural Integrity in P3 Oxide Cathodes.

P3-layered transition oxide cathodes have garnered considerable attention owing to their high initial capacity, rapid Na+ kinetics, and less energy consumption during the synthesis process. Despite these merits, their practical application is hindered by the substantial capacity degradation resulting from unfavorable structural transformations, Mn dissolution and migration. In this study, we systematically investigated the failure mechanisms of P3 cathodes, encompassing Mn dissolution, migration, and the irreversible P3-O3' phase transition, culminating in severe structural collapse. To address these challenges, we proposed an interfacial spinel local interlocking strategy utilizing P3/spinel intergrowth oxide as a proof-of-concept material. As a result, P3/spinel intergrowth oxide cathodes demonstrated enhanced cycling performance. The effectiveness of suppressing Mn migration and maintaining local structure of interfacial spinel local interlocking strategy was validated through depth-etching X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and in situ synchrotron-based X-ray diffraction. This interfacial spinel local interlocking engineering strategy presents a promising avenue for the development of advanced cathode materials for sodium-ion batteries.

Nickel Nanoparticles Protruding from Molybdenum Carbide Micropillars with Carbon Layer-Protected Biphasic 0D/1D Heterostructures for Efficient Water Splitting.

It remains a tremendous challenge to achieve high-efficiency bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) for hydrogen production by water splitting. Herein, a novel hybrid of 0D nickel nanoparticles dispersed on the one-dimensional (1D) molybdenum carbide micropillars embedded in the carbon layers (Ni/Mo2C@C) was successfully prepared on nickel foam by a facile pyrolysis strategy. During the synthesis process, the nickel nanoparticles and molybdenum carbide were simultaneously generated under H2 and C2H2 mixed atmospheres and conformally encapsulated in the carbon layers. Benefiting from the distinctive 0D/1D heterostructure and the synergistic effect of the biphasic Mo2C and Ni together with the protective effect of the carbon layer, the reduced activation energy barriers and fast catalytic reaction kinetics can be achieved, resulting in a small overpotential of 96 mV for the HER and 266 mV for the OER at the current density of 10 mA cm-2 together with excellent durability in 1.0 M KOH electrolyte. In addition, using the developed Ni/Mo2C@C as both the cathode and anode, the constructed electrolyzer exhibits a small voltage of 1.55 V for the overall water splitting. The novel designed Ni/Mo2C@C may give inspiration for the development of efficient bifunctional catalysts with low-cost transition metal elements for water splitting.

Developing an abnormal high-Na-content P2-type layered oxide cathode with near-zero-strain for high-performance sodium-ion batteries.

Layered transition metal oxides (NaxTMO2) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, NaxTMO2 suffer from multiple phase transitions and Na+/vacancy ordering upon Na+ insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g-1 at 0.2C and 97 mA h g-1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na+ storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials.

URA3 as a Selectable Marker for Disruption and Functional Assessment of PacC Gene in the Entomopathogenic Fungus Isaria javanica.

An effective selection marker is necessary for genetic engineering and functional genomics research in the post-genomic era. Isaria javanica is an important entomopathogenic fungus with a broad host range and prospective biocontrol potentials. Given that no antibiotic marker is available currently in this fungus, developing an effective selection marker is necessary. In this study, by applying overlap PCR and split-marker deletion strategy, combining PEG-mediated protoplasm transformation method, the uridine auxotrophy gene (ura3) in the I. javanica genome was knocked out. Then, using this transformation system, the pH response transcription factor gene (IjpacC) was disrupted successfully. Loss of IjpacC gene results in an obvious decrease in conidial production, but little impact on mycelial growth. The virulence of the ΔIjpacC mutant on caterpillars is similar to that of the wild-type strain. RT-qPCR detection shows that expression level of an acidic-expressed S53 gene (IF1G_06234) in ΔIjpacC mutant is more significantly upregulated than in the wild-type strain during the fungal infection on caterpillars. Our results indicate that a markerless transformation system based upon complementation of uridine auxotrophy is successfully developed in I. javanica, which is useful for exploring gene function and for genetic engineering to enhance biological control potential of the fungus.

