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The non-neural cholinergic system plays a critical role in regulating immune equilibrium and tissue homeostasis. While the expression of choline acetyltransferase (ChAT), the enzyme catalyzing acetylcholine biosynthesis, has been well documented in lymphocytes, its role in the myeloid compartment is less understood. Here, we identify a significant population of macrophages (Mϕs) expressing ChAT and synthesizing acetylcholine in the resolution phase of acute peritonitis. Using Chat -GFP reporter mice, we observed marked upregulation of ChAT in monocyte-derived small peritoneal Mϕs (SmPMs) in response to Toll-like receptor agonists and bacterial infections. These SmPMs, phenotypically and transcriptionally distinct from tissue-resident large peritoneal macrophages, up-regulated ChAT expression through a MyD88-dependent pathway involving MAPK signaling. Notably, this process was attenuated by the TRIF-dependent TLR signaling pathway, and our tests with a range of neurotransmitters and cytokines failed to induce a similar response. Functionally, Chat deficiency in Mϕs led to significantly decreased peritoneal acetylcholine levels, reduced efferocytosis of apoptotic neutrophils, and a delayed resolution of peritonitis, which were reversible with exogenous ACh supplementation. Intriguingly, despite B lymphocytes being a notable ChAT-expressing population within the peritoneal cavity, Chat deletion in B cells did not significantly alter the resolution process. Collectively, these findings underscore the crucial role of Mϕ-derived acetylcholine in the resolution of inflammation and highlight the importance of the non-neuronal cholinergic system in immune regulation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Introduction of the trifluoromethyl (CF 3 ) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine-mediated radical process for C(sp 2 )-H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to >20 : 1), and broad functional group compatibility. Expansion of this approach to perfluoroalkylation and late-stage trifluoromethylation of bioactive molecules demonstrates its promising application potential. Mechanistic studies suggest that the reaction follows a radical addition and subsequent elimination pathway., (© 2024 Wiley-VCH GmbH.)

Background: Recently, type 2 diabetic osteoporosis (T2DOP) has become a research hotspot for the complications of diabetes, but the specific mechanism of its occurrence and development remains unknown. Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP. Polycytosine RNA-binding protein 1 (PCBP1), an iron ion chaperone, is considered a protector of ferroptosis., Aim: To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes., Methods: A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose (HG) and/or ferroptosis inhibitors at different concentrations and times. Transmission electron microscopy was used to examine the morphological changes in the mitochondria of osteoblasts under HG, and western blotting was used to detect the expression levels of PCBP1, ferritin, and the ferroptosis-related protein glutathione peroxidase 4 (GPX4). A lentivirus silenced and overexpressed PCBP1. Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin (OPG) and osteocalcin (OCN), whereas flow cytometry was used to detect changes in reactive oxygen species (ROS) levels in each group., Results: Under HG, the viability of osteoblasts was considerably decreased, the number of mitochondria undergoing atrophy was considerably increased, PCBP1 and ferritin expression levels were increased, and GPX4 expression was decreased. Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1, increased the expression levels of ferritin, GPX4, OPG, and OCN, compared with the HG group. Flow cytometry results showed a reduction in ROS, and an opposite result was obtained after silencing PCBP1., Conclusion: PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment. Moreover, PCBP1 may be a potential therapeutic target for T2DOP., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The third species of the small and rare stag beetle genus Capreolucanus Didier, 1928 was found from Yunnan Province, China: C. yanxui Qi & Zhou, new species. The complete mitogenome of the new species is assembled. Based on morphological characters and the mitochondrial marker COX1, the new species can be clearly distinguished from C. sicardi Didier, 1928, the most similar species. A key is provided to distinguish all known species of this genus and some new genetic and biological information of the genus are reported for the first time.

Background: Chrysochroinae Laporte de Castelnau, 1835 is the very colourful subfamily of Buprestidae. There are 127 species and subspecies of the subfamily which have been recorded in China., New Information: In this paper, we reported three genera, two subgenera and five species of the subfamily Chrysochroinae Laporte de Castelnau, 1835 (Coleoptera, Buprestidae) which are all newly recorded from China. These reported taxa belong to two tribes and four genera: Chrysochroa (Chroodema) corbetti (Kerremans, 1893), Chrysochroa (Pyranthe) fulgens ephippigera White, 1843, Demochroa (Demoxantha) gratiosa indica Csiki, 1900, Xanthocatabonvouloirii (Deyrolle, 1861) (all the above four being Chrysochroini) and Cardiaspismouhotii E. Saunders, 1866 (Dicercini). The five newly-recorded species are briefly described, illustrated and supplemented with relevant biological information., (Hong-Mu Ai, Zhi-Hao Qi, Rong-Xiang Su, Zhi-Yu Liao, Hai-Tian Song.)

Lenvatinib is a multitargeted tyrosine kinase inhibitor capable of promoting apoptosis, suppressing angiogenesis, inhibiting tumor cell proliferation, and modulating the immune response. In multiple cancer types, lenvatinib has presented manageable safety and is currently approved as an effective first-line therapy. However, with the gradual increase in lenvatinib application, the inevitable progression of resistance to lenvatinib is becoming more prevalent. A series of recent researches have reported the mechanisms underlying the development of lenvatinib resistance in tumor therapy, which are related to the regulation of cell death or proliferation, histological transformation, metabolism, transport processes, and epigenetics. In this review, we aim to outline recent discoveries achieved in terms of the mechanisms and potential predictive biomarkers of lenvatinib resistance as well as to summarize untapped approaches available for improving the therapeutic efficacy of lenvatinib in patients with various types of cancers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this paper, two new species of Buprestis subgenus Akiyamaia Kurosawa, 1988 are described: B. (A.) gengmini Qi & Song, new species from Yunnan Province, China and B. (A.) wenii Qi & Song, new species from Yen Bai Province, Vietnam. The descriptions and illustrations of two new species are provided, and the diagnostic characters are provided to distinguish the two new species from other related species. A key is given for identification of all Akiyamaia species.The holotype of B. (A.) costipennis (Fairmaire, 1891) and pictures of living individuals are illustrated for the first time.

