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The genus Carnus Nitzsch, 1818 comprises small ectoparasites that feed on the blood of juvenile avians. They are characterised by dealated adults with setose abdominal intersegmental membranes. Carnus orientalis Maa, 1968 was previously recorded in Malaysia and the Ryukyu Islands of Japan, parasitising two owl species: Ketupa ketupu (Horsfield, 1821) and Otus elegans (Cassin, 1852). This study confirms the occurrence of C. orientalis in Taiwan and presents a new host record, along with COI barcode sequences. Additionally, the study also elucidates the difficulties posed by blood meal contamination and pseudogene amplification as confounding factors intrinsic to the molecular taxonomic delineation of C. orientalis via universal DNA barcoding primers.The following new information regarding C. orientalis is provided in this study:Carnus orientalis is first recorded in Taiwan, filling the gap in its East Asian distribution. This is also the first record of Carnidae from Taiwan.Otus lettia (Hodgson, 1836) (Aves, Strigidae) is reported as a new host for C. orientalis, identified on a fallen fledgling.Co-amplification of the host's COI is reported in this study using the universal PCR primer set LCO1490/HCO2198. Additionally, the amplification of a COI-like pseudogene using a newly-designed primer set is detected through abnormal translated amino acid sequences and the occurrence of a stop codon.New specific primers for the COI gene of Carnus were designed in this study.The new distribution and ecological data of C. orientalis enhance our understanding of this species. The provision of new COI primers is anticipated to contribute to future studies employing DNA barcoding in bird-parasitic flies.

Abstract Flaviviruses strategically utilize the endoplasmic reticulum (ER) in their replication cycles. However, the role of ER autophagy (ER-phagy) in viral replication process remains poorly understood. Here, we reveal that prolonged Zika virus (ZIKV) infection results from the degradation of ER-phagy receptor FAM134B, facilitated by viral NS2A protein. Mechanistically, ER-localized NS2A undergoes K48-linked polyubiquitination at lysine (K) 56 by E3 ligase AMFR. Ubiquitinated NS2A binds to FAM134B and AMFR orchestrates the degradation of NS2A-FAM134B complexes. AMFR-catalyzed NS2A ubiquitination not only targets FAM134B degradation but also hinders the FAM134B-AMFR axis. Notably, a recombinant ZIKV mutant (ZIKV-NS2AK56R), lacking ubiquitination and ER-phagy inhibition, exhibits attenuation in ZIKV-induced microcephalic phenotypes in human brain organoids and replicates less efficiently, resulting in weakened pathogenesis in mouse models. In this work, our mechanistic insights propose that flaviviruses manipulate ER-phagy to modulate ER turnover, driving viral infection. Furthermore, AMFR-mediated flavivirus NS2A ubiquitination emerges as a potential determinant of viral pathogenecity.

Biosensors are a new type of sensor that utilize biologically sensitive materials and microbially active analytes to measure a variety of biological signals. The purpose of monitoring is achieved by combining these sensitive materials with analytes such as proteins, cells, viruses, and bacteria, inducing changes in their physical or chemical properties. The use of nanomaterials in fabricating surface acoustic wave (SAW) biosensors is particularly noteworthy for the label-free detection of organisms due to their compact size, portability, and high sensitivity. Recent advancements in the manufacturing techniques of SAW biosensors have significantly enhanced sensor performance and reliability. These techniques not only ensure precise control over sensor dimensions and material properties but also facilitate scalable and cost-effective production processes. As a result, SAW biosensors are poised to become powerful tools for various clinical and rapid detection applications.

Abstract Positively charged nanofiltration membranes have attracted much attention in the field of lithium extraction from salt lakes due to their excellent ability to separate mono‐ and multi‐valent cations. However, the thicker selective layer and the lower affinity for Li+ result in lower separation efficiency of the membranes. Here, PEI‐P membranes with highly efficient Li+/Mg2+ separation performance are prepared by introducing highly lithophilic 4,7,10‐Trioxygen‐1,13‐tridecanediamine (DCA) on the surface of PEI‐TMC membranes using a post‐modification method. Characterization and experimental results show that the utilization of the DCA‐TMC crosslinked structure as a space‐confined layer to inhibit the diffusion of the monomer not only increases the positive charge density of the membrane but also reduces its thickness by ≈35% and presents a unique coffee‐ring structure, which ensures excellent water permeability and rejection of Mg2+. The ion–dipole interaction of the ether chains with Li+ facilitates Li+ transport and improves the Li+/Mg2+ selectivity (SLi,Mg = 23.3). In a three‐stage nanofiltration process for treating simulated salt lake water, the PEI‐P membrane can reduce the Mg2+/Li+ ratio of the salt lake by 400‐fold and produce Li2CO3 with a purity of more than 99.5%, demonstrating its potential application in lithium extraction from salt lakes.

