Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals.

The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.

A solution-processed n-type conducting polymer with ultrahigh conductivity.

Conducting polymers (CPs) with high conductivity and solution processability have made great advances since the pioneering work on doped polyacetylene1-3, thus creating the new field of 'organic synthetic metals,4. Various high-performance CPs have been realized, which enable the applications of several organic electronic devices5,6. Nevertheless, most CPs exhibit hole-dominant (p-type) transport behaviour7,8, whereas the development of n-type analogues lags far behind and only a few exhibit metallic state, typically limited by low doping efficiency and ambient instability. Here we present a facilely synthesized highly conductive n-type polymer poly(benzodifurandione) (PBFDO). The reaction combines oxidative polymerization and in situ reductive n-doping, greatly increasing the doping efficiency, and a doping level of almost 0.9 charges per repeating unit can be achieved. The resultant polymer exhibits a breakthrough conductivity of more than 2,000 S cm-1 with excellent stability and an unexpected solution processability without extra side chains or surfactants. Furthermore, detailed investigations on PBFDO show coherent charge-transport properties and existence of metallic state. The benchmark performances in electrochemical transistors and thermoelectric generators are further demonstrated, thus paving the way for application of the n-type CPs in organic electronics.

Transition metal-catalysed molecular n-doping of organic semiconductors.

Chemical doping is a key process for investigating charge transport in organic semiconductors and improving certain (opto)electronic devices1-9. N(electron)-doping is fundamentally more challenging than p(hole)-doping and typically achieves a very low doping efficiency (η) of less than 10%1,10. An efficient molecular n-dopant should simultaneously exhibit a high reducing power and air stability for broad applicability1,5,6,9,11, which is very challenging. Here we show a general concept of catalysed n-doping of organic semiconductors using air-stable precursor-type molecular dopants. Incorporation of a transition metal (for example, Pt, Au, Pd) as vapour-deposited nanoparticles or solution-processable organometallic complexes (for example, Pd2(dba)3) catalyses the reaction, as assessed by experimental and theoretical evidence, enabling greatly increased η in a much shorter doping time and high electrical conductivities (above 100 S cm-1; ref. 12). This methodology has technological implications for realizing improved semiconductor devices and offers a broad exploration space of ternary systems comprising catalysts, molecular dopants and semiconductors, thus opening new opportunities in n-doping research and applications12, 13.

Origin, loss, and regain of self-incompatibility in angiosperms.

The self-incompatibility (SI) system with the broadest taxonomic distribution in angiosperms is based on multiple S-locus F-box genes (SLFs) tightly linked to an S-RNase termed type-1. Multiple SLFs collaborate to detoxify nonself S-RNases while being unable to detoxify self S-RNases. However, it is unclear how such a system evolved, because in an ancestral system with a single SLF, many nonself S-RNases would not be detoxified, giving low cross-fertilization rates. In addition, how the system has been maintained in the face of whole-genome duplications (WGDs) or lost in other lineages remains unclear. Here we show that SLFs from a broad range of species can detoxify S-RNases from Petunia with a high detoxification probability, suggestive of an ancestral feature enabling cross-fertilization and subsequently modified as additional SLFs evolved. We further show, based on its genomic signatures, that type-1 was likely maintained in many lineages, despite WGD, through deletion of duplicate S-loci. In other lineages, SI was lost either through S-locus deletions or by retaining duplications. Two deletion lineages regained SI through type-2 (Brassicaceae) or type-4 (Primulaceae), and one duplication lineage through type-3 (Papaveraceae) mechanisms. Thus, our results reveal a highly dynamic process behind the origin, maintenance, loss, and regain of SI.

