Covariation of preadult environmental exposures, adult brain imaging phenotypes, and adult personality traits.

Exposure to preadult environmental exposures may have long-lasting effects on mental health by affecting the maturation of the brain and personality, two traits that interact throughout the developmental process. However, environment-brain-personality covariation patterns and their mediation relationships remain unclear. In 4297 healthy participants (aged 18-30 years), we combined sparse multiple canonical correlation analysis with independent component analysis to identify the three-way covariation patterns of 59 preadult environmental exposures, 760 adult brain imaging phenotypes, and five personality traits, and found two robust environment-brain-personality covariation models with sex specificity. One model linked greater stress and less support to weaker functional connectivity and activity in the default mode network, stronger activity in subcortical nuclei, greater thickness and volume in the occipital, parietal and temporal cortices, and lower agreeableness, consciousness and extraversion as well as higher neuroticism. The other model linked higher urbanicity and better socioeconomic status to stronger functional connectivity and activity in the sensorimotor network, smaller volume and surface area and weaker functional connectivity and activity in the medial prefrontal cortex, lower white matter integrity, and higher openness to experience. We also conducted mediation analyses to explore the potential bidirectional mediation relationships between adult brain imaging phenotypes and personality traits with the influence of preadult environmental exposures and found both environment-brain-personality and environment-personality-brain pathways. We finally performed moderated mediation analyses to test the potential interactions between macro- and microenvironmental exposures and found that one category of exposure moderated the mediation pathways of another category of exposure. These results improve our understanding of the effects of preadult environmental exposures on the adult brain and personality traits and may facilitate the design of targeted interventions to improve mental health by reducing the impact of adverse environmental exposures.

Mapping the metabolic characteristics of probiotic-fermented Ganoderma lucidum and its protective mechanism against Cd-induced nephrotoxicity.

An animal model of Cd-induced kidney damage was designed to investigate the nephroprotective potential of the probiotic-fermented Ganoderma lucidum (FGL) via metabonomic analysis. The results showed that FGL enhanced sugar and amino acid metabolism. The interaction of Ganoderma lucidum (GL) and probiotics efficiently elevated short-chain fatty acid production following gut microbiota fermentation. The current data revealed that the FGL intervention alleviated Cd-induced nephrotoxicity via elevating the activity of antioxidant enzymes and decreasing the levels of pro-inflammatory and apoptotic factors. Based on transcriptome analysis, FGL intervention mediated renal dysfunction via decreasing the expressions of Nos2, Tnfsf14, S100a9, Map3k6 and Hk3, which were involved in oxidative stress, inflammatory response and the apoptosis process. The current study highlights a new approach for achieving positive nephroprotection via natural product intervention.

Asymmetry of individual activity promotes cooperation in the spatial prisoner's dilemma game.

We consider an aspiration-based asymmetric individual activity co-evolutionary prisoner's dilemma game model on the square lattice. In detail, each player has an individual weight that evolves with its strategy. We introduce an asymmetric setting that only µ fractions of players in the network chosen to be active can update their individual weights according to whether their payoffs satisfy their aspirations. Therefore, our individual weights can be regarded as a type of intrinsic motivation satisfaction. Through Monte Carlo simulations on the square lattice, our co-evolution mechanism has been proven to significantly promote cooperation. Furthermore, we find that the moderate µ leads to the highest cooperation level. By dividing the players into four types according to their strategies and weights, we prove that the inversion of the dominant relationship between cooperators and defectors with low weights leads to a conversion cycle of the four types of players, which enhances spatial reciprocity to promote cooperation. Moderate µ results in an appropriate number of low-weight players in this cycle. Interestingly, our results show that higher weight heterogeneity does not lead to higher levels of cooperation, which is contrary to the intuition formed in the previous work.

Surface Texture Designs to Improve the Core-Veneer Bond Strength of Zirconia Restorations Using Digital Light Processing.