The rare genus Pseudalomya Telenga comprises two species, which are found only in the Eastern Palaearctic region and high mountains of the Oriental region. The phylogenetic position of Pseudalomya remains unclear because of its intermediate morphology between two ichneumonine tribes, Alomyini and Phaeogenini. This article reports the discovery of a new species of Pseudalomya: Pseudalomya truncaticornis sp. nov. Specimens were collected during a survey of insect fauna in the Dasyueshan area of Shei-Pa National Park, one of the high-altitude regions in Taiwan. The new species can be diagnosed by its body coloration, frontal horn shape, facial punctures, metasomal tergite sculpture, and wing venation. To the best of our knowledge, this is the first record of Pseudalomya in Taiwan. This article also presents a diagnostic key to the global species of Pseudalomya. In this study, molecular phylogenetic analyses were performed using one mitochondrial and two nuclear gene sequences from P. truncaticornis sp. nov. and other members of the Ichneumoniformes group. The results indicate that Pseudalomya should be classified within Phaeogenini, distinct from Alomyini, but more comprehensive phylogenomic studies are needed to confirm this placement.

Abstract Gliomas are the most common primary intracranial tumor worldwide. The maintenance of telomeres serves as an important biomarker of some subtypes of glioma. In order to investigate the biological role of RTEL1 in glioma. Relative telomere length (RTL) and RTEL1 mRNA was explored and regression analysis was performed to further examine the relationship of the RTL and the expression of RTEL1 with clinicopathological characteristics of glioma patients. We observed that high expression of RTEL1 is positively correlated with telomere length in glioma tissue, and serve as a poor prognostic factor in TERT wild-type patients. Further in vitro studies demonstrate that RTEL1 promoted proliferation, formation, migration and invasion ability of glioma cells. In addition, in vivo studies also revealed the oncogene role of RTEL1 in glioma. Further study using RNA sequence and phospho-specific antibody microarray assays identified JNK/ELK1 signaling was up-regulated by RTEL1 in glioma cells through ROS. In conclusion, our results suggested that RTEL1 promotes glioma tumorigenesis through JNK/ELK1 cascade and indicate that RTEL1 may be a prognostic biomarker in gliomas.

Abstract Solar‐driven interfacial evaporation is a promising technology for desalination. The photothermal conversion materials are at the core and play a key role in this field. Design of photothermal conversion materials based on organic dyes for desalination is still a challenge due to lack of efficient guiding strategy. Herein, a new D (donor)‐A (acceptor) type conjugated tetraphenylpyrazine (TPP) luminophore (namely TPP‐2IND) was prepared as a photothermal conversion molecule. It exhibited a broad absorption spectrum and strong π–π stacking in the solid state, resulting in efficient sunlight harvesting and boosting nonradiative decay. TPP‐2IND powder exhibited high photothermal efficiency upon 660 nm laser irradiation (0.9 W cm−2), and the surface temperature can reach to 200°C. Then, an interfacial heating system based on TPP‐2IND is established successfully. The water evaporation rate and the solar‐driven water evaporation efficiency were evaluated up to 1.04 kg m−2 h−1 and 65.8% under 1 sunlight, respectively. Thus, this novel solar‐driven heating system shows high potential for desalination and stimulates the development of advanced photothermal conversion materials.

IntroductionAnimal waste proteins have been increasing in the past decade, along with consumer demands. Their huge volume and the environmental issues caused by improper treatment probably pose a massive threat to human health. These animal waste proteins contain many valuable bioactive peptides and can be used not only as nutrient substances but also as primary functional ingredients in many industries, including agriculture, food, and pharmaceuticals. However, the advancement of the value-added application of animal waste proteins within the past 10 years has not been elucidated yet. In this regard, this paper scrutinized the studies on the applications of hydrolysates and peptides from animal waste proteins throughout the last decade, hoping to display a whole picture of their value-adding applications.MethodsThe Web of Science and Google Scholar were searched from January 1, 2013, to December 12, 2023. This review included field trials, in vitro and in vivo assays, and in silico analysis based on literature surveys or proteolysis simulation. The quality of the included studies was evaluated by Journal Citation Reports, and the rationality of the discussion of studies included.ResultsNumerous studies were performed on the application potential of hydrolysates and peptides of animal waste proteins in agricultural, food, and medicinal industries. Particularly, due to the nutritional value, safety, and especially competitive effects, the peptide with antioxidant, antimicrobial, antihypertensive, antidiabetic, or antithrombotic activities can be used as a primary functional ingredient in food and pharmaceuticals.DiscussionThese value-added applications of animal waste proteins could be a step towards sustainable animal by-products management, and simultaneously, open new avenues in the rapid development of nutraceuticals and pharmaceuticals. However, further studies on the bioavailability and structure-activity relationship are required to verify their therapeutic effects.

Thought to be monotypic for decades, the only species in the goosefish genus Lophiomus Gill, Lm. setigerus (Vahl), shows a wide range of morphological variation and is distributed widely in the Indo-West Pacific (IWP). In this study, datasets for two mitochondrial and two nuclear genes sequences obtained from samples of Lophiomus collected in different localities across the IWP were constructed and analyzed to explore the phylogeny and species diversity within the genus. Our integrated approach with multiline evidence unveiled an unanticipated richness of at least six delimited species of Lophiomus. Herein, based on materials already available from museums and new specimens obtained primarily through the Tropical Deep-Sea Benthos program surveying IWP benthic fauna, we formally describe three new species: Lm. immaculioralis sp. nov., Lm. nigriventris sp. nov., and Lm. carusoi sp. nov. Also, we resurrect Lm. laticeps stat. rev. from synonyms of Lm. setigerus. These species can be diagnosed by genetics, body coloration, patterns on the floor of the mouth, peritoneum pigmentation, morphometric measurements, and meristic counts of cranial spines, dorsal-fin spines, and pectoral-fin and pelvic-fin rays from each other and from Lm. setigerus. The species Lm. setigerus, as well as the genus Lophiomus, are re-described accordingly based on the new results. Amended identification keys to the four extant lophiid genera and to species of Lophiomus are also provided.