A novel subpopulation of monocytes with a strong interferon signature indicated by SIGLEC-1 is present in patients with in recent-onset type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes is a T cell-mediated autoimmune disease characterised by pancreatic beta cell destruction. In this study, we explored the pathogenic immune responses in initiation of type 1 diabetes and new immunological targets for type 1 diabetes prevention and treatment. METHODS: We obtained peripheral blood samples from four individuals with newly diagnosed latent autoimmune diabetes in adults (LADA) and from four healthy control participants. Single-cell RNA-sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells to uncover transcriptomic profiles of early LADA. Validation was performed through flow cytometry in a cohort comprising 54 LADA, 17 adult-onset type 2 diabetes, and 26 healthy adults, matched using propensity score matching (PSM) based on age and sex. A similar PSM method matched 15 paediatric type 1 diabetes patients with 15 healthy children. Further flow cytometry analysis was performed in both peripheral blood and pancreatic tissues of non-obese diabetic (NOD) mice. Additionally, cell adoptive transfer and clearance assays were performed in NOD mice to explore the role of this monocyte subset in islet inflammation and onset of type 1 diabetes. RESULTS: The scRNA-seq data showed that upregulated genes in peripheral T cells and monocytes from early-onset LADA patients were primarily enriched in the IFN signalling pathway. A new cluster of classical monocytes (cluster 4) was identified, and the proportion of this cluster was significantly increased in individuals with LADA compared with healthy control individuals (11.93% vs 5.93%, p=0.017) and that exhibited a strong IFN signature marked by SIGLEC-1 (encoding sialoadhesin). These SIGLEC-1+ monocytes expressed high levels of genes encoding C-C chemokine receptors 1 or 2, as well as genes for chemoattractants for T cells and natural killer cells. They also showed relatively low levels of genes for co-stimulatory and HLA molecules. Flow cytometry analysis verified the elevated levels of SIGLEC-1+ monocytes in the peripheral blood of participants with LADA and paediatric type 1 diabetes compared with healthy control participants and those with type 2 diabetes. Interestingly, the proportion of SIGLEC-1+ monocytes positively correlated with disease activity and negatively with disease duration in the LADA patients. In NOD mice, the proportion of SIGLEC-1+ monocytes in the peripheral blood was highest at the age of 6 weeks (16.88%), while the peak occurred at 12 weeks in pancreatic tissues (23.65%). Adoptive transfer experiments revealed a significant acceleration in diabetes onset in the SIGLEC-1+ group compared with the SIGLEC-1- or saline control group. CONCLUSIONS/INTERPRETATION: Our study identified a novel group of SIGLEC-1+ monocytes that may serve as an important indicator for early diagnosis, activity assessment and monitoring of therapeutic efficacy in type 1 diabetes, and may also be a novel target for preventing and treating type 1 diabetes. DATA AVAILABILITY: RNA-seq data have been deposited in the GSA human database ( https://ngdc.cncb.ac.cn/gsa-human/ ) under accession number HRA003649.

Robust, Self-Healing, and Multi-Use Poly(Urethane-Urea-Imide) Elastomer as a Durable Adhesive for Thermal Interface Materials.

Currently, research on thermal interface materials (TIMs) is primarily focused on enhancing thermal conductivity. However, strong adhesion and multifunctionality are also important characteristics for TIMs when pursing more stable interface heat conduction. Herein, a novel poly(urethane-urea-imide) (PUUI) elastomer containing abundant dynamic hydrogen bonds network and reversible disulfide linkages is successfully synthesized for application as a TIM matrix. The PUUI can self-adapt to the metal substrate surface at moderate temperatures (80 °C) and demonstrates a high adhesion strength of up to 7.39 MPa on aluminum substrates attributed its noncovalent interactions and strong intrinsic cohesion. Additionally, the PUUI displays efficient self-healing capability, which can restore 94% of its original mechanical properties after self-healing for 6 h at room temperature. Furthermore, PUUI composited with aluminum nitride and liquid metal hybrid fillers demonstrates a high thermal conductivity of 3.87 W m-1 K-1 while maintaining remarkable self-healing capability and adhesion. When used as an adhesive-type TIM, it achieves a low thermal contact resistance of 22.1 mm2 K W-1 at zero pressure, only 16.7% of that of commercial thermal pads. This study is expected to break the current research paradigm of TIMs and offers new insights for the development of advanced, reliable, and sustainable TIMs.

Knocking down a DNA demethylase gene affects potato plant defense against a specialist insect herbivore.