Extracellular deposition of β-amyloid (Aβ) and intracellular hyperphosphorylated tau are the predominant pathological changes in Alzheimer's disease (AD). Increasing evidence demonstrates a critical role of a variety of small GTPases, namely Ras-related proteins (Rabs), in the pathogenesis of AD. As crucial regulators of intracellular membrane trafficking, alteration in Rab protein expression and function represents one of the primary factors contributing to the abnormal membrane trafficking in AD. Additionally, the Rab GTPases are also involved in the development of Aβ, tau and other pathological changes associated with AD. In this article, we conduct a comprehensive review on the primary functions of multiple Rab proteins and their involvement in the pathogenesis of AD.

A new species Coomaniella sunfengyii Liao, Su, Qi & Song, sp. nov. from Fujian Province, China, is described and placed in the Coomaniella macropus species-group. The description, illustrations, host plant information and diagnostic characters of the new species are provided.

Many functional materials are approaching their performance limits due to inherent trade-offs between essential physical properties. Such trade-offs can be overcome by engineering a material that has an ordered arrangement of structural units, including constituent components/phases, grains, and domains. By rationally manipulating the ordering with abundant structural units at multiple length scales, the structural ordering opens up unprecedented opportunities to create transformative functional materials, as amplified properties or disruptive functionalities can be realized. In this perspective article, a brief overview of recent advances in the emerging ordered functional materials across catalytic, thermoelectric, and magnetic materials regarding the fabrication, structure, and property is presented. Then the possibility of applying this structural ordering strategy to highly efficient neuromorphic computing devices and durable battery materials is discussed. Finally, remaining scientific challenges are highlighted, and the prospects for ordered functional materials are made. This perspective aims to draw the attention of the scientific community to the emerging ordered functional materials and trigger intense studies on this topic., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

A new stag beetle is described from Yunnan Province, China: Lucanus jiaozishanus Qi, He, Su & Song, new species. It is the third species of the L. boileaui group which are distributed only in Southwestern China and Northeastern Myanmar. The differences of the new species with the more related taxa (L. boileaui Planet, 1897, L. ludivinae Boucher, 1998 and L. takeoi Adachi, 2020) are discussed. A new synonymy, L. bidentis Schenk, 2013 = L. boileaui, is proposed. Keys to males and females of the L. boileaui group are provided. The variation of males, the female and the host plant of L. takeoi (L. maculifemoratus group) are illustrated for the first time.

Background: The genus Cantonius Théry, 1929 is a small group with two subgenera and 12 species. However, the biology of this genus is still unknown., New Information: In this paper, three species of the genus Cantonius Théry, 1929 were found on bamboo leaves, revealing for the first time that Cantonius species are also leaf-miners. Two new species were recorded from Jiangxi Province and are described here: Cantonius (Cantonius) anjiensis sp. n. (host plant: Pleioblastusamarus ) and Cantonius (Procantonius) qiyunensis sp. n. (host plant: Bambusablumeana ) followed by C. (P.) austrisinicus Kalashian, 2021 (host plant: Oligostachyumpaniculatum ) recorded from Guangxi Province. Including habitats, photos of three species together with C. (P.) qiyunensis sp. n. pupa, host plants, and leaf mines of the three species are presented. Moreover, the bionomics and habits of the genus are discussed for the first time, and a hypothesis for the distribution of Cantonius is provided., (Xiao-Di Shi, Zhi-Ming Wu, Xiao-Hua Dai, Jia-Sheng Xu, Hai-Tian Song.)

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

Probabilistic computing has emerged as a viable approach to solve hard optimization problems. Devices with inherent stochasticity can greatly simplify their implementation in electronic hardware. Here, we demonstrate intrinsic stochastic resistance switching controlled via electric fields in perovskite nickelates doped with hydrogen. The ability of hydrogen ions to reside in various metastable configurations in the lattice leads to a distribution of transport gaps. With experimentally characterized p-bits, a shared-synapse p-bit architecture demonstrates highly parallelized and energy-efficient solutions to optimization problems such as integer factorization and Boolean satisfiability. The results introduce perovskite nickelates as scalable potential candidates for probabilistic computing and showcase the potential of light-element dopants in next-generation correlated semiconductors.

Nanoparticle self-assembly enables the generation of complex ordered nanostructures with enhanced properties or new functionalities. However, the ordering is often limited to the micrometer scale with chemical strategies due to the relative weak supramolecular interactions that govern the self-assembly process. Here a physical strategy via temperature-gradient-assisted self-assembly is reported to create three-dimensional (3D) macroscopic ordered nanocomposites with different gradient variations in grain size, constituent content, and crystal orientation. The resulting α-Fe/Pr 2 Fe 14 B ordered nanostructure with reverse gradients in both the grain size and α-Fe content exhibits a record-high energy density of about 25 MGOe for isotropic α-Fe/Pr 2 Fe 14 B systems, approximately 130% higher than that of its disordered counterpart. Both experiments and micromagnetic simulations demonstrate that creating ordered nanostructures is an alternative approach to develop high-performance permanent-magnet materials. Our findings make a significant step toward creating 3D macroscopic ordered nanostructures and will stimulate the development of ordered nanomaterials.