The foregut is the main site of lipid absorption in fish, but the effect of different lipid sources on the foregut lipid absorption and metabolism in adult female spotted scat is still unclear. In this experiment, adult female spotted scat (length = 19.48 ± 1.13 cm, weight = 242.83 ± 50.90 g) were fed two iso-nitrogenous (45 % crude protein) and iso-lipidic (12.5 % crude lipid) diets configured with either 8 % fish oil (FO) or 8 % soybean oil (SO) for 60 days. Histological observations, serum measurements and transcriptome sequencing were used to investigate the effects of the oil sources on the foregut. Histological observation showed that the foregut folds of the SO group were shorter and narrower than those of the FO group, and nuclear vacuolation and villous atrophy were observed in the intestinal cells of fish in the SO group, indicating an inflammatory reaction. Both serum triglyceride and total cholesterol levels were significantly higher in the FO group than in the SO group. Transcriptome analysis revealed 1355 differentially expressed genes between the FO and SO groups. Genes related to lipid metabolism (adipor2 and creb3l3) and cholesterol absorption and efflux (npc1l1 and sphk2) were up-regulated, whereas genes related to fatty acid synthesis and transport (fad1 and mfsd2ab) were down-regulated in the FO group. Circadian rhythm related genes ciart and nfil3, which are also involved in lipid metabolism, were up- and down-regulated, respectively in the FO group. The immune-related genes steap4, ddit4 and cldn6 which can inhibit inflammation, were up-regulated in the FO group, whereas pro-inflammation gene rnf225 was up-regulated in the SO group. In conclusion, compared with SO, FO may enhance the lipid absorption and reduce the inflammatory response in the foregut of the spotted scat. The results of this study provide a reference for the selection of dietary oil sources for adult female spotted scat.

Stress granules (SGs), formed by untranslated messenger ribonucleoproteins (mRNPs) during cellular stress in eukaryotes, have been linked to flavivirus interference without clear understanding. This study reveals the role of Zika virus (ZIKV) NS2B as a scaffold protein mediating interaction between protein phosphatase 1α (PP1α) and eukaryotic initiation factor 2α (eIF2α). This interaction promotes eIF2α dephosphorylation by PP1α, inhibiting SG formation. The NS2B-PP1α complex exhibits remarkable stability, resisting ubiquitin-induced degradation and amplifying eIF2α dephosphorylation, thus promoting ZIKV replication. In contrast, the NS2BV35A mutant, interacting exclusively with eIF2α, fails to inhibit SG formation, resulting in reduced viral replication and diminished impact on brain organoid growth. These findings reveal PP1α's dual role in ZIKV infection, inducing interferon production as an antiviral factor and suppressing SG formation as a viral promoter. Moreover, we found that NS2B also serves as a versatile mechanism employed by flaviviruses to counter host antiviral defenses, primarily by broadly inhibiting SG formation. This research advances our comprehension of the complex interplay in flavivirus-host interactions, offering potential for innovative therapeutic strategies against flavivirus infections.

BackgroundAcute promyelocytic leukemia (APL) is rarely caused by the PLZF::RARα fusion gene. While APL patients with PLZF::RARα fusion commonly exhibit diverse hematologic symptoms, the presentation of myeloid sarcoma (MS) as an initial manifestation is infrequent.Case presentationA 61-year-old patient was referred to our hospital with 6-month history of low back pain and difficulty walking. Before this admission, spine magnetic resonance imaging (MRI) conducted at another hospital revealed multiple abnormal signals in the left iliac bone and vertebral bodies spanning the thoracic (T11-T12), lumbar (L1-L4), and sacral (S1/S3) regions. This led to a provisional diagnosis of bone tumors with an unknown cause. On admission, complete blood count (CBC) test and peripheral blood smear revealed a slightly increased counts of monocytes. Immunohistochemical staining of both spinal and bone marrow (BM) biopsy revealed positive expression for CD117, myeloperoxidase (MPO), and lysozyme. BM aspirate showed a significant elevation in the percentage of promyelocytes (21%), which were morphologically characterized by round nuclei and hypergranular cytoplasm. Multiparameter flow cytometry of BM aspirate revealed that blasts were positive for CD13, CD33, CD117, and MPO. Through the integrated application of chromosome analysis, fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), and Sanger sequencing, it was determined that the patient possessed a normal karyotype and a rare cryptic PLZF::RARα fusion gene, confirming the diagnosis of APL.ConclusionIn the present study, we report the clinical features and outcome of a rare APL patient characterized by a cryptic PLZF::RARα fusion and spinal myeloid sarcoma (MS) as the initial presenting symptom. Our study not only offers valuable insights into the heterogeneity of APL clinical manifestations but also emphasizes the crucial need to promptly consider the potential link between APL and MS for ensuring a timely diagnosis and personalized treatments.