DNA demethylase (DML) is involved in plant development and responses to biotic and abiotic stresses; however, its role in plant-herbivore interaction remains elusive. Here, we found that herbivory by the potato tuber moth, Phthorimaea operculella, rapidly induced the genome-wide DNA methylation and accumulation of DML gene transcripts in potato plants. Herbivory induction of DML transcripts was suppressed in jasmonate-deficient plants, whereas exogenous application of methyl jasmonate (MeJA) improved DML transcripts, indicating that the induction of DML transcripts by herbivory is associated with jasmonate signaling. Moreover, P. operculella larvae grew heavier on DML gene (StDML2) knockdown plants than on wild-type plants, and the decreased biosynthesis of jasmonates in the former may be responsible for this difference, since the larvae feeding on these two genotypes supplemented with MeJA showed similar growth. In addition, P. operculella adult moths preferred to oviposit on StDML2 knockdown plants than on wild-type plants, which was associated with the reduced emission of ß-caryophyllene in the former. In addition, supplementing ß-caryophyllene to these two genotypes further disrupted moths' oviposit choice preference for them. Interestingly, in StDML2 knockdown plants, hypermethylation was found at the promoter regions for the key genes StAOS and StAOC in the jasmonate biosynthetic pathway, as well as for the key gene StTPS12 in ß-caryophyllene production. Our findings suggest that knocking down StDML2 can affect herbivore defense via jasmonate signaling and defense compound production in potato plants.

Transcriptomic and proteomic elucidation of Z chromosome dosage compensation in Helicoverpa armigera.

Transcriptomic data have been used to study sex chromosome dosage compensation (SCDC) in approximately 10 Lepidoptera ZW species, yielding a consensus compensation pattern of Z ≈ ZZ < AA . $$ \approx \mathrm{ZZ}<\mathrm{AA}. $$ It remains unclear whether this compensation pattern holds when examining more Lepidoptera ZW species and/or using proteomic data to analyse SCDC. Here we combined transcriptomic and proteomic data as well as transcriptional level of six individual Z genes to reveal the SCDC pattern in Helicoverpa armigera, a polyphagous lepidopteran pest of economic importance. Transcriptomic analysis showed that the Z chromosome expression of H. armigera was balanced between male and female but substantially reduced relative to autosome expression, exhibiting an SCDC pattern of Z ≈ ZZ < AA $$ \approx \mathrm{ZZ}<\mathrm{AA} $$ . When using H. amigera midgut proteomic data, the SCDC pattern of this species changed from Z ≈ ZZ < AA $$ \approx \mathrm{ZZ}<\mathrm{AA} $$ at transcriptomic level to Z = ZZ = AA at the proteomic level. RT-qPCR analysis of transcript abundance of six Z genes found that compensation for each Z gene could vary from no compensation to overcompensation, depending on the individual genes and tissues tested. These results demonstrate for the first time the existence of a translational compensation mechanism, which is operating in addition to a translational mechanism, such as has been reported in other lepidopteran species. And the transcriptional compensation mechanism functions to accomplish Z chromosome dosage balance between the sexes (M = F on the Z chromosome), whereas the translation compensation mechanism operates to achieve dosage compensation between Z chromosome and autosome (Z = AA).

Heterologous Expression and Characterization of a pH-Stable Chitinase from Micromonospora aurantiaca with a Potential Application in Chitin Degradation.

To promote the bioconversion of marine chitin waste into value-added products, we expressed a novel pH-stable Micromonospora aurantiaca-derived chitinase, MaChi1, in Escherichia coli and subsequently purified, characterized, and evaluated it for its chitin-converting capacity. Our results indicated that MaChi1 is of the glycoside hydrolase (GH) family 18 with a molecular weight of approximately 57 kDa, consisting of a GH18 catalytic domain and a cellulose-binding domain. We recorded its optimal activity at pH 5.0 and 55 °C. It exhibited excellent stability in a wide pH range of 3.0-10.0. Mg2+ (5 mM), and dithiothreitol (10 mM) significantly promoted MaChi1 activity. MaChi1 exhibited broad substrate specificity and hydrolyzed chitin, chitosan, cellulose, soluble starch, and N-acetyl chitooligosaccharides with polymerization degrees ranging from three to six. Moreover, MaChi1 exhibited an endo-type cleavage pattern, and it could efficiently convert colloidal chitin into N-acetyl-D-glucosamine (GlcNAc) and (GlcNAc)2 with yields of 227.2 and 505.9 mg/g chitin, respectively. Its high chitin-degrading capacity and exceptional pH tolerance makes it a promising tool with potential applications in chitin waste treatment and bioactive oligosaccharide production.

Circulating cell-free DNA fragmentation is a stepwise and conserved process linked to apoptosis.

