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Abstract Background Diabetes-associated cognitive impairment (DACI) poses a significant challenge to the self-management of diabetes, markedly elevating the risk of adverse complications. A burgeoning body of evidence implicates microglia as a central player in the pathogenesis of DACI. Methods We utilized proteomics to identify potential biomarkers in high glucose (HG)-treated microglia, followed by gene knockdown techniques for mechanistic validation in vitro and in vivo. Results Our proteomic analysis identified a significant upregulation of AKAP8L in HG-treated microglia, with concurrent dysregulation of autophagy and inflammation markers, making AKAP8L a novel biomarker of interest. Notably, the accumulation of AKAP8L was specific to HG-treated microglia, with no observed changes in co-cultured astrocytes or neurons, a pattern that was mirrored in streptozotocin (STZ)-induced diabetic mice. Further studies through co-immunoprecipitation and proximity ligation assay indicated that the elevated AKAP8L in HG-treated microglial cells interacts with the mTORC1. In the STZ mouse model, we demonstrated that both AKAP8L knockdown and rapamycin treatment significantly enhanced cognitive function, as evidenced by improved performance in the Morris water maze, and reduced microglial activation. Moreover, these interventions effectively suppressed mTORC1 signaling, normalized autophagic flux, mitigated neuroinflammation, and decreased pyroptosis. Conclusions Our findings highlight the critical role of AKAP8L in the development of DACI. By interacting with mTORC1, AKAP8L appears to obstruct autophagic processes and initiate a cascade of neuroinflammatory responses. The identification of AKAP8L as a key mediator in DACI opens up new avenues for potential therapeutic interventions.

Abstract The effective isolation of rare target cells, such as circulating tumor cells, from whole blood is still challenging due to the lack of a capturing surface with strong target-binding affinity and non-target-cell resistance. Here we present a solution leveraging the flexibility of bacterial virus (phage) nanofibers with their sidewalls displaying target circulating tumor cell-specific aptamers and their ends tethered to magnetic beads. Such flexible phages, with low stiffness and Young’s modulus, can twist and adapt to recognize the cell receptors, energetically enhancing target cell capturing and entropically discouraging non-target cells (white blood cells) adsorption. The magnetic beads with flexible phages can isolate and count target cells with significant increase in cell affinity and reduction in non-target cell absorption compared to magnetic beads having rigid phages. This differentiates breast cancer patients and healthy donors, with impressive area under the curve (0.991) at the optimal detection threshold (>4 target cells mL−1). Immunostaining of captured circulating tumor cells precisely determines breast cancer subtypes with a diagnostic accuracy of 91.07%. Our study reveals the power of viral mechanical attributes in designing surfaces with superior target binding and non-target anti-fouling.

Mango has frequently encountered severe climate and environmental challenges such as low temperatures, seriously affecting the sustainable development of the industry. In the study, physiological measurements showed that the activities of superoxide dismutase (SOD) and peroxidase (POD) were found to be higher in Jinhuang (JH) mango plants than those of Tainong (TN) mango plants under cold stress, indicating cold tolerant (JH) and non-cold tolerant (TN) mango varieties were firstly determined. Subsequently, transcriptomics showed 8,337 and 7,996 differentially expressed genes (DEGs) were respectively identified in JH and TN mango varieties treated at 4 °C for 36 h, while more DEGs (10,683 and 10,723) were screened when treated at 4 °C for 72 h. Quantitative real-time PCR (qRT-PCR) of the selected DEGs confirmed their transcriptional levels displayed agreement to the transcriptome data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed two primary cold resistant regulation pathways, photosynthesis-antenna proteins pathway and photosynthesis pathway, were both significant annotated in the two mango varieties, indicating share the common regulation mechanism response to cold stress. However, five specific cold resistant pathways, such as amino acid and carbohydrate metabolisms, were identified in JH mango variety with cold stress for longer duration, indicating the specific regulation pathways in the cold tolerant mango varieties. Furthermore, 43 ethylene-responsive transcription factors (ERFs) were significantly annotated in JH mango after cold-treated for 72 h comparing with the control group, and three of them ERF109-1, ERF017-1 and ERF017-2 were highly expressed, which may play important regulatory roles in plant cold resistance. These results provided insights into the primary and specific molecular mechanisms of different mango varieties resistance to chill.