Bone fractures are one of the most common injuries, and they have a big effect on population health worldwide. Traumatic bone injuries can be partially treated with implanting bone-graft substitutes, for example, hydroxyapatite (HA), a bioceramic that is similar materially to natural bones with good bioactivity and osteoconductivity. It could, however, be vulnerable to infections because of the way an HA-based bone graft is put in, which could be a weakness in the host's defense. This study incorporated silver (Ag) into hydroxyapatite (Ag-HA) and silicon-containing hydroxyapatite (AgSi-HA) discs to combat this implant-triggered infection. Further, we investigated the antibacterial activities and potential underlying mechanism against a gram-negative bacterium, Pseudomonas aeruginosa. We noticed that the rich calcium (Ca 2+ ) content in HA discs could trigger the change in P. aeruginosa physiology that leads to the enhanced bacterial growth on non‑silver incorporated HA discs. But the released Ag + from Ag-HA and AgSi-HA discs caused significant damage to bacterial cells at a low concentration of 0.3 ppm. We also observed dramatic morphological changes of Ag-HA and AgSi-HA surface-attached bacteria cells. Finally, we identified a potential action mechanism - the surface-bound Ag + from Ag-HA and AgSi-HA potently inhibited the outer membrane protein F (OprF) expression of P. aeruginosa. Collectively, our results indicate that incorporating silver ions into HA could contribute viably to excellent antibacterial activities against P. aeruginosa to prevent HA-based bone graft infection., Competing Interests: Declaration of competing interest The authors declared that there are no personal conflict of interests influencing the work produced in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The genus Chrysodema currently recorded from China contains 6 species/subspecies: C. (Chrysodema) aurostriata Saunders, 1866 from Yunnan, C. (C.) lewisii nakatai Frank Sekerka, 2020, C. (C.) eximia berliozi Descarpentries, 1948, C. (Pseudochrysodema) dalmanni dalmanni (Mannerheim, 1837), C. (P.) dalmanni penghuensis Hattori Ong, 2020 and C. (P.) yasumatsui Kurosawa, 1954 all from Taiwan. In this study, one new species, Chrysodema (Chrysodema) hainanensis sp. nov. from Hainan Island, China is described, illustrated, and the variation is given. The host plant Toona ciliata is new for the genus Chrysodema. The differences of the new species to its related species and subspecies are discussed and keyed. C. (C.) aurostriata from Yunnan probably belonged toC. (C.)vrabeci and still need verification. C. (C.) tonkinea Kerremans, 1909 was recorded from Guangxi (new country record). All Chrysodema species and subspecies recorded from China except C. (P.) dalmanni penghuensis and the unverified C. (C.) aurostriata were examined, and a key is given for identification.

Reconfigurable devices offer the ability to program electronic circuits on demand. In this work, we demonstrated on-demand creation of artificial neurons, synapses, and memory capacitors in post-fabricated perovskite NdNiO 3 devices that can be simply reconfigured for a specific purpose by single-shot electric pulses. The sensitivity of electronic properties of perovskite nickelates to the local distribution of hydrogen ions enabled these results. With experimental data from our memory capacitors, simulation results of a reservoir computing framework showed excellent performance for tasks such as digit recognition and classification of electrocardiogram heartbeat activity. Using our reconfigurable artificial neurons and synapses, simulated dynamic networks outperformed static networks for incremental learning scenarios. The ability to fashion the building blocks of brain-inspired computers on demand opens up new directions in adaptive networks.

Background: This study aimed to investigate fetal and maternal outcomes in women with active lupus nephritis (LN). Specifically, we compared women who had new-onset LN and those with pre-existing LN during pregnancy., Methods: Patients with active LN during pregnancy were divided into the new-onset group (LN first occurred during pregnancy) and the pre-existing group (a history of LN) on the basis of the onset time of LN. Data on clinical features, laboratory findings, and pregnancy outcome were collected and analyzed between the two groups. Multivariate logistic regression analysis was used to compare the effects of active LN on adverse pregnancy outcomes., Results: We studied 73 pregnancies in 69 women between 2010 and 2019. Of these, 38 pregnancies were in the pre-existing LN group and 35 were in the new-onset group. Patients with pre-existing LN had a higher risk of composite adverse fetal outcomes than those with new-onset LN [adjusted odds ratio (ORs), 44.59; 95% confidence interval (CI), 1.21-1664.82; P = 0.039]. However, the two groups had similar adverse maternal outcomes (ORs, 1.24; 95% CI, 0.36-4.29). Serum albumin and proteinuria significantly improved after pregnancy (P < 0.001). Kaplan-Meier analysis showed that the long-term renal outcome was similar between the two groups., Conclusions: Pregnant patients with pre-existing LN were associated with a higher risk of composite adverse fetal outcomes than those with new-onset LN. However, these two groups of patients had similar adverse maternal outcomes. The long-term renal outcomes were not different after pregnancy between these two groups., (© 2021. The Author(s).)

A new genus and species, Termitocnemis huangi gen. et sp. nov., of the tenebrionine tribe Amarygmini Gistel, 1848 is described from Fujian Province, southeastern China. All specimens were collected from a healthy nest of the termite genus Nasutitermes Dudley, 1890, implying that this species is truly termitophilous. Transitional habitus characters of the new species shed further light on the evolution of amarygmine beetles from free-living to termitophily. Given the discovery of this new genus a revised key is provided to the Oriental genera of termitophilous Amarygmini.

A new species, T. yaolihuoi Huang, Jiang Song sp. nov. of the genus Teratozephyrus Sibatani, 1946 is described from southeastern China. Among the other representatives of the genus, the new species resembles only T. hinomaru Fujioka, 1994 from southwestern China, from which the new species can be separated easily by examining details in both wing pattern and the male genitalia. Wing patterns and genitalia of the new species and T. hinomaru are illustrated and compared.

Under stress conditions, hematopoietic stem and progenitor cells (HSPCs) can translate danger signals into a plethora of cytokine signals. These cytokines, or more precisely their combination, instruct HSPCs to modify the magnitude and composition of hematopoietic output in response to the threat, but investigations into the heterogeneous cytokine expression and regulatory mechanisms are hampered by the technical difficulty of measuring cytokine levels in HSPCs at the single-cell level. Here, we optimized a flow cytometry-based method for the simultaneous assessment of multiple intracellular cytokines in HSPCs. By selecting an optimal combination of cytokine restimulation reagents, protein transport inhibitors, and culture supplements, an optimized restimulation protocol for intracellular staining was developed. Using this method, we successfully examined expression levels of granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in murine and human HSPC subsets under steady-state or different stress conditions. Different cytokine expression patterns were observed, suggesting distinct regulatory modes of cytokine production dependent on the HSPC subset, cytokine, disease, organ, and species. Collectively, this technical advance may help to obtain a better understanding of the nature of HSPC heterogeneity on the basis of differential cytokine production., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Luo, Lin, Zhu, Chen, Yang, Li, Liu, Zheng and Wu.)