Herein, we constructed innovative reduction-sensitive and targeted gelatin-based micelles for doxorubicin (DOX) delivery in tumor therapy. AS1411 aptamer-modified gelatin-ss-tocopherol succinate (AGSST) and the control GSST without AS1411 modification were synthesized and characterized. Antitumor drug DOX-containing AGSST (AGSST-D) and GSST-D nanoparticles were prepared, and their shapes were almost spherical. Reduction-responsive characteristics of DOX release in vitro were revealed in AGSST-D and GSST-D. Compared with non-targeted GSST-D, AGSST-D demonstrated better intracellular uptake and stronger cytotoxicity against nucleolin-overexpressed A549 cells. Importantly, AGSST-D micelles showed more effective killing activity in A549-bearing mice than GSST-D and DOX⋅HCl. It was revealed that AGSST-D micelles had no obvious systemic toxicity. Overall, AGSST micelles would have the potential to be an effective drug carrier for targeted tumor therapy.

Sepsis, a complex clinical syndrome characterized by an exaggerated host response to infection, often necessitates hospitalization and intensive care unit admission. Delayed or inaccurate diagnosis of sepsis, coupled with suboptimal treatment strategies, can result in unfavorable outcomes, including mortality. Maresins, a newly discovered family of lipid mediators synthesized from docosahexaenoic acid by macrophages, have emerged as key players in promoting inflammation resolution and the termination of inflammatory processes. Extensive evidence has unequivocally demonstrated the beneficial effects of maresins in modulating the inflammatory response associated with sepsis; however, their bioactivity and functions exhibit remarkable diversity and complexity. This article presents a comprehensive review of recent research on the role of maresins in sepsis, aiming to enhance our understanding of their effectiveness and elucidate the specific mechanisms underlying their actions in sepsis treatment. Furthermore, emerging insights into the management of patients with sepsis are also highlighted.

In this work, a three-dimensional electrode material (FeN@BC) was prepared by doping iron-nitrogen sites into biochar for activating peroxydisulfate (E-FeN@BC-PS). The scanning electron microscope, x-ray diffractometer, Fourier transform infrared spectroscopy, and x-ray photoelectron spectroscopy results of FeN@BC proved that Fe–N sites were successful doped into BC. Electrochemical analysis indicated that FeN@BC could enhance the electron transfer in the electrochemical process. A significant synergistic effect (SI = 12.46) was observed in the E-FeN@BC-PS system. Tetracycline (TC) was almost removed completely within 30 min in optimal operating parameters. Radical scavenging experiments showed that ·OH, SO4●−, O2●−, and 1O2 all contributed to TC degradation. The cyclic experiment and characterizations before and after the recycle showed that the FeN@BC in the three-dimensional electrode system exhibited excellent stability and reusability, and electricity had an obvious protective effect on the FeN@BC materials. This study revealed the synergistic catalytic mechanism of metal and heteroatomic hybrid materials as three-dimensional electrodes in persulfate activation, promising the development of sustainable and efficient water treatment technology.

Synchronization is a very important phenomenon in the nervous system, which is closely related to the encoding, integration and transmission of information. In this paper, synchronization and transition of a two-compartment respiratory neuron model under transcranial magnetic stimulation (TMS) are studied from the perspective of synchronization degree for the first time. We are established the correlation degree with synchronization, and discussed the firing mode and transition rule of the neurons in the two-compartment compartment pre-Bötzinger complex (PBC) by means of bifurcation theory and Lyapunov index. The results show that the synchronization of neurons has a great influence under TMS, which is embodied in the fact that the somatic will experience a peak firing and a transition from bursting to resting under the magnetic stimulation,which was a phenomenon never before shown in PBC neurons. These results fully reveal the dynamic behavior of PBC nervous system under TMS, and provide theoretical value for further understanding of respiratory rhythm.