Cadherin-17 (CDH17) is an oncofetal molecule associated with poor prognostic outcomes of hepatocellular carcinoma (HCC), for which the treatment options are very limited. The present study investigates the therapeutic potential of a monoclonal antibody (Lic5) that targets the CDH17 antigen in HCC. In vitro experiments showed Lic5 could markedly reduce CDH17 expression in a dose-dependent manner, suppress β-catenin signaling, and induce cleavages of apoptotic enzymes caspase-8 and -9 in HCC cells. Treatment of animals in subcutaneous HCC xenograft model similarly demonstrated significant tumor growth inhibition (TGI) using Lic5 antibody alone (5 mg/kg, i.p., t.i.w.; ca.60-65% TGI vs. vehicle at day 28), or in combination with conventional chemotherapy regimen (cisplatin 1 mg/kg; ca. 85-90% TGI). Strikingly, lung metastasis was markedly suppressed by Lic5 treatments. Immunohistochemical and western blot analyses of xenograft explants revealed inactivation of the Wnt pathway and suppression of Wnt signaling components in HCC tissues. Collectively, anti-CDH17 antibody promises as an effective biologic agent for treating malignant HCC.

SARS-CoV-2–induced excessive inflammation in brain leads to damage of blood–brain barrier, hypoxic-ischemic injury, and neuron degeneration. The production of inflammatory cytokines by brain microvascular endothelial cells and microglia is reported to be critically associated with the brain pathology of COVID-19 patients. However, the cellular mechanisms for SARS-CoV-2–inducing activation of brain cells and the subsequent neuroinflammation remain to be fully delineated. Our research, along with others’, has recently demonstrated that SARS-CoV-2–induced accumulation and activation of mast cells (MCs) in mouse lung could further induce inflammatory cytokines and consequent lung damages. Intracerebral MCs activation and their cross talk with other brain cells could induce neuroinflammation that play important roles in neurodegenerative diseases including virus-induced neuro-pathophysiology. In this study, we investigated the role of MC activation in SARS-CoV-2–induced neuroinflammation. We found that (1) SARS-CoV-2 infection triggered MC accumulation in the cerebrovascular region of mice; (2) spike/RBD (receptor-binding domain) protein–triggered MC activation induced inflammatory factors in human brain microvascular endothelial cells and microglia; (3) MC activation and degranulation destroyed the tight junction proteins in brain microvascular endothelial cells and induced the activation and proliferation of microglia. These findings reveal a cellular mechanism of SARS-CoV-2–induced neuroinflammation.

Introduction Traditional Chinese medicine (TCM) may have special advantages in facilitating smoking cessation, but consensus on effectiveness is lacking. We aim to comprehensively review, update, and refine current evidence on TCM effectiveness and safety. Methods Nine databases were searched from their inception up to 28 February 2023. Systematic reviews (SRs) and meta-analysis of TCM for smoking cessation were identified and retrieved. Additional databases and hand searches of RCTs from included SRs were performed for data pooling. Cochrane ROB tools and AMSTAR-2 were used to evaluate the methodological quality of RCTs and SRs, respectively. RCT data are presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) using RevMan 5.4. Results Thirteen SRs involving 265 studies with 33081 participants were included. Among these 265 studies, 157 were duplicates (58.36%) and 52 were non-RCTs (19.62%). Combined with the remaining 56 RCTs identified through hand searches, 88 RCTs involving 12434 participants were finally included for data synthesis. All the SRs focused on acupoint stimulation, and the majority were of low or very low quality. The methodological quality of RCTs was either unclear or high risk. For continuous abstinence rate, TCM external interventions were better than placebo in 6 months to 1 year (RR=1.60; 95% CI: 1.14–2.25; I2=27%; n=5533 participants). Compared with placebo, TCM external application was effective in reducing nicotine withdrawal symptoms, and the effect was gradually stable and obvious in the fourth week (MD= -4.46; 95% CI: -5.43 – -3.49; n=165 participants). Twelve RCTs reported adverse events as outcome indicators for safety evaluation, and no serious adverse events occurred. Conclusions Despite the methodological limitations of the original studies, our review suggests that TCM intervention shows potential effectiveness on the continuous abstinence rate. Extending the intervention time can enhance the effect of TCM on nicotine withdrawal symptoms. Referred to adverse events, more data for safety evaluation are required.