Veneered zirconia ceramics are widely used for dental restorations. However, the relatively poor bonding strength between the ceramic core and veneer porcelain remains a common problem in clinical applications. To address this issue, this study focused on enhancing the core-veneer bond strength of zirconia restorations through the implementation of surface textures using digital light processing (DLP) technology. The light intensity was precisely tuned to optimize mechanical strength and minimize light scattering. Subsequently, hexagonal or square grids were printed on the surface of the zirconia ceramic core. Following veneering procedures, the shear bond strength (SBS) test was conducted using a universal testing machine. Dates were compared using analysis of variance (ANOVA) and the least significant difference (LSD) test. Furthermore, optical microscopy and scanning electron microscopy (SEM) were used to examine the failure modes and observe the cross-sectional structures, respectively. The results indicated that the presence of a 0.09 mm high hexagon grid led to a significant 21% increase in the SBS value. However, grids with heights of 0.2 and 0.3 mm showed less improvement, owing to the formation of large defects at the interface during the fusion process. This study demonstrated the potential of DLP technology in preparing zirconia ceramics with complex structures and high mechanical strength, thereby offering promising solutions for overcoming challenges associated with dental applications.

Porphyrin-based Bi-MOFs with Enriched Surface Bi Active Sites for Boosting Photocatalytic CO2 Reduction.

The inherent challenges in using metal-organic frameworks (MOFs) for photocatalytic CO2 reduction are the combination of wide-range light harvesting, efficient charge separation and transfer as well as highly exposed catalytic active sites for CO2 activation and reduction. We present here a promising solution to satisfy these requirements together by modulating the crystal facet and surface atomic structure of a porphyrin-based bismuth-MOF (Bi-PMOF). The series of structural and photo-electronic characterizations together with photocatalytic CO2 reduction experiment collectively establish that the enriched Bi active sites on the (010) surface prefer to promote efficient charge separation and transfer as well as the activation and reduction of CO2. Specifically, the Bi-PMOFs-120-F with enriched surface Bi active sites exhibits optimum photocatalytic CO2 reduction performance to CO (28.61 umol·h-1g-1) and CH4 (8.81 umol·h-1g-1). This work provides new insights to synthesize highly efficient main group p-block metal Bi-MOF photocatalysts for CO2 reduction through a facet-regulation strategy and sheds light on the surface structure-activity relationships of the MOFs.

Application of a fiber Bragg grating temperature sensing method based on support vector regression optimized by a genetic algorithm for the decreasing external ambient temperature case.

We studied the application of the fiber Bragg grating (FBG) temperature sensing method based on support vector regression optimized by a genetic algorithm (GA-SVR) for constant and decreasing external ambient temperature cases by simulation. The external ambient temperature could be retrieved from both the transient FBG wavelength and its corresponding change rate using GA-SVR, before the FBG temperature sensor reached the thermal equilibrium state with the external ambient temperature. FBG wavelengths and their corresponding change rates in the cases of FBG sensor temperatures higher and lower than the external ambient temperature were studied and used to construct the training data set. We found that there exist singularity points in the curves of the wavelength change rate when the FBG sensor temperature is higher than the external ambient temperature in some cases, which is different from the case where the FBG sensor temperature is lower than the external ambient temperature. Its application for sensing the constant and decreasing external ambient temperature in real time was demonstrated with an accuracy of 0.32°C in those two cases. It also indicates that for real applications of this temperature sensing method where the external ambient temperature varies randomly, the FBG sensor temperature changes rather than the external ambient temperature changes play the dominant role. What is more, the demodulation time was decreased to 0.002 s, which is approximately 0.05‱ of the time constant of the FBG temperature sensor. In other words, this method makes it possible to realize the external ambient temperature determination using a time smaller than the time constant of the FBG sensor. The high sensing accuracy and fast demodulation speed are crucial for future high-performance real-time FBG temperature sensing.

Characterization of two novel VIM-type metallo-ß-lactamases, VIM-84 and VIM-85, associated with the spread of IncP-2 megaplasmids in Pseudomonas aeruginosa.