Melamine-formaldehyde (MF) tableware is popular in Chinese fast food restaurant and baby feeding. MF product could be hydrolyzed in hot-acid condition and release harmful components. So far, the studies on the hydrolysate and migration of MF products were mainly focused on formaldehyde, melamine and its hydroxy-derivatives. This study presented a deeper analysis for hydrolyzate of 17 MF samples using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). The samples were drilled to powder, then washed and hydrolyzed by diluted hydrochloric acid. An amide column was used for chromatographic separation with amino acetate solution-acetonitrile as mobile phase. Gradient elution was applied with aqueous phase varied from 10% to 30%. The detection was performed by electrospray ion source positive ion (ESI+) and information dependent acquisition (IDA) modes. SCIEX OS software was used for instrument control, data acquisition and processing, in which the “Analytical” module was used to complete the discovery of non-target peaks, and the “Explorer” module was used to achieve manual peak picking and rationality verifying of the deduced chemical structures. 61 components including melamine and 5 MF derivatives, 33 melamine-formaldehyde oligomers and their derivatives, 7 melamine analogues, 6 MF-polyethyleneglycol derivatives, 4 triethanolamine and related compounds, 4 polysacharides were discovered, while some of them were identified for the first time, such as methyl-melamine, methylol substituted methyl-melamine. The possible structure of the components were deduced by relative molecular mass, fragment ions and the synthetic principle of MF. MF derivatives and MF oligomers might generate ［M+H］+ and ［M-H2O+H］+ quasi-molecular ion peaks, while ［M-H2O+H］+ peaks might get higher intensity. Characteristic fragments of melamine-formaldehyde oligomers and their derivatives were m/z 127.07, 139.07, 151.07, 163.07, 169.08, 181.08, 277.14, 289.14, etc. According to the literature, melamine might transform to ammeline, and then to ammelide. In this study, only ammeline was detected. Triethanolamine is an important additive in the synthesis procedure of MF resin to adjust the system acidity. MF-polyethyleneglycol derivatives might be produced from polyethyleneglycol (added for increasing toughness) and MF. 9 components including melamine, MF derivative, MF oligomer, 4 melamine analogues, triethanolamine and triethanolamine derivative were detected in migration solutions of 10 batches of MF tableware under two kinds of acid conditions. The intensity of the detected components was always higer under higher temperature migration condition. Specific migration limit of triethanolamine was 0.05 mg/kg for its hepatic and renal damage toxicity. Other migrated components were submitted to Pub Chem and AMBIT websites for toxicity retrieval and toxicity prediction. Limit toxicity information was found and no toxicity prediction could be deduced by Toxtee method. The research discovers abundant information in hydrolyzate of MF products and supports further toxicological studies and risk assessment.

Nickel-based superalloys have been widely used in the aerospace industry, and regulating the reinforcing phases is the key to improving the high-temperature strength of the alloy. In this study, a series of aging treatments (650 °C, 750 °C, 850 °C and 950 °C for 8 h) were designed to study different thermal deformation behaviors and microstructure evolutions for a novel nickel-based superalloy. Among the aged samples, the 950 °C aged sample achieved the peak stress of ~323 MPa during the thermal deformation and the highest microhardness of ~315 HV after thermal compression, which were the greatest differences compared to before deformation. In addition, the grains of the 950 °C sample exhibit deformed fibrous shapes, and the grain orientation is isotropic, while the other samples exhibited isotropy. In the 850 °C and 950 °C high-temperature aging samples, the γ′ precipitate (about 20 nm in size) is gradually precipitated, which inhibits the movement of dislocation in the grain during compression, thus inhibiting the occurrence of dynamic recrystallization and improving the high-temperature mechanical properties of the alloy.

A thermophilic fungus, named HBFH10, was isolated from Luzhou-flavor Daqu and identified as Rhizopus microsporus. A new β-mannanase gene (RmMan134) from Rhizopus microsporus HBHF10, was cloned using degenerate primers, expressed, and characterized. The cloned RmMan134 gene had a total length of 552 bp without introns, encoding 183 amino acids and one stop codon. The expressed enzyme was composed of one signal peptide sequence of 19 amino acid residues and the catalytic region of the GH134 family. The optimal pH and temperature for the recombinant enzyme were 6.0 and 50 ℃, respectively. It had high thermal and pH stability. Its molecular mass was estimated to be approximately 18.5 kDa, and it was a glycosylated molecule. When konjac gum was used as the substrate, the Km and Vmax values of RmMan134 were 0.66 mg/mL and 57.1 μmol/(min·mg), respectively. RmMan134 exhibited the best clarification efficiency for orange juice, resulting in a 23.8% increase in its clarity, followed apple juice (11%) and peach juice (7%). Moreover, RmMan134 significantly increased the yield of grape juice by about 7%. Overall, RmMan134 has good application prospects in juice processing.

Abstract Solute carrier family 39 member 10 (SLC39A10) belongs to a subfamily of zinc transporters and plays a key role in B-cell development. Previous studies have reported that its upregulation promotes breast cancer metastasis by enhancing the influx of zinc ions (Zn2+); however, its role in gastric cancer remains totally unclear. Here, we found that SLC39A10 expression was frequently increased in gastric adenocarcinomas and that SLC39A10 upregulation was strongly associated with poor patient outcomes; in addition, we identified SLC39A10 as a direct target of c-Myc. Functional studies showed that ectopic expression of SLC39A10 in gastric cancer cells dramatically enhanced the proliferation, colony formation, invasiveness abilities of these gastric cancer cells and tumorigenic potential in nude mice. Conversely, SLC39A10 knockdown inhibited gastric cancer cell proliferation and colony formation. Mechanistically, SLC39A10 exerted its carcinogenic effects by increasing Zn2+ availability and subsequently enhancing the enzyme activity of CK2 (casein kinase 2). As a result, the MAPK/ERK and PI3K/AKT pathways, two major downstream effectors of CK2, were activated, while c-Myc, a downstream target of these two pathways, formed a vicious feedback loop with SLC39A10 to drive the malignant progression of gastric cancer. Taken together, our data demonstrate that SLC39A10 is a functional oncogene in gastric cancer and suggest that targeting CK2 is an alternative therapeutic strategy for gastric cancer patients with high SLC39A10 expression.