Introduction Quitting smoking, the critical path to reach the global targets of reducing tobacco use, can bring major and immediate health benefits to smokers. Exploring factors that help individuals to quit smoking is of great importance. The present study explored influencing factors on smoking cessation, in order to provide comprehensive reference for tobacco control policies. Methods Ex-smokers and current smokers were recruited online in this crosssectional survey, from 1 October to 31 November 2022, in China. The observational data were collected using a questionnaire to collect information with respect to sociodemographic characteristics of smokers, attitudes towards smoking cessation, details of smoking cessation, and different potential factors related to smoking cessation through open-ended questions. Results A total of 638 smokers from 30 provinces were recruited as eligible respondents, with a mean age of 37.3 ± 11.7 years and a mean smoking history of 15.9 ± 13.7 years. The percentage of males was 92.3%. Of the 638 respondents, only 3.9% had no intention to stop smoking. Among 155 subjects who had quitted smoking successfully, willpower (55.5%) was considered as the most important contributing factor. Among 365 subjects who tried to quit but failed, lack of willpower (28.2%), tobacco dependence (16.2%), influence of surrounding smokers or smoking environments (15.9%), bad moods (9.9%), stress from work or life (7.9%), habits (7.1%), socialization (4.1%), and easy availability of tobacco (2.7%) were considered as the adverse factors leading to failure in quitting smoking. Conclusions Willpower and support from family members were the vital factors that lead to successful smoking cessation. Future tobacco control policies should also focus on addressing withdrawal symptoms and creating smoke-free environments as well as other factors.

Identifying and selecting high-quality seeds is crucial for improving crop yield. The purpose of this study was to improve the selection of crop seeds based on separating vital seeds from dead seeds, by predicting the potential germination ability of each seed, and thus improving seed quality. The methods of oxygen consumption (Q) of seeds and the headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) were evaluated for identifying the viability of individual seeds. Firstly, the oxygen consumption technique showed clear differences among the values related to respiratory characteristics for seeds that were either vital or not, and the discrimination ability of final oxygen consumption (Q120) was achieved not only in sweet corn seeds but also in pepper and wheat seeds. Besides, Qt was established as a new variable to shorten the measuring process in the Q2 (oxygen sensor) procedure, which was significantly related to the viability of individual seeds. To minimize seed damage during measurement, the timing for viability evaluation was pinpointed at the 12, 6 and 9 h for pepper, sweet corn, and wheat seeds based on the new variables concerning oxygen consumption (i.e., Q12, Q6 and Q9, respectively). The accuracies of viability prediction were 91.9, 97.7 and 96.2%, respectively. Dead seeds were identified and hence discarded, leading to an enhancement in the quality of the seed lot as indicated by an increase in germination percentage, from 86.6, 90.9, and 53.8% to all at 100%. We then used the HS-GC-IMS to determine the viability of individual sweet corn seeds, noting that corn seed has a heavier weight so the volatile gas components are more likely to be detected. A total of 48 chromatographic peaks were identified, among which 38 target compounds were characterized, including alcohols, aldehydes, acids and esters. However, there were no significant differences between the vital and dead seeds, due to the trace amount volatile composition differences among the individual seeds. Furthermore, a PCA based on the signal intensities of the target volatile compounds obtained was found to lose its effectiveness, as it was unable to distinguish those two types of sweet corn seeds. These strategies can provide a reference for the rapid detection of single seed viability.

HIV-1 latency posts a major obstacle for HIV-1 eradication. Currently, no desirable latency reversing agents (LRAs) have been implicated in the “Shock and Kill” strategy to mobilize the latently infected cells to be susceptible for clearance by immune responses. Identification of key cellular pathways that modulate HIV-1 latency helps to develop efficient LRAs. In this study, we demonstrate that the Wnt downstream β-catenin/TCF1 pathway is a crucial modulator for HIV-1 latency. The pharmacological activation of the β-catenin/TCF1 pathway with glycogen synthase kinase-3 (GSK3) inhibitors promoted transcription of HIV-1 proviral DNA and reactivated latency in CD4+ T cells; the GSK3 kinase inhibitor 6-bromoindirubin-3′-oxime (6-BIO)-induced HIV-1 reactivation was subsequently confirmed in resting CD4+ T cells from cART-suppressed patients and SIV-infected rhesus macaques. These findings advance our understanding of the mechanisms responsible for viral latency, and provide the potent LRA that can be further used in conjunction of immunotherapies to eradicate viral reservoirs.

Human pegivirus (HPgV-1), previously known as GB virus C (GBV-C) or hepatitis G virus (HGV), is a single-stranded positive RNA virus belonging to the genus Pegivirus of the Flaviviridae family. It is transmitted by percutaneous injuries (PIs), contaminated blood and/or blood products, sexual contact, and vertical mother-to-child transmission. It is widely prevalent in general population, especially in high-risk groups. HPgV-1 viremia is typically cleared within the first 1–2 years of infection in most healthy individuals, but may persist for longer periods of time in immunocompromised individuals and/or those co-infected by other viruses. A large body of evidences indicate that HPgV-1 persistent infection has a beneficial clinical effect on many infectious diseases, such as acquired immunodeficiency syndrome (AIDS) and hepatitis C. The beneficial effects seem to be related to a significant reduction of immune activation, and/or the inhabitation of co-infected viruses (e.g. HIV-1). HPgV-1 has a broad cellular tropism for lymphoid and myeloid cells, and preferentially replicates in bone marrow and spleen without cytopathic effect, implying a therapeutic potential. The paper aims to summarize the natural history, prevalence and distribution characteristics, and pathogenesis of HPgV-1, and discuss its association with other human viral diseases, and potential use in therapy as a biovaccine or viral vector.