Solid tumors are often challenged by hypoxic and nutrient-deprived tumor microenvironments (TME) as tumors progress, due to limited perfusion and rapid nutrient consumption. While cancer cells can demonstrate the ability to survive in nutrient-deprived conditions through multiple intrinsic alterations, it is poorly understood how nutrient-deprived cancer cells co-opt the TME to promote cancer cell survival and tumor progression. In the present study, we found that glutamine deprivation markedly potentiated the expression of G-CSF and GM-CSF in mouse mammary cancer cells. The IRE1α-JNK pathway, which is activated by glutamine starvation, was found to be important for the upregulation of these cytokines. G-CSF and GM-CSF are well-known facilitators of myelopoiesis and mobilization of hematopoietic progenitor cells (HPC). Consistently, as tumors progressed, we found that several myeloid HPC compartments were gradually decreased in the bone marrow but were significantly increased in the spleen. Mechanistically, the HPC-maintaining capacity of the bone marrow was significantly impaired in tumor-bearing mice, with lower expression of HPC maintaining genes (i.e., CXCL12, SCF, ANGPT1, and VCAM1), and reduced levels of mesenchymal stem cells and CXCL12-producing cells. Furthermore, the mobilized HPCs that displayed the capacity for myelopoiesis were also found to accumulate in tumor tissue. Tumor-infiltrating HPCs were highly proliferative and served as important sources of immunosuppressive myeloid-derived suppressor cells (MDSCs) in the TME. Our work has identified an important role for glutamine starvation in regulating the expression of G-CSF and GM-CSF, and in facilitating the generation of immunosuppressive MDSCs in breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sun, Wu, Chen, Xu, Yang, Chen, Yu, Wang, Shuang and Zheng.)

Research on erythrocytic Plasmodium vivax merozoite antigens is critical for identifying potential vaccine candidates in reducing P. vivax disease. However, many P. vivax studies are constrained by its inability to undergo long-term culture in vitro Conserved across all Plasmodium spp., merozoite surface proteins are essential for invasion into erythrocytes and highly expressed on erythrocytic merozoites, thus making it an ideal vaccine candidate. In clinical trials, the P. vivax merozoite surface protein 1 (PvMSP1-19) vaccine candidate alone has shown to have limited immunogenicity in patients; hence, we incorporate the highly conserved and immunogenic C terminus of both P. vivax merozoite surface protein 8 (PvMSP8) and PvMSP1-19 to develop a multicomponent chimeric protein rPvMSP8+1 for immunization of mice. The resulted chimeric rPvMSP8+1 antibody was shown to recognize native protein MSP8 and MSP1-19 of mature P. vivax schizonts. In the immunized mice, an elevated antibody response was observed in the rPvMSP8+1-immunized group compared to that immunized with single-antigen components. In addition, we examined the growth inhibition of these antibodies against Plasmodium cynomolgi (Berok strain) parasites, which is phylogenetically close to P. vivax and sustains long-term culture in vitro Similarly, the chimeric anti-rPvMSP8+1 antibodies recognize P. cynomolgi MSP8 and MSP1-19 on mature schizonts and showed strong inhibition in vitro via growth inhibition assay. This study provides support for a new multiantigen-based paradigm rPvMSP8+1 to explore potential chimeric vaccine candidates against P. vivax malaria using sister species P. cynomolgi ., (Copyright © 2021 American Society for Microbiology.)

A new species Coomaniella (Coomaniella) dentata sp. nov. from Guangxi Province, China, is described and placed in the C. (C.) chinensis species-group. The variability is discussed, and a new adult host plant is recorded. New distributional records are given for C. biformissima Jendek & Kalashian, 1999 and C. lingafelteri Jendek & Pham, 2013., (Hai-Tian Song.)

Overcoming local immunosuppression is critical for immunotherapy to produce robust anti-tumor responses. Myeloid-derived suppressor cells (MDSCs) are key regulators of immunosuppressive networks and promote tumor progression. However, it remains unclear whether and how tumor-infiltrating MDSCs are shaped in response to anti-PD-1 treatment and what their impact on therapeutic efficacy is in colorectal cancer (CRC). In this study, the levels of infiltrating MDSCs were significantly higher in the non-responding organoids and were selectively reduced in the responding group, with MDSCs showing increased apoptosis and attenuated functional activity after anti-PD-1 treatment. A negative correlation between T-cell activation and MDSC function was also observed in fresh human CRC tissues. Mechanistic studies revealed that autocrine IFN-α/β upregulated TRAIL expression on activated T cells to elicit MDSC apoptosis via the TRAIL-DR5 interaction and acted synergistically with TNF-α to inhibit MDSC function of suppressing the T-cell response through the JNK-NMDAR-ARG-1 pathway. Moreover, blockade of IFN-α/β and TNF-α abolished the therapeutic efficacy of anti-PD-1 treatment by preserving the frequency and suppressive activity of infiltrating MDSCs in a CRC mouse model. This result suggested that reprogramming MDSCs by IFN-α/β and TNF-α from activated T cells was necessary for successful anti-PD-1 treatment and might serve as a novel strategy to improve the response and efficacy of anticancer therapy.