Abstract Previous studies disclosed that a high thyroid stimulating hormone level is an independent risk factor for diabetes peripheral neuropathy (DPN) in subclinical hypothyroidism (SCH) patients with type 2 diabetes mellitus (T2DM). However, whether thyroid metabolism has an effect on DPN in euthyroid T2DM patients remains unknown. The aim of this study was to identify the association between thyroid function and DPN in euthyroid T2DM patients. A set of 580 euthyroid T2DM patients was enrolled in the current study and stratified into DPN and Non-DPN groups. Mann–Whitney U test was performed to analyze the continuous variables of biochemical and thyroid metabolism indicators, and the Chi-square test was used to compare the categorical variables. Spearman correlation analysis was performed to analyze the relationship between clinical indicators and free thyroxine (FT4). By using the logistic regression analysis, the prevalence of DPN in different thyroid function indicators were evaluated. T2DM patients with DPN had obviously lower levels of aspartate aminotransferase (AST), alpha-hydroxybutyric dehydrogenase (α-HBDH), superoxide dismutase (SOD), calcium (Ca), creatinine (Cr), uric acid (UA), retinol binding protein (RBP), total protein (TP), albumin (ALB), alanine aminotransferase (ALT) and FT4 than the T2DM patients without DPN (P

Abstract Chemotherapy remains as the first-choice treatment option for triple-negative breast cancer (TNBC). However, the limited tumor penetration and low cellular internalization efficiency of current nanocarrier-based systems impede the access of anticancer drugs to TNBC with dense stroma and thereby greatly restricts clinical therapeutic efficacy, especially for TNBC bone metastasis. In this work, biomimetic head/hollow tail nanorobots were designed through a site-selective superassembly strategy. We show that nanorobots enable efficient remodeling of the dense tumor stromal microenvironments (TSM) for deep tumor penetration. Furthermore, the self-movement ability and spiky head markedly promote interfacial cellular uptake efficacy, transvascular extravasation, and intratumoral penetration. These nanorobots, which integrate deep tumor penetration, active cellular internalization, near-infrared (NIR) light-responsive release, and photothermal therapy capacities into a single nanodevice efficiently suppress tumor growth in a bone metastasis female mouse model of TNBC and also demonstrate potent antitumor efficacy in three different subcutaneous tumor models.

Abstract STAG2, an important subunit in cohesion complex, is involved in the segregation of chromosomes during the late mitosis and the formation of sister chromatids. Mutational inactivation of STAG2 is a major cause of the resistance of BRAF-mutant melanomas to BRAF/MEK inhibitors. In the present study, we found that STAG2 was frequently down-regulated in thyroid cancers compared with control subjects. By a series of in vitro and in vivo studies, we demonstrated that STAG2 knockdown virtually had no effect on malignant phenotypes of BRAF-mutant thyroid cancer cells such as cell proliferation, colony formation and tumorigenic ability in nude mice compared with the control. In addition, unlike melanoma, STAG2 knockdown also did not affect the sensitivity of these cells to MEK inhibitor. However, we surprisingly found that STAG2-knockdown cells exhibited more sensitive to glutamine deprivation or glutaminase inhibitor BPTES compared with control cells. Mechanistically, knocking down STAG2 in BRAF-mutant thyroid cancer cells decreases the protein stability of c-Myc via the ERK/AKT/GSK3β feedback pathway, thereby impairing glutamine metabolism of thyroid cancer cells by down-regulating its downstream targets such as SCL1A5, GLS and GLS2. Our data, taken together, demonstrate that STAG2 inactivation reprograms glutamine metabolism of BRAF-mutant thyroid cancer cells, thereby improving their cellular response to glutaminase inhibitor. This study will provide a potential therapeutic strategy for BRAF-mutant thyroid cancers.

Abstract China has implemented a series of long-term measures to control the spread of COVID-19, however, the effects of these measures on other chronic and acute respiratory infectious diseases remain unclear. Tuberculosis (TB) and scarlet fever (SF) serve as representatives of chronic and acute respiratory infectious diseases, respectively. In China’s Guizhou province, an area with a high prevalence of TB and SF, approximately 40,000 TB cases and hundreds of SF cases are reported annually. To assess the impact of COVID-19 prevention and control on TB and SF in Guizhou, the exponential smoothing method was employed to establish a prediction model for analyzing the influence of COVID-19 prevention and control on the number of TB and SF cases. Additionally, spatial aggregation analysis was utilized to describe spatial changes in TB and SF before and after the COVID-19 outbreak. The parameters of the TB and SF prediction models are R2 = 0.856, BIC = 10.972 and R2 = 0.714, BIC = 5.325, respectively. TB and SF cases declined rapidly at the onset of COVID-19 prevention and control measures, with the number of SF cases decreasing for about 3–6 months and the number of TB cases remaining in decline for 7 months after the 11th month. The spatial aggregation of TB and SF did not change significantly before and after the COVID-19 outbreak but exhibited a marked decrease. These findings suggest that China’s COVID-19 prevention and control measures also reduced the prevalence of TB and SF in Guizhou. These measures may have a long-term positive impact on TB, but a short-term effect on SF. Areas with high TB prevalence may continue to experience a decline due to the implementation of COVID-19 preventive measures in the future.