Summary: Single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) allows the dissection of transcriptional changes in immune cells with HIV infection. Here, we isolate PBMCs from HIV-infected individuals. After counting the cell number and verifying cell viability, we perform scRNA-seq for PBMCs on the 10× Genomics protocol and the Illumina NovaSeq 6000 sequencing platform. Furthermore, we analyze the function and cellular trajectories of B cell subsets and B cell receptor (BCR) repertoire after filtering raw sequences data and normalizing gene expression.For complete details on the use and execution of this protocol, please refer to Jia et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract The slip and instability mechanisms of coal-rock parting-coal structures under uniaxial loading conditions were investigated using experiments and case verification. The slip and the corresponding precursors were described by monitoring the displacement, strain, and acoustic emissions (AEs) of coal and rock parting blocks during testing, and the experimental results were verified by analyzing the microseismic (MS) effects during the working face advancing in a coal seam bifurcation area. The main conclusions were as follows: (1) each slip of the discontinuities sandwiched between coal and rock parting produced shear and tensile cracks, but the shear cracks was dominant; (2) for the instability mode that was characterized by low peak stress, high energy release, and a stable b value of AE, each slip corresponds to a peak frequency of AE, which can reveal the final instability mode; (3) the sudden drop in the fault total area of AE can be regarded as a precursor for the warning fracture or slip instability of a discontinuity; and (4) the MS events in the coal seam bifurcation area were mainly characterized by a wide frequency and high amplitude, especially near the coal bifurcation line, where there were obvious characteristics of low-frequency shear fracture for the MS events. This study is relevant for the early warning of coal-rock dynamic disasters triggered by the slip, fracture, and instability of coal-rock parting compound structures in coal mines.

Objectives To conduct a comprehensive analysis in Hainan centenarians on the link between sleep status and their blood pressure status. Furthermore, the study also aims to explore how inflammatory indicators may mediate the relationship. Methods The China Hainan Centenarians Cohort Study (CHCCS) collected baseline data on sleep status, inflammatory indicators, and blood pressure data. The study used a mediation model to investigate how inflammatory indicators mediate the relationship between sleep status and blood pressure status. Result In this study, a total of 967 centenarians were included. The prevalence of hypertension among the centenarians was 71.4%. The analysis showed that centenarians with poor sleep quality had a 43% higher risk of hypertension compared to those with normal sleep quality (OR = 1.43, 95% CI: 1.03-1.97). Additionally, centenarians with nighttime sleep durations of = 6 h or > 9 h had higher proportions of high pulse pressure (PP), with OR values of 1.76 (95% CI: 1.18-2.63) and 2.07 (95% CI: 1.34-3.19), respectively. Mediation analysis illustrated that complement C3 played a mediating role in the relationship between sleep quality and hypertension, with an effect ratio of 2.4%. Similarly, lymphocyte count, the neutrophil-to-lymphocyte ratio (NLR), and the systemic immune-inflammation index (SII) were identified as mediating factors in the association between nighttime sleep duration and high PP, with effect ratios of 91.22%, 36.93%, and 0.20%, respectively. Conclusion In centenarians, poor sleep quality raises the risk of hypertension, with complement C3 as a mediator. Additionally, nighttime sleep durations of = 6 h or > 9 h increases the risk of high PP, mediated by lymphocyte count, NLR, and SII. [ABSTRACT FROM AUTHOR]

In the past few years, ionic liquids (ILs)-based gels (gels contain ILs) have become a research hotspot. ILs-based gels combine the properties of gels with intrinsic ILs properties. According to the existence form and function of the ILs in the gel, the ILs-based gels are divided into three types. One is ILs hydrogels which the PILs, ILs polymerized into poly-ionic liquids, copolymerized with other polymers served as the continuous phase in the gel system. This type of gel can usually absorb water and is an ILs hydrogel. The other is ionic gels that are usually synthesized by high-molecular organic polymers as spatial network structure and ILs as a dispersed phase, which maintained the good performance of ILs. The third one is that the ILs acts as both the continuous phase and the dispersed phase of the gels. In all research fields, the pursuit of new materials aims at functional materials, which enhances specific and efficiency, and ultimately applications. The application of ILs-based gels ranges from energy storage, sensing, electrochemical devices, to antibacterial and gas capture. Different synthesis methods have different performances and applications of ILs-based gels. The purpose of this review is to provide the latest developments on ILs-based gels, perspectives on several applications, and some challenges that need to be aware of in this field.