Metabolism is reprogrammed in cancer to fulfill the demands of malignant cells for cancer initiation and progression. Apart from its effects within cancer cells, little is known about whether and how reprogramed metabolism regulates the surrounding tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSC) are key regulators of the TME and greatly affect tumor progression and therapeutic responses. In this study, our results revealed that retinol metabolism-related genes and enzymes were significantly downregulated in human colorectal cancer compared with adjacent colonic tissues, and tumors exhibited a defect in retinoic acid (RA) synthesis. Reduced ADH1-mediated retinol metabolism was associated with attenuated RA signaling and accumulated MDSCs in colorectal cancer tumors. Using an in vitro model, generating MDSCs from CD34 + myeloid precursors, we found that exogenous RA could abrogate the generation of polymorphonuclear MDSCs (PMN-MDSC) with negligible impact on myeloid differentiation. Mechanistically, RA could restrain the glycolytic capacity of myeloid cells, which in turn activated the AMP-activated protein kinase (AMPK) pathway, further impairing the suppressive capacity of myeloid cells. Supplementation with RA could significantly delay tumor growth, with reduced arginase-1-expressing myeloid cells and increased CD8 + and granzyme B + T cells in both colitis-associated and implanted MC38 mouse colorectal cancer models. Our results indicated that the defect in ADH1-mediated RA synthesis could provide a possible mechanism that fosters the generation of PMN-MDSCs in colorectal cancer and that restoring RA signaling in the TME could serve as a promising therapeutic strategy to abrogate the generation of PMN-MDSCs., (©2020 American Association for Cancer Research.)

Malaria is a public health concern worldwide, and Togo has proven to be no exception. Effective approaches to provide information on biological insights for disease elimination are therefore a research priority. Local selection on malaria pathogens is due to multiple factors including host immunity. We undertook genome-wide analysis of sequence variation on a sample of 10 Plasmodium falciparum (Pf) clinical isolates from Togo to identify local-specific signals of selection. Paired-end short-read sequences were mapped and aligned onto > 95% of the 3D7 Pf reference genome sequence in high fold coverage. Data on 266 963 single nucleotide polymorphisms were obtained, with average nucleotide diversity π = 1.79 × 10 -3 . Both principal component and neighbor-joining tree analyses showed that the Togo parasites clustered according to their geographic (Africa) origin. In addition, the average genome-wide diversity of Pf from Togo was much higher than that from other African samples. Tajima's D value of the Togo isolates was -0.56, suggesting evidence of directional selection and/or recent population expansion. Against this background, within-population analyses identifying loci of balancing and recent positive selections evidenced that host immunity has been the major selective agent. Importantly, 87 and 296 parasite antigen genes with Tajima's D values > 1 and in the top 1% haplotype scores, respectively, include a significant representation of membrane proteins at the merozoite stage that invaded red blood cells (RBCs) and parasitized RBCs surface proteins that play roles in immunoevasion, adhesion, or rosetting. This is consistent with expectations that elevated signals of selection due to allele-specific acquired immunity are likely to operate on antigenic targets. Collectively, our data suggest a recent expansion of Pf population in Togo and evidence strong host immune selection on membrane/surface antigens reflected in signals of balancing/positive selection of important gene loci. Findings from this study provide a fundamental basis to engage studies for effective malaria control in Togo., (Copyright © 2020 Kassegne, Komi Koukoura, Shen, Chen, Fu, Chen, Zhou, Chen and Cheng.)

The interactions between light and plasmonic charge oscillations in conducting materials are important venues for realizing nanoscale light manipulations. Conventional metal-based plasmonic devices lack tunability due to the fixed material permittivities. Here, we show that reconfigurable plasmonic functionalities can be achieved using the spatially controlled phase transitions in strongly correlated oxide films. The experimental results discussed here are enabled by a recently developed scanning probe-based technique that allows a nonvolatile, monoclinic-metal VO 2 phase to be reversibly patterned at the nanoscale in ambient conditions. Using this technique, rewritable waveguides, spatially modulated plasmonic resonators, and reconfigurable wire-grid polarizers are successfully demonstrated. These structures, effectively controlling infrared lights through spatially confined mobile carriers, showcase a great potential for building programmable nanoplasmonic devices on correlated oxide platforms.

Oomyzus spiraculus Song, Fei & Cao sp. nov. (Hymenoptera, Eulophidae) is described and illustrated as a gregarious larval-pupal endoparasitoid of Coccinella septempunctata L. (Coleoptera, Coccinellidae). Differentiation between O. spiraculus and its similar species is discussed and a key to differentiate the female and male of these species is provided. DNA barcodes of O. spiraculus and O. scaposus are analyzed and compared., (Hai-Tian Song, Ming-Hui Fei, Bao-Ping Li, Chao-Dong Zhu, Huan-Xi Cao.)

Trees are used by animals, humans and machines to classify information and make decisions. Natural tree structures displayed by synapses of the brain involves potentiation and depression capable of branching and is essential for survival and learning. Demonstration of such features in synthetic matter is challenging due to the need to host a complex energy landscape capable of learning, memory and electrical interrogation. We report experimental realization of tree-like conductance states at room temperature in strongly correlated perovskite nickelates by modulating proton distribution under high speed electric pulses. This demonstration represents physical realization of ultrametric trees, a concept from number theory applied to the study of spin glasses in physics that inspired early neural network theory dating almost forty years ago. We apply the tree-like memory features in spiking neural networks to demonstrate high fidelity object recognition, and in future can open new directions for neuromorphic computing and artificial intelligence.

Tumor-associated myeloid cells are one of the prominent components of solid tumors, serving as major immune regulators for the tumor microenvironment (TME) and an obstacle for immune-checkpoint blocking (ICB) therapy. However, it remains unclear how metabolic processes regulate the generation of suppressive myeloid cells in the TME. Here, we found that hematopoietic precursor cells are enriched in the tissues of several types of human cancer and can differentiate into immature myeloid cells (IMC). Tumor-infiltrating IMCs are highly immunosuppressive, glycolytic, and proliferative, as indicated by high levels of M-CSFR, Glut1, and Ki67. To elucidate the role of metabolism in regulating the generation of IMCs, we induced suppressive IMCs from hematopoietic precursor cells with GM-CSF and G-CSF in vitro We found that the generation of suppressive IMCs was accompanied by increased glycolysis, but not affected by glucose deprivation due to alternative catabolism. Generation of IMCs relied on glutaminolysis, regardless of glucose availability. Glutamine metabolism not only supported the expansion of IMCs with glutamine-derived α-ketoglutarate but also regulated the suppressive capacity through the glutamate-NMDA receptor axis. Moreover, inhibition of glutaminase GLS1 enhanced the therapeutic efficacy of anti-PD-L1 treatment, with reduced arginase 1 + myeloid cells, increased CD8 + , IFNγ + and granzyme B + T cells, and delayed tumor growth in an ICB-resistant mouse model. Our work identified a novel regulatory mechanism of glutamine metabolism in controlling the generation of suppressive IMCs in the TME., (©2019 American Association for Cancer Research.)