Abstract Toxoplasma gondii (T. gondii) is an obligate intracellular parasite with a wide range of hosts, including humans and many warm-blooded animals. The parasite exists in two interconvertible forms, namely tachyzoites and bradyzoites in intermediate hosts that are responsible for acute and chronic infections respectively. Mature bradyzoites accumulate large amounts of amylopectin granules but their roles have not been fully characterized. In this study, the predicted key enzymes involved in amylopectin synthesis (UDP-sugar pyrophospharylase, USP) and degradation (alpha-glucan water dikinase, GWD) of ME49 strain were individually knocked out, and then bradyzoite-related phenotyping experiments in vitro and in vivo were performed to dissect their roles during parasite growth and development. Deletion of the usp or gwd gene in the type II strain ME49 reduced the replication rates of tachyzoites in vitro and parasite virulence in vivo, suggesting that amylopectin metabolism is important for optimal tachyzoite growth. Interestingly, the Δusp mutant grew slightly faster than the parental strain under stress conditions that induced bradyzoite transition, which was likely due to the decreased efficiency of bradyzoite formation of the Δusp mutant. Although the Δgwd mutant could convert to bradyzoite robustly in vitro, it was significantly impaired in establishing chronic infection in vivo. Both the Δusp and Δgwd mutants showed a dramatic reduction in the reactivation of chronic infection in an in vitro model. Together, these results suggest that USP and GWD, which are involved in amylopectin synthesis and degradation have important roles in tachyzoite growth, as well as in the formation and reactivation of bradyzoites in T. gondii.

ContextDiabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship between the severity of DR and the pathological severity of diabetic glomerulopathy remains unclear.ObjectiveTo investigate the relationship between severity of diabetic retinopathy (DR) and histological changes and clinical indicators of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM)MethodsPatients with T2DM (n=272) who underwent a renal biopsy were eligible. Severity of DR was classified as non-diabetic retinopathy, non-proliferative retinopathy, and proliferative retinopathy (PDR). Relationship between DN and DR and the diagnostic efficacy of DR for DN were explored.ResultsDN had a higher prevalence of DR (86.4%) and DR was more severe. The sensitivity and specificity of DR in DN were 86.4% and 78.8%, while PDR was 26.4% and 98.5%, respectively. In DN patients, the severity of glomerular lesions (p=0.001) and prevalence of KW nodules (p

Abstract Memristive devices with threshold switching characteristics can be effectively utilized to mimic biological neurons acting as one of the key building blocks for constructing advanced hardware neural networks. In this work, the emulation of leaky integrate‐and‐fire memristive neuron is realized in one single cell with Ag/Ag−In−Zn−S/silk sericin/W architecture without the need for additional auxiliary circuits. The studied devices demonstrate excellent electrical properties, such as stably repeatable threshold switching, concentratedly low threshold voltage (≈0.4 V), and relatively small device‐to‐device variation. In addition, multiple neural features, such as leaky integrate‐and‐fire neuron functionality and strength‐modulated spike frequency characteristic, have been successfully emulated owing to the forming‐free volatile threshold switching effect. The stable volatile threshold switching behaviors and regular firing event may be attributed to the controllable metallic Ag filamentary mechanism. Furthermore, a solid accuracy of 91.44% of the pattern recognition of Modified National Institute of Standards and Technology (MNIST) data is obtained via a trained spiking neural network (SNN) based on the leaky integrate‐and‐fire behavior of sericin‐based device. These achievements shed light on the fact that employing sericin biomaterials has great application potential in advanced neuromorphic computation.

Citizen science is a research approach that involves collaboration between professional scientists and non-professional volunteers. The utilisation of recent online citizen-science platforms (e.g. social networking services) has greatly revolutionised the accessibility of biodiversity data by providing opportunities for connecting professional and citizen scientists worldwide. Meteorus stellatus Fujie, Shimizu & Maeto, 2021 (Hymenoptera, Braconidae, Euphorinae) has been recorded from the Oriental Islands of Japan and known to be a gregarious endoparasitoid of two macro-sized sphingid moths of Macroglossum, Ma. passalus (Drury) and Ma. pyrrhosticta Butler. It constructs characteristic star-shaped communal cocoons, suspended by a long cable. Although M. stellatus has been reported only from the Oriental Islands of Japan, the authors recognise its occurrence and ecological data from Taiwan and the Palaearctic Island of Japan through posts on online citizen-science groups about Taiwanese Insects on Facebook and an article on a Japanese citizen-scientist's website.Through collaboration between professional and citizen scientists via social media (Facebook groups) and websites, the following new biodiversity and ecological data associated with M. stellatus are provided:Meteorus stellatus is recorded for the first time from Taiwan and the Palaearctic Region (Yakushima Is., Japan).Cechetra minor (Butler, 1875), Hippotion celerio (Linnaeus, 1758) and Macroglossum sitiene (Walker, 1856) (Lepidoptera, Sphingidae) are recorded for the first time as hosts of M. stellatus and two of which (C. minor and H. celerio) represent the first genus-level host records for M. stellatus.Mesochorus sp. (Hymenoptera, Ichneumonidae), indeterminate species of Pteromalidae and Trichogrammatidae (Hymenoptera), are recognised as hyperparasitoid wasps of M. stellatus.Parapolybia varia (Fabricius, 1787) (Hymenoptera, Vespidae) is reported as a predator of pendulous communal cocoons of M. stellatus.The nature of suspended large-sized communal cocoons of M. stellatus and the importance and limitations of digital occurrence data and online citizen science are briefly discussed.