BACKGROUND: Circulating cell-free DNA (cfDNA) is a pool of short DNA fragments mainly released from apoptotic hematopoietic cells. Nevertheless, the precise physiological process governing the DNA fragmentation and molecular profile of cfDNA remains obscure. To dissect the DNA fragmentation process, we use a human leukemia cell line HL60 undergoing apoptosis to analyze the size distribution of DNA fragments by shallow whole-genome sequencing (sWGS). Meanwhile, we also scrutinize the size profile of plasma cfDNA in 901 healthy human subjects and 38 dogs, as well as 438 patients with six common cancer types by sWGS. RESULTS: Distinct size distribution profiles were observed in the HL60 cell pellet and supernatant, suggesting fragmentation is a stepwise process. Meanwhile, C-end preference was seen in both intracellular and extracellular cfDNA fragments. Moreover, the cfDNA profiles are characteristic and conserved across mammals. Compared with healthy subjects, distinct cfDNA profiles with a higher proportion of short fragments and lower C-end preference were found in cancer patients. CONCLUSIONS: Our study provides new insight into fragmentomics of circulating cfDNA processing, which will be useful for early diagnosis of cancer and surveillance during cancer progression.

Dissected Leaf 1 encodes an MYB transcription factor that controls leaf morphology in potato.

KEY MESSAGE: The transcription factor StDL1 regulates dissected leaf formation in potato and the genotype frequency of recessive Stdl1/Stdl1, which results in non-dissected leaves, has increased in cultivated potatoes. Leaf morphology is a key trait of plants, influencing plant architecture, photosynthetic efficiency and yield. Potato (Solanum tuberosum L.), the third most important food crop worldwide, has a diverse leaf morphology. However, despite the recent identification of several genes regulating leaf formation in other plants, few genes involved in potato leaf development have been reported. In this study, we identified an R2R3 MYB transcription factor, Dissected Leaf 1 (StDL1), regulating dissected leaf formation in potato. A naturally occurring allele of this gene, Stdl1, confers non-dissected leaves in young seedlings. Knockout of StDL1 in a diploid potato changes the leaf morphology from dissected to non-dissected. Experiments in N. benthamiana and yeast show that StDL1 is a transcriptional activator. Notably, by calculating the genotype frequency of the Stdl1/Stdl1 in 373-potato accessions, we found that it increases significantly in cultivated potatoes. This work reveals the genetic basis of dissected leaf formation in potato and provides insights into plant leaf morphology.

Microfluidic Investigation of the Ion-Specific Effect on Bubble Coalescence in Salt Solutions.

A microfluidic method was developed to study the ion-specific effect on bubble coalescence in salt solutions. Compared with other reported methods, microfluidics provides a more direct and accurate means of measuring bubble coalescence in salt solutions. We analyzed the coalescence time and approach velocity between bubbles and used simulation to investigate the pressure evolution during the coalescence process. The coalescence time of the three salt solutions decreased initially and then increased as the concentration of the salt solution was increased. The concentration with the shortest coalescence time is considered as the transition concentration (TC) and exhibits ion-specific. At the TC, the change in coalescence time indicates a shift in the effect of salt on bubble coalescence from facilitation to initial inhibition. Meanwhile, it can be seen that the sodium halide solutions significantly inhibit the bubble coalescence and the inhibition capability follows the order NaCl > NaBr > NaI. The results of the approach velocity show that the coalescence time decreases with increasing approach velocity, as well as the approach velocity was strongly influenced by concentration. The approach velocity undergoes a significant change at the TC. Furthermore, simulations of bubble coalescence in the microchannel indicate that the vertical pressure gradient at the center point of the bubble pairs increases as bubbles approach, driving liquid film drainage until bubble coalescence. The pressure at the center of the bubble pair reaches the maximum when the bubbles have first coalesced. It was further revealed that the concentration of the salt solution has a significant impact on the maximum pressure, as evidenced by the observed trend of decreasing pressure values with increasing concentrations.

Oleoylethanolamide ameliorates motor dysfunction through PPARα-mediates oligodendrocyte differentiation and white matter integrity after ischemic stroke.