This study aimed to characterize two novel VIM-type metallo-ß-lactamases, VIM-84 and VIM-85, and reveal the important role of the IncP-2 type megaplasmids in the spread of antimicrobial resistance (AMR) genes. VIM-84 and VIM-85 were encoded by two novel genes bla VIM-84 and bla VIM-85 which showed similarity to bla VIM-24. Both bla VIM-84 and bla VIM-85 are harbored into class 1 integrons embedded into the Tn1403 transposon. The bla VIM-85 gene was identified in a megaplasmid, which was related to 17 megaplasmid sequences with sizes larger than 430 kb, deposited previously in Genbank. A comparative analysis of complete plasmid sequences showed highly similar backbone regions and various AMR genes. A phylogenetic tree revealed that these megaplasmids, which were widely distributed globally, were vehicles for the spread of AMR genes. The bla VIM-24, bla VIM-84, and bla VIM-85 genes were cloned into pGK1900, and the recombinant vectors were further transformed into Escherichia coli DH5α and Pseudomonas aeruginosa PAO1. The antimicrobial susceptibility test of the cloning strains showed high levels of resistance to ß-lactams while they remained susceptible to aztreonam. Enzymatic tests revealed that both, VIM-84 and VIM-85, exhibited higher activity in hydrolyzing ß-lactams compared to VIM-24. A D117N mutation found in VIM-24 affected binding to the antibiotics. IMPORTANCE The metallo-ß-lactamases-producing Pseudomonas aeruginosa strains play an important role in hospital outbreaks and the VIM-type enzyme is the most prevalent in European countries. Two novel VIM-type enzymes in our study, VIM-84 and VIM-85, have higher levels of resistance to ß-lactams and greater hydrolytic activities for most ß-lactams compared with VIM-24. Both bla VIM-84 and bla VIM-85 are harbored into class 1 integrons embedded into the Tn1403 transposon. Notably, the genes bla VIM-85 are carried by three different IncP-2-type megaplasmids which are distributed locally and appear responsible for the spread of antimicrobial resistance genes in hospital settings.

Dysfunction of visual novelty detection in physical but not social anhedonia in a non-clinical sample.

Background/objective: Despite its obvious motivational impairment, anhedonia as a transdiagnostic psychopathological construct is accompanied by deficits in attention function. Previous studies have identified voluntary attention anomalies in anhedonia, but its involuntary attention has received less study. Method: Using a visual novelty oddball task, the current event-related potential study assessed electrophysical correlates underlying mismatch detection in anhedonia with a non-clinical sample. Well-matched healthy control (N = 28; CNT), social anhedonia (N = 27; SA), and physical anhedonia (N = 26; PA) groups were presented standard, target, and perceptually novel stimuli while their EEG was recording. Results: The PA group relative to the CNT group exhibited a reduced N2 to novel stimuli but not to target stimuli. In contrast, the SA group as compared to the other two groups showed comparable N2 responses to both target and novel stimuli. Control analyses indicated that these patterns were unaffected by depression symptoms. Conclusions: These findings suggest that anhedonia is a heterogenous construct associated with impairments in early detection of visual novelty in physical but not social anhedonia, highlighting that dysfunction in involuntary attention may play a mediating role in the development, maintenance, and consequences of anhedonia-related psychopathology.

Role of Dental Pulp Stem Cells to Promote Angiogenesis in Cell-based Regenerative Endodontics.

Maintaining the viability and avoiding necrosis of dental pulp are crucial to preserving the structural integrity and functioning of teeth. In recent years, cell-based regenerative endodontics has emerged as a promising approach to achieve this goal and has gained increasing attention in scientific research; however, in the confined space of the root canal system, hypoxic conditions can be both beneficial and detrimental, as they may promote angiogenesis in the graft to some extent but also lead to tissue necrosis if prolonged. Dental pulp stem cells (DPSCs) have been verified as multipotent cells that can promote angiogenesis and are therefore ideal candidates for realising real dental pulp regeneration within root canals. Thus, we focus on the underlying mechanisms of DPSCs to promote angiogenesis and summarise some preclinical studies and clinical trials involving transplanting of DPSCs to achieve real dental pulp regeneration, in the hope that this intractable source of perplexity in regenerative endodontics may be resolved sooner.