Emerging evidence demonstrates that a c-Met antibody-drug conjugate (ADC) has superior efficacy and safety profiles compared with those of currently available small molecules or antibody inhibitors for the treatment of c-Met-overexpressing cancers. Here we described both the in vitro and in vivo efficacies of SHR-A1403, a novel c-Met ADC composed of a humanized IgG2 monoclonal antibody against c-Met conjugated to a novel cytotoxic microtubule inhibitor. SHR-A1403 showed high affinity to c-Met proteins derived from human or monkey and potent inhibitory effects in cancer cell lines with high c-Met protein expression. In mice bearing tumors derived from cancer cell lines or patient HCC tissues with confirmed c-Met overexpression, SHR-A1403 showed excellent anti-tumor efficacy. Antibody binding with c-Met contributed to SHR-A1403 endocytosis; the subsequent translocation to lysosomes and cytotoxicity of the released toxin are speculated to be predominant mechanisms underlying the anti-tumor activity of SHR-A1403. In conclusion, SHR-A1403 showed significant anti-tumor activity in cancer cell lines, xenograft mouse models and an HCC PDX model, which all have high c-Met levels. These data provide references for SHR-A1403 as a potential therapy for the treatment of cancers with c-Met overexpression.

In this work, a novel synthetic strategy for separation media which quickly specific recognize anthocyanins was developed by dummy molecular imprinting technology and magnetic separation technology. Rutin, similar to cyanidin-3-O-rutinoside structure, was selected as a virtual template. The appropriate molecular imprinting system was selected by NIP library screening method, 4-vinyl pyridine and acetonitrile as functional monomer and solvent respectively. The molecularly imprinted layer was formed on the surface of the magnetic carrier to prepare dummy magnetic molecularly imprinted polymers. The microstructures of prepared composites were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA) and X-ray diffraction (XRD). Adsorption kinetics, isothermal adsorption curves and selective specificity were investigated to further reveal the specific recognition mechanism of the adsorbents on anthocyanins. The dummy molecularly imprinted polymers showed a short kinetic equilibrium time, high selectivity (comparing with quercetin and naringin), and satisfying adsorption capacity for anthocyanins. The binding capacity and the imprinting factor of dummy molecularly imprinted polymers can reach 15.69 mg g -1 and 2.05, respectively. In addition, the purity of cyanidin-3-O-rutinoside in the crude extract from Lonicera caerulea increased to 89% after the adsorption of dummy magnetic molecular imprinted polymers. Many favorable capabilities of the prepared molecularly imprinted polymers also provided the basis for further application for separation and purification of anthocyanins in the future., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The precise control of individual components in multicomponent nanostructures is crucial to realizing their fascinating functionalities for applications in electronics, energy-conversion devices, and biotechnologies. However, this control remains particularly challenging for bulk, multicomponent nanomaterials because the desired structures of the constitute components often conflict. Herein, a strategy is reported for simultaneously controlling the structural properties of the constituent components in bulk multicomponent nanostructures through layered structural design. The power of this approach is illustrated by generating the desired structures of each constituent in a bulk multicomponent nanomaterial (SmCo + FeCo)/NdFeB, which cannot be attained with existing methods. The resulting nanostructure exhibits a record high energy density (31 MGOe) for this class of bulk nanocomposites composed of both hard and soft magnetic materials, with the soft magnetic fraction exceeding 20 wt%. It is anticipated that other properties beyond magnetism, such as the thermoelectric and mechanical properties, can also be tuned by engineering such layered architectures., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mott insulating oxides and their heterostructures have recently been identified as potential photovoltaic materials with favorable absorption properties and an intrinsic built-in electric field that can efficiently separate excited electron-hole pairs. At the same time, they are predicted to overcome the Shockley-Queisser limit due to strong electron-electron interaction present. Despite these premises a high concentration of defects commonly observed in Mott insulating films acting as recombination centers can derogate the photovoltaic conversion efficiency. With use of the self-regulated growth kinetics in hybrid molecular beam epitaxy, this obstacle can be overcome. High-quality, stoichiometric LaVO 3 films were grown with defect densities of in-gap states up to 2 orders of magnitude lower compared to the films in the literature, and a factor of 3 lower than LaVO 3 bulk single crystals. Photoconductivity measurements revealed a significant photoresponsivity increase as high as tenfold of stoichiometric LaVO 3 films compared to their nonstoichiometric counterparts. This work marks a critical step toward the realization of high-performance Mott insulator solar cells beyond conventional semiconductors.

Objective: To evaluate the effect and safety of phloroglucinol combined with parecoxib on cystospasm after transurethral resection of the prostate (TURP)., Methods: We conducted a prospective randomized case-control study on 98 patients treated by TURP. After operation, the patients were randomly assigned to a treatment (n=50) and a control group (n=48), the former treated by intravenous injection of 80 mg phloroglucinol qd plus 40 mg parecoxib bid while the latter given 80 mg phloroglucinol only, both for 3 successive days. Then we recorded the frequency and duration of cystospasm, visual analogue scales (VAS), adverse reactions, post-operative bladder irrigation time, catheter-indwelling time, and hospital stay and compared them between the two groups of patients., Results: Compared with the controls, the patients in the treatment group showed a significantly lower frequency of cystospasm (［1.95±0.14］ vs ［0.70±0.65］ times, P<0.01), duration of cystospasm (［0.44±0.21］ vs ［0.12±0.14］ min, P<0.01), and VAS score (2.70±1.80 vs 1.90±1.30, P<0.01) at 48－72 hours after TURP, but no statistically significant differences were found between the control and treatment groups in the post-operative bladder irrigation time (［2.75±0.87］ vs ［2.64±0.83］ d, P>0.05), catheter-indwelling time (［3.52±0.32］ vs ［3.44±0.42］ d, P>0.05), and hospital stay (［5.23±0.81］ vs ［5.10±0.73］ d, P>0.05), and no obvious adverse reactions were observed in either of the two groups., Conclusions: Phloroglucinol combined with parecoxib is more effective and safer than phloroglucinol alone in relieving postoperative cystospasm after TURP.