BACKGROUND AND AIM: Our previous study has revealed that OEA promotes motor function recovery in the chronic stage of ischemic stroke. However, the neuroprotective mechanism of OEA on motor function recovery after stroke still is unexplored. Therefore, the aim of this study was to explore the effects of OEA treatment on angiogenesis, neurogenesis, and white matter repair in the peri-infarct region after cerebral ischemia. EXPERIMENTAL PROCEDURE: The adult male rats were subjected to 2 h of middle cerebral artery occlusion. The rats were treated with 10 and 30 mg/kg OEA or vehicle daily starting from day 2 after ischemia induction until they were sacrificed. KEY RESULTS AND CONCLUSIONS: The results revealed that OEA increased cortical angiogenesis, neural progenitor cells (NPCs) proliferation, migration, and differentiation. OEA treatment enhanced the survival of newborn neurons and oligodendrogenesis, which eventually repaired the cortical neuronal injury and improved motor function after ischemic stroke. Meanwhile, OEA treatment promoted the differentiation of oligodendrocyte progenitor cells (OPCs) and oligodendrogenesis by activating the PPARα signaling pathway. Our results showed that OEA restores motor function by facilitating cortical angiogenesis, neurogenesis, and white matter repair in rats after ischemic stroke. Therefore, we demonstrate that OEA facilitates functional recovery after ischemic stroke and propose the hypothesis that the long-term application of OEA mitigates the disability after stroke.

Multiple Roles of the Stress Sensor GCN2 in Immune Cells.

The serine/threonine-protein kinase general control nonderepressible 2 (GCN2) is a well-known stress sensor that responds to amino acid starvation and other stresses, making it critical to the maintenance of cellular and organismal homeostasis. More than 20 years of research has revealed the molecular structure/complex, inducers/regulators, intracellular signaling pathways and bio-functions of GCN2 in various biological processes, across an organism's lifespan, and in many diseases. Accumulated studies have demonstrated that the GCN2 kinase is also closely involved in the immune system and in various immune-related diseases, such as GCN2 acts as an important regulatory molecule to control macrophage functional polarization and CD4+ T cell subset differentiation. Herein, we comprehensively summarize the biological functions of GCN2 and discuss its roles in the immune system, including innate and adaptive immune cells. We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2's functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.

Sludge biodrying coupled with photocatalysis improves the degradation of extracellular polymeric substances.

The efficiency of sludge dewatering is limited by extracellular polymeric substances (EPS) during biodrying. This study investigated the effect of photocatalysis-mediated EPS degradation on sludge dewatering performance during the sludge biodrying process. The photocatalysis of municipal sludge was first carried out to choose a cost-efficient catalyst. Then sludge biodrying tests were performed using TiO2-coated amendment (TCA) and uncoated amendment (TUCA) as the control. Municipal sludge photocatalysis results showed that using TiO2 could efficiently degrade carbohydrates and proteins in the EPS within 60 min. After 20-day biodrying, photocatalysis significantly promoted a reduction in the moisture content and EPS by 17.64% and 6.88%, respectively. The surface-enhanced Raman scattering (SERS) intensities of the C-C-O symmetric stretching vibration peak of D-lactose and the C-S stretching vibration peak of cysteine were significantly decreased by approximately 33.19% and 44.76%, respectively, indicating that photocatalysis indeed promoted the reduction of polysaccharides and cysteine in the EPS, especially after the thermophilic phase. The hydrophilic amino acid content decreased by 23.02%, verifying that photocatalysis could improve EPS hydrophobicity. Consequently, municipal sludge biodrying coupled with photocatalysis promotes sludge EPS degradation and enhances sludge dewaterability, improving the efficiency of sludge biodrying.

A multi-benefit framework for funding forest management in fire-driven ecosystems across the Western U.S.

Forests across the Western U.S. face unprecedented risk due to historic fire exclusion, environmental degradation, and climate change. Forest management activities like ecological thinning, prescribed burning, and meadow restoration can improve landscape resilience. Resilient forests are at a lower risk of high-intensity wildfires, drought, insects, and other disturbances and provide a wide range of benefits to ecosystems and communities. However, insufficient funding limits implementation of critically needed management. To address this challenge, we propose a multi-benefit framework that leverages the diverse benefits of forest management to engage a suite of stakeholders in sharing project costs. We take a three-pronged approach to develop our conceptual model: examining existing frameworks for environmental project implementation, conducting a literature review of forest management benefits, and evaluating case studies. Through our framework, we describe the steps to engage partners, starting by identifying benefits that could accrue to potential public and private beneficiaries, and moving through an iterative and collaborative process of valuing benefits, which can accrue over different spatial and temporal scales, in close consultation with potential beneficiaries themselves. The aim of this approach is to stack funding streams associated with each valued benefit to fully fund a given forest management project. The multi-benefit framework has the potential to unlock new sources of funding to meet the exceptional challenges of climate and wildfire disturbances. We apply the framework to dry forests of the Western U.S., but opportunities exist for expanding and modifying this approach to any geography or ecosystem where management provides multiple benefits.

n-Type Organic and Polymeric Semiconductors Based on Bithiophene Imide Derivatives.