WA-ResUNet: A Focused Tail Class MRI Medical Image Segmentation Algorithm.

Medical image segmentation can effectively identify lesions in medicine, but some small and rare lesions cannot be well identified. Existing studies do not take into account the uncertainty of the occurrence of diseased tissue, and the problem of long-tailed distribution of medical data. Meanwhile, the grayscale image obtained from Magnetic Resonance Imaging (MRI) detection has problems, such as the features being difficult to extract and invalid features being difficult to distinguish. In order to solve these problems, we propose a new weighted attention ResUNet (WA-ResUNet) and a class weight formula based on the number of images contained in the class, which improves the performance of the model in the low-frequency class and the overall effect of the model by improving the degree of attention paid to the valid features and invalid ones and rebalancing the learning efficiency among the classes. We evaluated our method on an uterine MRI dataset and compared it with the ResUNet. WA-ResUNet increased Intersection over Union (IoU) in the low-frequency class (Nabothian cysts) by 21.87%, and the overall mIoU increased by more than 6.5%.

A comparative study of posterior cingulate metabolism in patients with mild cognitive impairment due to Parkinson's disease or Alzheimer's disease.

Few comparative studies have assessed metabolic brain changes in cognitive impairment among neurodegenerative disorders, and the posterior cingulate cortex (PCC) is a metabolically active brain region with high involvement in multiple cognitive processes. Therefore, in this study, metabolic abnormalities of the PCC were compared in patients with mild cognitive impairment (MCI) due to Parkinson's disease (PD) or Alzheimer's disease (AD), as examined by proton magnetic resonance spectroscopy (1H-MRS). Thirty-eight patients with idiopathic PD, including 20 with mild cognitive impairment (PDMCI) and 18 with normal cognitive function (PDN), 18 patients with probable mild cognitive impairment (ADMCI), and 25 healthy elderly controls (HCs) were recruited and underwent PCC 1H-MRS scans. Compared with HCs, patients with PDMCI exhibited significantly reduced concentrations of N-acetyl aspartate (NAA), total NAA (tNAA), choline (Cho), glutathione (GSH), glutamate + glutamine (Glx) and total creatine (tCr), while ADMCI cases exhibited significantly elevated levels of myo-inositol (Ins) and Ins/tCr ratio, as well as reduced NAA/Ins ratio. No significant metabolic changes were detected in PDN subjects. Compared with ADMCI, reduced NAA, Ins and tCr concentrations were detected in PDMCI. Besides, ROC curve analysis revealed that tCr concentration could differentiate PDMCI from PDN with an AUC of 0.71, and NAA/Ins ratio could differentiate patients with MCI from controls with normal cognitive function with an AUC of 0.74. Patients with PDMCI and ADMCI exhibited distinct PCC metabolic 1H-MRS profiles. The findings suggested cognitively normal PD patients with low NAA and tCr in the PCC might be at risk of preclinical PDMCI, and Ins and/or NAA/MI ratio in the PCC should be reconsidered a possible biomarker of preclinical MCI in clinical practice. So, comparing PCC's 1H-MRS profiles of cognitive impairment among neurodegenerative illnesses may provide useful information for better defining the disease process and elucidate possible treatment mechanisms.

Electrolytic Graphene Encapsulated CeO2 for Lithium-Sulfur Battery Interlayer Separator.

Rare earth elements and graphene composites exhibit better catalytic properties in energy storage materials. The introduction of rare earth oxide and graphene composites as functional layers into the separator to seal the "shuttle effect" formed by polysulfides during the discharge process has proven to be effective. In this study, we prepared CeO2/graphene composites (labeled as CeG) by intercalation exfoliation and in situ electrodeposition methods simultaneously, in which CeO2 was encapsulated in large folds of graphene, which exhibited good defect levels (ID/IG < 1) and its intrinsically superior physical structure acted as a shielding layer to hinder the shuttle of polysulfides, improving the cycling stability and rate of cell performance. The separator cell with CeG achieves an initial discharge specific capacity of 1133.5 mAh/g at 0.5C, excellent rate performance (978.5 mAh/g at 2C), and long cycling (790 mAh/g after 400 cycles).