Objective: To investigate the epidemiological characteristics of measles cases of new genotype D8 in Beijing from January to June, 2013., Methods: Epidemiological survey and descriptive analysis was conducted., Results: 661 suspected measles were reported from January to June, 2013. 416 were confirmed measles cases by serology and etiology detection. 28 measles cases were caused by genotype D8 measles virus by genotype identification. There were 2 measles outbreak including 14 cases and 14 sporadic cases. The incidence peak was during April and May. 25 cases (89.3%, 25/28) occurred in downtown and suburban districts. 22 cases (78.5%, 22/28) were adults aged 15-39 years and 19 cases (67.9%, 19/28) were migrant population. 12 cases (85.7%, 12/14) in outbreak were migrant population working in clothing sales. There was epidemiological association between 2 outbreaks., Conclusion: Measles cases of genotype D8 were found for the first time in Beijing. Genotype D8 virus mainly infected migrant adults and caused local outbreak and endemic.

Objective: To investigate whether no asphyxia neonates with intrauterine distress are complicated with myocardial injury and determine the sensitive biochemical diagnostic parameters., Methods: A total of 89 neonates born in the First Affiliated Hospital of Sun Yat-sen University from July 2009 to December 2009 were enrolled. Fifty-three fetal distress cases with Apgar score > 7 at 1 and 5 minutes were enrolled in the study group; while the rest 36 healthy neonates, whose Apgar score = 10 at 1 and 5 minutes, were the control group. Umbilical artery blood samples of all cases were collected for blood gas analysis and biochemical measurement., Results: (1) pH (7.23 ± 0.07) and BE [(-4.8 ± 3.0) mmol/L] in the study group were significantly lower than pH (7.31 ± 0.03) and BE [(-2.1 ± 1.5) mmol/L ] in the control group(P < 0.05). The lactic acid of study group [(5.2 ± 2.3) mmol/L] was higher than that of the control group [(2.3 ± 1.1) mmol/L], and the difference was significant (P < 0.01). However, there was no significant difference between the two groups in PaO2 [(16.2 ± 7.9) mm Hg (1 mm Hg = 0.133 kPa) vs. (17.5 ± 6.7) mm Hg] and PaCO2 [(54.0 ± 11.2) mm Hg vs. (48.5 ± 5.4) mm Hg; P > 0.05]. (2) The level of CK-MB in neonates with fetal distress[ (48 ± 59) U/L] was significantly higher than that of healthy neonates [(36 ± 27) U/L]. However, no significant difference was found in CK [(194 ± 73) U/L vs. (162 ± 95) U/L] and BNP levels [(519 ± 309) ng/L vs. (481 ± 216) ng/L; P > 0.05]. (3) Spearman rank correlation analysis showed that CK-MB level was negatively correlated with pH (r = -0.296, P < 0.05) and BE (r = -0.318, P < 0.05) of umbilical artery blood, while BNP level was positively correlated with umbilical lactic acid (r = 0.278, P < 0.05). No correlation was found between other parameters (P > 0.05)., Conclusions: Intrauterine distress without neonatal asphyxia had effect on fetal myocardial injury. CK-MB can be used as a sensitive parameter for monitoring the development of myocardial injury. The severity of myocardial injury was related to fetal acidosis.

Fatty acid composition and distribution of human milk fat (HMF), from mothers over different lactating periods in Guangzhou, China, were analyzed. The universal characteristics were consistent with previously reported results although the fatty acid content was within a different range and dependent on the local population (low saturated fatty acid and high oleic acid for Guangdong mothers' milk fat). Based on the composition of the total and sn-2 fatty acids of mature milk fat, an efficient evaluation model was innovatively established by adopting the "deducting score" principle. The model showed good agreement between the scores and the degree of similarity by assessing 15 samples from different sources including four samples of HMF, eight samples of human milk fat substitutes (HMFSs) and infant formulas, and three samples of fats and oils. This study would allow for the devolvement of individual human milk fat substitutes with different and specific fatty acid compositions for local infants.