Abstract Background Primary immune thrombocytopenia (ITP) is characterized for the skewed Th differentiation towards Th1 and Th17 cells as well as the impaired number and function of regulatory T cells (Tregs). Tregs are capable of co-expressing effector Th markers in different inflammatory milieu, which probably indicates Treg dysfunction and incompetence to counter over-activated immune responses. Methods Ninety-two primary ITP patients from March 2013 to December 2018 were included, and proinflammatory plasticity in different Treg compartments, age groups, and TGFBR2 variant carrier status were investigated. Results Patients were categorized into elderly (n = 44) and younger (n = 48) groups according to an age of 50 years at disease onset. The overall remission rate was 82.6% after first-line regimens, including 47.8% complete remission. TGFBR2 variants were found in 7 (7.6%) patients with three V216I and four T340M heterozygote carriers. ITP patients demonstrated elevated co-expression of IL-17 and decreased co-expression of both IFN-γ and IL-13 than health control (all p

Abstract Introduction Due to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high‐risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands. Methods The multivariate Cox proportional hazards regression was used to select recurrence‐related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT‐PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands. Results In this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence‐free survival (RFS). Then, the recurrence‐related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR = 1.347; 95% CI = 1.012–1.793; p = 0.041), ULBP3 (HR = 0.453; 95% CI = 0.231–0.889; p = 0.021) and ULBP5 (HR = 3.617; 95% CI = 1.819–7.194; p

Lung cancer is a malignancy with high incidence and mortality rates globally, and it has a 5-year survival rate of only 10%–20%. The significant heterogeneity in clinical presentation, histological features, multi-omics findings, and drug sensitivity among different lung cancer patients necessitate the development of personalized treatment strategies. The current precision medicine for lung cancer, primarily based on pathological and genomic multi-omics testing, fails to meet the needs of patients with clinically refractory lung cancer. Lung cancer organoids (LCOs) are derived from tumor cells within tumor tissues and are generated through three-dimensional tissue culture, enabling them to faithfully recapitulate in vivo tumor characteristics and heterogeneity. The establishment of a series of LCOs biobanks offers promising platforms for efficient screening and identification of novel targets for anti-tumor drug discovery. Moreover, LCOs provide supplementary decision-making factors to enhance the current precision medicine for lung cancer, thereby addressing the limitations associated with pathology-guided approaches in managing refractory lung cancer. This article presents a comprehensive review on the construction methods and potential applications of LCOs in both preclinical and clinical research. It highlights the significance of LCOs in biomarker exploration, drug resistance investigation, target identification, clinical precision drug screening, as well as microfluidic technology-based high-throughput drug screening strategies. Additionally, it discusses the current limitations and future prospects of this field.

Background & Aims: Hepatic immune system disorder plays a critical role in the pathogenesis of acute liver injury. The intrinsic signaling mechanisms responsible for dampening excessive activation of liver macrophages are not completely understood. The Notch and Hippo-YAP signaling pathways have been implicated in immune homeostasis. In this study, we investigated the interactive cell signaling networks of Notch1/YAP pathway during acute liver injury. Methods: Myeloid-specific Notch1 knockout (Notch1M-KO) mice and the floxed Notch1 (Notch1FL/FL) mice were subjected to lipopolysaccharide/D-galactosamine toxicity. Some mice were injected via the tail vein with bone marrow–derived macrophages transfected with lentivirus-expressing YAP. Some mice were injected with YAP siRNA using an in vivo mannose-mediated delivery system. Results: We found that the activated Notch1 and YAP signaling in liver macrophages were closely related to lipopolysaccharide/D-galactosamine-induced acute liver injury. Macrophage/neutrophil infiltration, proinflammatory mediators, and hepatocellular apoptosis were markedly ameliorated in Notch1M-KO mice. Importantly, myeloid Notch1 deficiency depressed YAP signaling and facilitated M2 macrophage polarization in the injured liver. Furthermore, YAP overexpression in Notch1M-KO livers exacerbated liver damage and shifted macrophage polarization toward the M1 phenotype. Mechanistically, macrophage Notch1 signaling could transcriptionally activate YAP gene expression. Reciprocally, YAP transcriptionally upregulated the Notch ligand Jagged1 gene expression and was essential for Notch1-mediated macrophage polarization. Finally, dual inhibition of Notch1 and YAP in macrophages further promoted M2 polarization and alleviated liver damage. Conclusions: Our findings underscore a novel molecular insight into the Notch1-YAP circuit for controlling macrophage polarization in acute liver injury, raising the possibility of targeting macrophage Notch1-YAP circuit as an effective strategy for liver inflammation–related diseases.