ConspectusIn the last three decades, p-type (hole-transporting) organic and polymeric semiconductors have achieved great success in terms of materials diversity and device performance, while the development of n-type (electron-transporting) analogues greatly lags behind, which is limited by the scarcity of highly electron-deficient building blocks with compact geometry and good solubility. However, such n-type semiconductors are essential due to the existence of the p-n junction and a complementary metal oxide semiconductor (CMOS)-like circuit in organic electronic devices. Among various electron-deficient building blocks, imide-functionalized arenes, such as naphthalene diimide (NDI) and perylene diimide (PDI), have been proven to be the most promising ones for developing n-type organic and polymeric semiconductors. Nevertheless, phenyl-based NDI and PDI lead to sizable steric hindrance with neighboring (hetero)arenes and a high degree of backbone distortion in the resultant semiconductors, which greatly limits their microstructural ordering and charge transport. To attenuate the steric hindrance associated with NDI and PDI, a novel imide-functionalized heteroarene, bithiophene imide (BTI), was designed; however, the BTI-based semiconductors suffer from high-lying frontier molecular orbital (FMO) energy levels as a result of their electron-rich thiophene framework and monoimide group, which is detrimental to n-type performance.In this Account, we review a series of BTI derivatives developed via various strategies, including ring fusion, thiazole substitution, fluorination, cyanation, and chalcogen substitution, and elaborate the synthesis routes designed to overcome the synthesis challenges due to their high electron deficiency. After structural optimization, these BTI derivatives can not only retain the advantages of good solubility, a planar backbone, and small steric hindrance inherited from BTI but also have greatly suppressed FMO levels. These novel building blocks enable the construction of a great number of n-type organic and polymeric semiconductors, particularly acceptor-acceptor (or all-acceptor)-type polymers, with remarkable performance in various devices, including electron mobility (µe) of 3.71 cm2 V-1 s-1 in organic thin-film transistors (OTFTs), a power conversion efficiency (PCE) of 15.2% in all-polymer solar cells (all-PSCs), a PCE of 20.8% in inverted perovskite solar cells (PVSCs), electrical conductivity (σ) of 0.34 S cm-1 and a power factor (PF) of 1.52 µW m-1 K-2 in self-doped diradicals, and σ of 23.3 S cm-1 and a PF of ∼10 µW m-1 K-2 in molecularly n-doped polymers, all of which are among the best values in each type of device. The structure-property-device performance correlations of these n-type semiconductors are elucidated. The design strategy and synthesis of these novel BTI derivatives provide important information for developing highly electron-deficient building blocks with optimized physicochemical properties. Finally, we offer our insights into the further development of BTI derivatives and semiconductors built from them.

Magnetic Nanoparticles Detection of C-Reactive Protein Combined with Neutrophil to Lymphocyte Ratio to Predict the Occurrence of Anastomotic Fistula after Rectal Cancer Surgery.

It aimed to explore the effect of C-reactive protein (CRP) combined with neutrophil to lymphocyte ratio (NLR) in the early prediction of anastomotic leakage (AL) after rectal cancer surgery and to improve the prediction accuracy. In this study, gold (Au)/ferroferric oxide (Fe3O4) magnetic nanoparticles were first synthesized and modified with polyacrylic acid (PAA). After modification, they underwent CRP antibody detection. Then, 120 patients with rectal cancer who underwent Dixon surgery were selected as the research objects to investigate the sensitivity and specificity of CRP combined with NLR in predicting AL. It was found that the diameter of the Au/Fe3O4 nanoparticles prepared in this study was about 45 nm. After adding 60 µg of antibody, the diameter of PAA-Au/Fe3O4 was 226.5 nm, the dispersion coefficient was 0.16, the standard curve between CRP concentration and luminous intensity was y = 8,966.5 x + 2,381.3, and R2 = 0.9944. Besides, the correlation coefficient was R2 = 0.991, and the linear regression equation was y=1.103 x - 0.0022 compared with the nephelometric method. By analyzing the receiver operating characteristic (ROC) curve of CRP combined with NLR to predict AL after Dixon surgery, the cut-off point was 0.11 on the first day after the surgery, the area under the curve was 0.896, the sensitivity was 82.5%, and the specificity was 76.67%. The cut-off point on the third day after the surgery was 0.13, the area under the curve was 0.931, the sensitivity was 86.67%, and the specificity was 90%. On the fifth day after the surgery, the cut-off point, the area under the curve, the sensitivity, and the specificity were 0.16, 0.964, 92.5%, and 95.83% in turn. In conclusion, PAA-Au/Fe3O4 magnetic nanoparticles could be used for clinical examination of patients with rectal cancer, and CRP combined with NLR could improve the prediction accuracy of AL after rectal cancer surgery.