Strain-dependent magnetic ordering switching in 2D AFM ternary V-based chalcogenide monolayers.

The lack of macroscopic magnetic moments makes antiferromagnetic materials promising candidates for high-speed spintronic devices. The 2D ternary V-based chalcogenides (VXYSe4; X, Y = Al, Ga) monolayers are investigated based on the density-functional theory and Monte Carlo simulations. The results reveal that the Néel temperature of the VGa2Se4 monolayer is 18 K with zigzag2-antiferromagnetic (AFM) spin ordering. Also, the magnetic ordering of V ions in VAl2Se4 and VAlGaSe4 monolayers prefer zigzag1-AFM coupling with Néel temperature of 47 K and 33 K, respectively. The magnetic anisotropy calculations demonstrate that the easy magnetization axis of the VXYSe4 monolayers is parallel to the y axis. In addition, the VXYSe4 monolayers can be adjusted from the AFM state to the ferromagnetic (FM) state under biaxial stretching, which can be attributed to the competition between d-p-d superexchange and d-d direct exchange caused by the variation of bond length. The transition temperature of VXYSe4 monolayers can be elevated above room temperature with the help of compression strain. In particular, the in-plane magnetic anisotropy is a robust characteristic regardless of the magnitude of the applied biaxial strain. These explorations not only enrich the family of AFM monolayers with excellent stability but also provide distinctive ideas for the performance control of AFM materials and their applications in nanodevices.

Super-resolution multicolor fluorescence microscopy enabled by an apochromatic super-oscillatory lens with extended depth-of-focus.

Planar super-oscillatory lens (SOL), a far-field subwavelength-focusing diffractive device, holds great potential for achieving sub-diffraction-limit imaging at multiple wavelengths. However, conventional SOL devices suffer from a numerical-aperture-related intrinsic tradeoff among the depth of focus (DoF), chromatic dispersion and focusing spot size. Here, we apply a multi-objective genetic algorithm (GA) optimization approach to design an apochromatic binary-phase SOL having a prolonged DoF, customized working distance (WD), minimized main-lobe size, and suppressed side-lobe intensity. Experimental implementation demonstrates simultaneous focusing of blue, green and red light beams into an optical needle of ~0.5λ in diameter and DOF > 10λ at WD = 428 µm. By integrating this SOL device with a commercial fluorescence microscope, we perform, for the first time, three-dimensional super-resolution multicolor fluorescence imaging of the "unseen" fine structures of neurons. The present study provides not only a practical route to far-field multicolor super-resolution imaging but also a viable approach for constructing imaging systems avoiding complex sample positioning and unfavorable photobleaching.

Gastric metastasis from nodular malignant melanoma of the auricle with multigene aberrations: A rare case report and literature review.

Primary malignant melanoma (MM) of the external ear accounts for a low proportion of cases of cutaneous MM, and its incidence in non-white women is very low. The stomach is a rare metastatic site for MM. Gastric metastasis of MM of the external ear is extremely rare, and the associated gene alterations and mechanisms are poorly understood. The present report describes the case of a 58-year-old Asian woman who had a mass on the left auricle for 5 years and was diagnosed with nodular MM with the BRAF V600E mutation after surgical resection. Postoperative metastases to the stomach and descending duodenum appeared 1 year after resection. After 11 months of BRAF-targeted therapy and immunotherapy, the patient developed drug resistance and died from systemic metastases to the brain, lungs, liver, left adrenal gland and peritoneum. Genetic testing revealed additional aberrations in MYB, p16, MYC and PTEN. The clinical characteristics of MM of the external ear and gastric metastatic MM were also summarized through a retrospective literature review. Immunohistochemical staining is critical in the diagnosis of gastric metastasis from MM of the external ear. This disease often requires a multidisciplinary treatment approach, including surgery, targeted therapy and immunotherapy. The present study provides some genetic information about this rare disease and discusses appropriate treatment strategies. The findings of the present study suggests that the surgical margin size, tumor histological type and number of genetic aberrations may be closely associated with metastasis potential, therapeutic efficacy and patient outcome.