Effects of transgenerational photoperiod experience on the reproduction and development of Anastatus orientalis, an egg parasitoid of the spotted lanternfly.

Transgenerational experience can affect a range of natural enemies' life-history traits and can be involved in the control of developmental plasticity. As a major egg parasitoid of the spotted lanternfly, Lycorma delicatula (Hemiptera: Fulgoridae), the wasp Anastatus orientalis (Hymenoptera: Eupelmidae) is effective at suppressing its host populations. The reproductive and developmental traits of A. orientalis is known to depend on photoperiod conditions, but transgenerational photoperiodic effects have yet to be evaluated. To evaluate the transgenerational photoperiodic effects on A. orientalis, we assessed wasp adult longevity, female fecundity, sex ratio, and diapause rate over three consecutive generations under different experimental photoperiods (L16:D8, L12:D12, and L8:D16), using Antheraea pernyi (Lepidoptera: Saturniidae) eggs as hosts. The results suggest that transgenerational experience significantly impacts several biological parameters of progeny. All parasitoids entered a diapause under the long photoperiod condition (i.e., L16:D8), after which the number of female parasitoids and fecundity of the 2nd and 3rd generations increased significantly as compared to the 1st generation. With the long photoperiod conditions, the female ratio rose from 68.1% (1st generation) to 86.0% (3rd generation) and the progeny per females increased from 35.8 to 75.7. However, adult longevity of females and males were shortened significantly. With the intermediate photoperiod (L12:D12) conditions, fecundity and sex ratio of the 2nd and 3rd generations increased significantly as compared to the 1st generation. With the short photoperiod (L8:D16) conditions, there were no significant differences in fecundity among three generations, but sex ratio of the 2nd and 3rd generations increased significantly as compared to the 1st generation. These results on transgenerational photoperiodic effects can be applied to improve laboratory rearing efficiency of parasitoids and to better understand population dynamics in the field across a latitudinal gradient.

Assessing the impact of educational methods on influenza vaccine uptake and patient knowledge and attitudes: a randomised controlled trial.

Introduction: Although influenza vaccination reduces rates of pneumonia, hospitalisation and mortality, influenza vaccination uptake remains low in older patients. The primary aim was to compare individualised counselling with educational pamphlets alone in improving influenza vaccination uptake. The secondary aims were to evaluate knowledge and attitudes towards influenza vaccination and factors influencing uptake. Methods: A randomised controlled study was conducted in two government polyclinics with 160 participants per arm. Patients aged 65 years and above attending for doctor consultation were recruited. All participants received an educational pamphlet on influenza vaccination. The intervention group received additional face-to-face counselling. Participants filled a pre- and postintervention questionnaire assessing knowledge of influenza and attitudes towards the vaccine. Follow-up calls and verification of electronic records was done at three months to determine actual vaccine uptake. Results: At three months, 16 (10%) patients in the intervention group and 20 (12.5%) patients in the control group had completed influenza vaccination (P = 0.48). Factors positively associated with vaccine uptake were willingness to receive vaccination immediately after intervention (adjusted odds ratio [OR] 12.15, 95% confidence interval [CI] 4.42-33.38), and male gender (adjusted OR 2.96, 95% CI 1.23-7.12). Individualised counselling was more effective in improving knowledge (P < 0.01). Overall knowledge scores did not influence actual vaccine uptake rates. (adjusted OR 1.10 [0.90-1.3]). Conclusion: Both arms of patient education increased uptake of influenza vaccination. Individualised counselling was not superior to pamphlets alone in improving uptake. Performing vaccination at the initial point of contact improves actual uptake rates.

Prevalence and healthcare utilization in managing herpes zoster in primary care: a retrospective study in an Asian urban population.