Objective: To evaluate the influences of abnormal glucose challenge test(GCT) on pregnancy outcomes and neonatal anthropometric data in women with normal oral glucose tolerance test(OGTT)., Methods: Totally 214 women who delivered in the First Affiliated Hospital of Sun Yat-sen University from November 2006 to December 2007 were enrolled. 50 g GCT was performed at 24-28 weeks of gestation and 75 g OGTT would be followed if GCT >/= 7.8 mmol/L. Those patients, whose OGTT results below the following criteria (5.3 mmol/L, 10.0 mmol/L, 8.6 mmol/L, 7.8 mmol/L), were classified as normal OGTT. Altogether, 116 of the 214 women with abnormal GCT and normal OGTT were collected as the study group and the rest 98 women with normal GCT as the control group. The pregnant outcomes of the two groups were analyzed. The neonatal anthropometry, including birth weight, body length, head circumference and shoulder circumference, were recorded. Other neonatal anthropometric data, such as upper arm circumference, tricep skinfold thickness and hypodermic fat thickness of abdomen were measured by a tape measure within 24 hours after birth., Results: (1) Pregnant outcomes: No significant difference was found in the rate of assisted vaginal delivery, polyhydramnios, premature rupture of membranes and fetal distress between the study and control group [10.3% (12/116) vs 4% (4/98), 5.2% (6/116) vs 10% (10/98), 13.8% (16/116) vs 17% (17/98), 20.7% (24/116) vs 13% (13/98), P > 0.05, respectively], but the rate of cesarean section, spontaneous vaginal delivery and large for gestational age babies in the study group were different from those of the control [72.4% (84/116) vs 51% (51/98), 17.2% (20/116) vs 45% (44/98), 25.9% (30/116) vs 6% (6/98), P < 0.05, respectively]. (2) Neonatal anthropometry: The birth weight of the study group was significantly higher than that of the control group [(3.4 +/- 0.4) kg vs (3.3 +/- 0.4) kg, P < 0.05], but no significant difference was shown in any other neonatal anthropometric results between the study and control group, including body length [(49.9 +/- 1.3) cm vs (49.7 +/- 1.4) cm], head circumference [(33.4 +/- 1.5) cm vs (33.8 +/- 1.7) cm], shoulder circumference [(35.4 +/- 2.3) cm vs (35.0 +/- 2.3) cm], upper arm circumference [(11.0 +/- 0.7) cm vs (10.9 +/- 0.8) cm], tricep skinfold thickness [(9.7 +/- 1.0) mm vs (9.9 +/- 1.4) mm] and hypodermic fat thickness of abdomen [(7.2 +/- 1.2) mm vs (7.2 +/- 1.0) mm; all P > 0.05]., Conclusion: Women with abnormal GCT alone may have no significant influences on neonatal anthropometric data, but might have more cesarean section, large for gestational age babies, and neonatal birth weight than those women with normal GCT.

A series of 3-demethoxycarbonyl-3-amide methyl anhydrovinblastine derivatives (5b-24b) was designed, synthesized, and evaluated for their proliferation inhibition activities against two tumor cell lines (A549 and HeLa). Most of the amide anhydrovinblastine derivatives exhibited potent cytotoxicity, with the size of the introduced substituents being the foremost factor in determining the resultant cytotoxic activity. Test results in vivo against sarcoma 180 of three potent compounds (6b, 12b, and 24b) indicated that the introduction of an amide group at the 22-position of anhydrovinblastine (1e) improved both potency and toxicity.

Objective: To detect the mutations of BRCA1 and BRCA2 in sporadic breast cancer and study the relationship between BRCA1 and BRCA2 mutations and breast cancer., Methods: Breast cancer tissues of 144 patients and breast tissues of 30 cases of healthy people who were treated from December 2000 to September 2005 were studied. DNA was extracted by the phenol-chloroform method. Fragments of exon 2, exon 3, exon 5, exon 6, exon 7, exon 8, exon 9, exon 10, exon 11, exon 12, exon 13, exon 14, exon 15, exon 16, exon 17, exon 18, exon 19, exon 20, exon 21, exon 22, exon 23 and exon 24 in the BRCA1 gene and exon 10 and exon 14 in the BRCA2 gene were amplified by polymerase chain reaction. Mutation screening was performed by single-strand conformation polymorphism analysis and alterations were confirmed by DNA sequencing., Results: A total of 20 single nucleotide changes in BRCA1 were detected in the 144 cases of breast cancer patients. The total mutation rate was 13.9% and missense mutation rate was 11.1%. No mutation was detected in the BRCA2 and controls., Conclusions: Mutations in BRCA1 may play an important role in evaluation of sick risk, earlier diagnosis and gene therapy of breast cancer in southern Chinese populations.

A novel technique for detecting low-carbon alcohols in water at microwave frequency is presented. The technique is based on the measurement of microwave scattering parameters of aqueous solutions containing alcohols. The method employs transmission-line technique at frequency field. The scattering parameters were obtained by measuring the microwave transmission power. The changes in scattering parameters were measured when a sample vessel filled with aqueous solution containing low-carbon alcohols was inserted in the microwave transmission line. It is shown, from the experimental data, that there are good linear relationships between the scattering parameters and the concentrations of alcohols within a certain range.

Soy isoflavones have been reported to be natural chemopreventive in several types of human cancer. Daidzein and genistein are two main components of soy isoflavones. In our previous study, they were shown to be anti-proliferative and induce cell cycle arrest at S phase of SHZ-88 rat breast cancer cells. We hypothesized that soy isoflavones might exert its anticancer effect by activating cAMP/PKA pathway. The present study was designed to analyze the effect of soy isoflavones on the cAMP/PKA pathway in SHZ-88 cells. Daidzein and genistein were dissolved in DMSO. Cells were treated with 50 mug/ml daidzein and 15 mug/ml genistein, respectively, and with only equal DMSO in the culture medium as control. The cellular cAMP content was tested by radioimmunoassay (RIA). The activity of adenylate cyclase (AC), phosphodiesterase (PDE) and PKA were measured by RIA and (gamma-(32)P) ATP incorporation. Reverse transcript-polymerase chain reaction (RT-PCR) was used to analyze the expression of cAMP response element binding protein (CREB) mRNA of the cells. The results showed that the concentration of cAMP in the cells treated with 50 mug/ml daidzein and 15 mug/ml genistein was significantly increased by 9.5%and 11.0%, respectively, 5 min later (P<0.05), then increased by 31.0%and 40.3%, respectively, 10 min later (P<0.01), compared with that of the control group cells. The activity of AC was not affected during the course of experiment, but that of PDE was decreased to 71.8%and 71.6%, respectively, in the control group 5 min later (P<0.05). The PKA activity was increased to 125.8%and 122.3%, respectively, in the control group 20 min after the cells were treated with daidzein and genistein (P<0.05), and kept at high level till 40 min after treatment. CREB mRNA of the cells treated with daidzein and genistein was increased by 31.6%and 51.1%, respectively, 3 h later (P<0.05), then began to decrease 6 h after treatment. The current study suggests that soy isoflavones activate the cAMP/PKA pathway in SHZ-88 rat breast cancer cells by inhibiting the activity of phosphodiesterase.