Analysis of Adverse Drug Reaction Reports from a Public Hospital in Shanxi Province in 2022.

Objective: Through analyzing the characteristics and influencing factors of adverse drug reactions/adverse events (ADR/ADE) in a hospital to promote rational drug use in the clinic. Methods: A total of 1221 ADR/ADE reports collected from a hospital in 2022 were retrieved through the National Adverse Drug Reaction Monitoring Center. The effective reports were screened according to the Guiding Principles for Collection and Reporting of Individual Adverse Drug Reactions, and classified the standardized drugs. The systems/organs and main clinical symptoms affected by ADR/ADE were classified according to the WHO Glossary of Adverse Drug Reaction Terms. The severity, age and gender, occupational distribution, drug category, route of administration, drug dosage form, system/organ involved, and main clinical symptoms of ADR/ADE reports were analyzed. Results: Among 1221 ADR/ADE reports, 890 cases (75.27%) reported by doctors; 144 cases (11.79%) were serious; Precisely 49.22% of ADR/ADE occurred in patients aged 51 to 70 years old; The highest incidence of adverse reactions was 636 cases (52.09%) by intravenous infusion, 406 cases (33.25%) by oral administration. The top categories of reported cases were anti-infective drugs (29.40%) and anti-tumor drugs (27.52%); Systems/organs involved in ADR/ADE were mainly the skin and its accessories (24.96%) and blood system (21.35%). 166 cases were cured, 893 cases were symptomatic, 160 cases were unknown, and 2 cases had sequelae. Conclusion: The occurrence of ADR/ADE is related to many influencing factors such as age, drug categories, and route of administration. Therefore, it is recommended that hospitals strengthen the monitoring of ADR/ADE, especially the elderly, anti-infective drugs and intravenous administration.

[Corrigendum] Anti­osteoporotic effects of tetramethylpyrazine via promoting osteogenic differentiation and inhibiting osteoclast formation.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 2A on p. 8311, portraying the results of immunostaining experiments for osterix, the 'GIOP' and 'GIOP+TMP (20)' data panels contained overlapping data, such that these images were derived from apparently the same original source, where they were intended to show the results from differently performed experiments. Moreover, in Fig. 3A on p. 8312 showing the results from ALP staining and Alizarin Red S staining experiments, two pairs of apparently overlapping data panels were identified in the Dex 106 M / TMP 50 µM, 100 µM and 200 µM data panels. After having re­examined their original data, the authors have realized that the data featured in Figs. 2A and 3A were assembled incorrectly in these figures. Revised versions of Fig. 2 and 3, now containing replacement data for the experiments shown in Figs. 2A and 3A, are shown on the next page. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 16: 8307­8314, 2017; DOI: 10.3892/mmr.2017.7610].

Hiker, a new family of DNA transposons encoding transposases with DD35E motifs, displays a distinct phylogenetic relationship with most known DNA transposon families of IS630-Tc1-mariner (ITm).