Herpes zoster (HZ) causes significant morbidity, particularly in older adults. With the advent of a recombinant zoster vaccine, HZ is potentially preventable. However, data on HZ burden and healthcare utilization in primary care populations remains scarce. This study described the prevalence and healthcare utilization in managing HZ in a developed community. A retrospective database review was conducted across a cluster of 8 public primary care clinics in urban Singapore. Data of multi-ethnic Asian patients with a diagnosis code of "herpes zoster" from 2018 to 2020 was extracted from their electronic medical records. Socio-demographic, clinical, visitation, medical leave, prescription, and referral data were analyzed. A total of 2,987 out of 737,868 individuals were diagnosed with HZ over 3 years. The mean age was 59.9 (SD + 15.5) years; 49.2% were male; 78.5% Chinese, 12.2% Malay, and 4.1% Indian. The prevalence was 221, 224, 203 per 100,000 persons in 2018, 2019, and 2020, respectively. The 70 to 79-year age group had the highest prevalence (829/100,000) across 3 years. Oral acyclovir (median daily dose 4,000 mg; median duration 7 days) and topical acyclovir were prescribed in 71.6 and 47.6%, respectively. Analgesia prescribed were gabapentin (41.0%), paracetamol combinations (30.1%), oral NSAIDs (23.7%), opioids (6.0%), and tricyclic antidepressants (1.9%). Most individuals consulted only once (84.3%); 32.7% of them required medical leave and 5.6% had more than 7 days of absenteeism. HZ-related referrals to the hospital were required in 8.9% (4.9% emergency, 2.8% ophthalmology). The findings of this study suggest a need for HZ vaccination among older age groups. Visitation and referral rates were low. The use of topical acyclovir was uncovered, and further research should evaluate the underlying reasons, benefits, and harms of such practice. The use of analgesia combinations may be explored further.

A Universal Strategy Based on Bridging Microstructure Engineering and Local Electronic Structure Manipulation for High-Performance Sodium Layered Oxide Cathodes.

Due to their high capacity and sufficient Na+ storage, O3-NaNi0.5Mn0.5O2 has attracted much attention as a viable cathode material for sodium-ion batteries (SIBs). However, the challenges of complicated irreversible multiphase transitions, poor structural stability, low operating voltage, and an unstable oxygen redox reaction still limit its practical application. Herein, using O3-NaNi0.5Mn0.5-xSnxO2 cathode materials as the research model, a universal strategy based on bridging microstructure engineering and local electronic structure manipulation is proposed. The strategy can modulate the physical and chemical properties of electrode materials, so as to restrain the unfavorable and irreversible multiphase transformation, improve structural stability, manipulate redox potential, and stabilize the anion redox reaction. The effect of Sn substitution on the intrinsic local electronic structure of the material is articulated by density functional theory calculations. Meanwhile, the universal strategy is also validated by Ti substitution, which could be further extrapolated to other systems and guide the design of cathode materials in the field of SIBs.

Sodium Layered/Tunnel Intergrowth Oxide Cathodes: Formation Process, Interlocking Chemistry, and Electrochemical Performance.

Manganese-based layered oxides are prospective cathode materials for sodium-ion batteries (SIBs) due to their low cost and high theoretical capacities. The biphasic intergrowth structure of layered cathode materials is essential for improving the sodium storage performance, which is attributed to the synergistic effect between the two phases. However, the in-depth formation mechanism of biphasic intergrowth materials remains unclear. Herein, the layered/tunnel intergrowth Na0.6MnO2 (LT-NaMO) as a model material was successfully prepared, and their formation processes and electrochemical performance were systematically investigated. In situ high-temperature X-ray diffraction displays the detailed evolution process and excellent thermal stability of the layered/tunnel intergrowth structure. Furthermore, severe structural strain and large lattice volume changes are significantly mitigated by the interlocking effect between the phase interfaces, which further enhances the structural stability of the cathode materials during the charging/discharging process. Consequently, the LT-NaMO cathode displays fast Na+ transport kinetics with a remarkable capacity retention of ∼70.5% over 300 cycles at 5C, and its assembled full cell with hard carbon also exhibits high energy density. These findings highlight the superior electrochemical performance of intergrowth materials due to interlocking effects between layered and tunnel structures and also provide unique insights into the construction of intergrowth cathode materials for SIBs.