Fully Saturated Hydrocarbons as Hosts of Optical Cycling Centers.

Designing closed, laser-induced optical cycling transitions in trapped atoms or molecules is useful for quantum information processing, precision measurement, and quantum sensing. Larger molecules that feature such closed transitions are particularly desirable, as the increased degrees of freedom present new structures for optical control and enhanced measurements. The search for molecules with robust optical cycling centers is a challenge which requires design principles beyond trial-and-error. Two such principles are proposed for the particular M-O-R framework, where M is an alkaline earth metal radical, and R is a ligand: (1) Large, saturated hydrocarbons can serve as ligands, R, due to a substantial HOMO-LUMO gap that encloses the cycling transition, so long as the R group is rigid. (2) Electron-withdrawing groups, via induction, can enhance Franck-Condon factors (FCFs) of the optical cycling transition, as long as they do not disturb the locally linear structure in the M-O-R motif. With these tools in mind, larger molecules can be trapped and used as optical cycling centers, sometimes with higher FCFs than smaller molecules.

Role of ORAI calcium release-activated calcium modulator 1 (ORAI1) on neutrophil extracellular trap formation in dairy cows with subclinical hypocalcemia.

Hypocalcemia in dairy cows is associated with decreased neutrophil phagocytosis, adhesion capacity, migration, and reactive oxygen species (ROS) production through alterations in ORAI calcium release-activated calcium modulator 1 (ORAI1). Neutrophils can resist the invasion of pathogenic microorganisms by releasing neutrophil extracellular traps (NET). However, the mechanisms controlling NET formation during hypocalcemia are unknown. To address the role of ORAI1 in NET formation, neutrophils were isolated at 2 d postcalving from lactating Holstein dairy cows (n = 10 per group) diagnosed as clinically healthy (control) or with plasma concentrations of Ca2+ <2.0 mmol/L as a criterion for diagnosing subclinical hypocalcemia (SCH). A series of ex vivo experiments were conducted as follows: first, neutrophils isolated from both groups of cows were treated with phorbol 12-myristate 13-acetate (PMA) to stimulate NET formation; second, neutrophils from control and SCH were pretreated with or without the ROS scavenger N-acetylcysteine (NAC), the sarcoendoplasmic Ca2+ ATPase inhibitor thapsigargin, or ORAI1 blocker 2APB and then treated with PMA to stimulate NET formation; and third, neutrophils were transfected with small interfering (si)ORAI1 or nontarget siRNA (siNEG) and then stimulated with PMA to induce formation of NET. A one-way ANOVA was used for statistical analysis of individual experiments. In the first experiment, neutrophils from SCH cows formed NET with fewer DNA filaments, more diffused nuclei, and reduced translocation of myeloperoxidase (MPO) and neutrophil elastase (NE) to the nucleus. Neutrophils from SCH cows stimulated with PMA had a lower mitochondrial permeability, the state of mitochondrial permeability transition pore was open, ROS production was lower and there was increased mitochondrial damage. In the second experiment, in both control and SCH-PMA stimulated neutrophils, exogenous NAC decreased NET formation (assessed via Hoechst 33342 dye; Beyotime). Furthermore, following the challenge with PMA, thapsigargin increased NET formation and ROS production, but blocking ORAI1 with 2APB decreased NADPH oxidase activation, ROS production, and NET formation. In the third experiment, neutrophils transfected with siORAI1 before stimulation with PMA had lower intracellular concentrations of Ca2+, NET formation, and ROS production. Overall, the data indicated that SCH reduces NET formation in neutrophils partly due to damaged mitochondria. The reduction in ORAI1 abundance in neutrophils of dairy cows with hypocalcemia also decreases ROS production.