DNA transposons play a crucial role in determining the size and structure of eukaryotic genomes. In this study, a new family of IS630-Tc1-mariner (ITm) DNA transposons, named Hiker (HK), was identified. HK is characterized by a DD35E catalytic domain and is distinct from all previously known families of the ITm group. Phylogenetic analyses showed that DD35E/Hiker forms a monophyletic clade with DD34E/Gambol, indicating that they may represent a separate superfamily of ITm. A total of 178 Hiker species were identified, with 170 found mainly in Actinopterygii, one in Chondrichthyes, six in Anura and one in Mollusca. Gambol (GM), on the other hand, are found in invertebrates, with 18 in Arthropoda and one in Platyhelminthes. Hiker transposons have a total length ranging from 2.14 to 3.67 kb and contain a single open reading frame that encodes a protein of approximately 370 amino acids (range 311-413 aa). They are flanked by short terminal inverted repeats (TIRs) of 16-30 base pairs and two base pair (TA) target-site duplications. In contrast, most transposons of the Gambol family have a total length of 1.35-5.96 kb, encode a transposase protein of approximately 350 amino acids (range 306-374 aa), and are flanked by TIRs that range from 32 to 1097 bp in length. Both Hiker and Gambol transposases have several conserved motifs, including helix-turn-helix (HTH) motifs and a DDE domain. Our study observed multiple amplification waves and repeated horizontal transfer (HT) events of HK transposons in vertebrate genomes, indicating their role in diversifying and shaping the genomes of Actinopterygii, Chondrichthyes, and Anura. Conversely, GM transposons showed few Horizontal transfer events. According to cell-based transposition assays, most HK transposons are likely inactive due to the truncated DNA binding domains of their transposases. We present an updated classification of the ITm group based on these findings, which will enhance the understanding of both the evolution of ITm transposons and that of their hosts.

Mosquito (MS), a DD37E Family of Tc1/Mariner, Displaying a Distinct Evolution Profile from DD37E/TRT and DD37E/L18.

Diverse Tc1/mariner elements with the DD37E signature have been detected. However, their evolutionary relationship and profiles are largely unknown. Using bioinformatics methods, we defined the evolution profile of a Tc1/Mariner family, which harbors the catalytic domain with the DD37E signature, and renamed it DD37E/Mosquito (MS). MS transposons form a separate monophyletic clade in the phylogenetic tree, distinct from the other two groups of elements with the DD37E signature, DD37E/L18 and DD37E/TRT (transposon related to Tc1), and represent a very different taxonomic distribution from that of DD37E/TRT. MS is only detected in invertebrate and is mostly present in Arthropoda, as well as in Cnidaria, Ctenophora, Mollusca, Nematoda, and Platyhelminthes, with a total length of about 1.3 kb, containing an open reading frame (ORF) encoding about 340 amino acids transposases, with a conserved DD37E catalytic domain. The terminal inverted repeat (TIR) lengths range from 19 bp to 203 bp, and the target site duplication (TSD) is TA. We also identified few occurrences of MS horizontal transfers (HT) across lineages of diptera. In this paper, the distribution characteristics, structural characteristics, phylogenetic evolution, and horizontal transfer of the MS family are fully analyzed, which is conducive to supplementing and improving the Tc1/Mariner superfamily and excavating active transposons.

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial.

BACKGROUND: The aim of this study was to investigate the antitumour activity, safety, and tolerability of pamiparib plus tislelizumab in patients with previously treated advanced solid tumours. METHODS: In this study, patients were enrolled into eight arms by tumour type. All received pamiparib 40 mg orally twice daily plus tislelizumab 200 mg intravenously every 3 weeks. The primary endpoint was objective response rate (ORR), assessed by the investigator per Response Evaluation Criteria in Solid Tumours v1.1. Secondary endpoints included duration of response (DoR), safety, and tolerability. RESULTS: Overall, 180 patients were enrolled. In the overall population, the ORR was 20.0% (range: 0-47.4 across study arms), with median DoR of 17.1 months (95% confidence interval [CI]: 6.2, not estimable [NE]). The highest ORR was observed in the triple-negative breast cancer (TNBC) arm (patients with BRCA1/2 mutations and/or homologous recombination deficiency) (ORR: 47.4%; median DoR: 17.1 months [95% CI: 3.0, NE]). Treatment-emergent adverse events (TEAEs) of ≥Grade 3 occurred in 61.7% of patients. Serious TEAEs occurred in 50.0% of patients. CONCLUSIONS: Pamiparib plus tislelizumab showed a variable level of antitumour activity in patients with advanced solid tumours, with the highest ORR in TNBC and was associated with a manageable safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov: NCT02660034.