Exploratory Survey of Spotted Lanternfly (Hemiptera: Fulgoridae) and Its Natural Enemies in China.

An invasive population of spotted lanternfly (SLF), Lycorma delicatula White, was first noted in North America in Pennsylvania in 2014, and by September 2020 populations had spread to six additional states. To develop a biocontrol program to aid in the management of the pest, exploratory surveys for SLF natural enemies in its native range were carried out in 27 provinces and other administrative regions of China from 2015 to 2019. Naturally laid egg masses were collected and sentinel SLF egg masses were deployed to attract egg parasitoids, and yellow sticky traps were used to collect SLF nymphs to discover and determine the parasitism rates of nymphal parasitoids. Results show that SLF is widely distributed in China (22 provinces and regions) and that the population densities in northeast China are higher than in southern and western China. An egg parasitoid, Anastatus orientalis Yang (Hymenoptera: Eupelmidae), and a nymphal parasitoid, Dryinus sinicus Olmi (Hymenoptera: Dryinidae), were collected. Anastatus orientalis was reared from SLF eggs in seven provinces in China with parasitoid emergence rates ranging from 4.0 to 15.5% (or 17.6 to 37.3% if including only egg masses that had at least some parasitism). There were significant differences in parasitoid emergence rates between sites associated with factors including habitat and host plants. Dryinus sinicus was discovered in eight cities across six provinces. The percentage of SLF nymphs parasitized by D. sinicus were 31.1, 23.3, and 0% in Tai'an, Shandong Province, Beijing City, and Yan'an, Shaanxi Province, respectively. These two parasitoids are promising natural enemies that are being considered as potential biocontrol agents of invasive populations of SLF.

Responses to crizotinib and cabozantinib in patient with lung adenocarcinoma harboring mesenchymal-epithelial transition factor exon 14 skipping mutation: A case report.

RATIONALE: Lung cancer is a leading cause of cancer-related mortality worldwide. Currently, targeted therapy has proved highly efficient in the treatment of advanced non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor (MET) is considered a validated molecular target in NSCLC. Given the low incidence of MET exon 14 skipping mutation, the planning of precision treatment for patients is a clinical problem that needs to be solved. In this report, we present a MET-positive case that benefited from crizotinib and cabozantinib treatment. PATIENT CONCERNS: A 77-year-old patient was diagnosed with lung adenocarcinoma in our hospital. Positron emission tomography-computed tomography (PET-CT) showed a right upper lobe mass (58 × 56 mm, SUVmax 15.6), right hilar enlarged lymph nodes, and multiple bone and left adrenal metastases (c-T3N1M1c). DIAGNOSES: MET exon 14 mutation (exon14, c.2888-1G>C) was examined using the lung puncture sample by next generation sequencing. Therefore, the patient was diagnosed with late-stage lung adenocarcinoma with MET exon14 skipping gene mutation. INTERVENTIONS: Crizotinib was given as the first-line treatment from August 2019. Considering the resistance of crizotinib, cabozantinib was given for second-line treatment. OUTCOMES: Crizotinib was administered (250 mg bid) for 8 months, and her disease achieved partial regression (PR) and progression-free survival (PFS), which lasted for 8 months. The patient also reached PR after the second-line treatment with cabozantinib, and is currently under follow-up, with an overall survival (OS) of >12 months. LESSONS: As MET exon 14 skipping mutation is rare in clinical practices, MET-TKIs (tyrosine kinase inhibitors) treatment can boost curative effects and improve prognosis of patients with advanced lung adenocarcinoma. This case report supports a rationale for the treatment of lung adenocarcinoma patients with a MET exon 14 skipping mutation and provides alternative treatment options for these types of NSCLC patients.