A schematic illustration of SARS-CoV-2 triggers MC rapid degranulation to induce alveolar epithelial inflammation and lung injury. SARS-CoV-2 triggers an immediate mast cell (MC) degranulation, which initiates the alveolar epithelial inflammation and disrupts the tight junction. MC stabilizers that block degranulation reduce virus-induced lung inflammation and injury.

Summary: Incomplete immune reconstitution happens in some HIV-infected patients who have achieved persistent viral suppression under antiretroviral therapy (ART). We performed single-cell RNA sequencing for peripheral blood mononuclear cells to analyze B cell receptor (BCR) repertoire and B cell subtypes in health controls (non-HIV-infected, HCs), HIV-infected immunological responders (IRs), and immunological nonresponders (INRs). We found that the dominant usage of IGHV gene segments of naïve B cells and memory B cells were IGHV3 and IGHV4, and the diversity of BCR repertoire was decreased in INRs. Differentiation trajectory analysis showed that the low differentiation of naïve B cells was related to satisfactory immune status. The cell cycle of B cells with immune-specific genes of IgD+ B cells was degraded in INRs, which was mediated by the anaphase-promoting complex/cyclosome pathway in the phase of G2/M checkpoints. These findings provide significant insights to understand the function of B cell-mediated immune response in immune reconstitution after HIV infection.

ABSTRACT HIV-1 CRF07_BC originated among injection drug users (IDUs) in China. After diffusing into men who have sex with men (MSM), CRF07_BC has shown a rapid expansion in this group; however, the mechanism remains unclear. Here, we identified a new K28E32 variant of CRF07_BC that was characterized by five specific mutations (E28K, K32E, E248V, K249Q, and T338S) in reverse transcriptase. This variant was mainly prevalent among MSM, and was overrepresented in transmission clusters, suggesting that it could have driven the rapid expansion of CRF07_BC in MSM, though founder effects cannot be ruled out. It was descended from an evolutionary intermediate accumulating four specific mutations and formed an independent phylogenetic node with an estimated origin time in 2003. The K28E32 variant was demonstrated to have significantly higher in vitro HIV-1 replication ability than the wild type. Mutations E28K and K32E play a critical role in the improvement of in vitro HIV-1 replication ability, reflected by improved reverse transcription activity. The results could allow public health officials to use this marker (especially E28K and K32E mutations in the reverse transcriptase (RT) coding region) to target prevention measures prioritizing MSM population and persons infected with this variant for test and treat initiatives. IMPORTANCE HIV-1 has very high mutation rate that is correlated with the survival and adaption of the virus. The variants with higher transmissibility may be more selective advantage than the strains with higher virulence. Several HIV-1 variants were previously demonstrated to be correlated with higher viral load and lower CD4 T cell count. Here, we first identified a new variant (the K28E32 variant) of HIV-1 CRF07_BC, described its origin and evolutionary dynamics, and demonstrated its higher in vitro HIV-1 replication ability than the wild type. We demonstrated that five RT mutations (especially E28K and K32E) significantly improve in vitro HIV-1 replication ability. The appearance of the new K28E32 variant was associated with the rapidly increasing prevalence of CRF07_BC among MSM.

The incidence of infections caused by the H7N9 subtype of the influenza virus has expanded rapidly in China in recent decades, generating massive economic loss and posing a significant threat to public health. In the absence of specialized antiviral treatments or long-term effective preventative vaccinations, it is critical to constantly enhance vaccines and create effective antiviral drugs to prevent the recurrence of pandemics. In the present study, a transmembrane-substituted (TM) virus-like particle (VLP)-based vaccine was created by replacing the transmembrane region of hemagglutinin (HA) protein with the transmembrane region of the H3 HA protein and then used to immunize BALB/c mice. Sera and T cells were collected from the immunized mice to evaluate the passive immune effects. Our results showed that naïve mice achieved 80–100% protection against homologous and heterologous H7N9 influenza strains after receiving passive serum immunization; the protective effect of the TM VLPs was more evident than that of the wild-type HA VLPs. In contrast, mice immunized with passive T cells achieved only 20 to 80% protection against homologous or heterologous strains. Our findings significantly contribute to understanding the control of the H7N9 virus and the development of a vaccine.

Objective To evaluate the usefulness of a 3D‐printed model for transoral atlantoaxial reduction plate (TARP) surgery in the treatment of irreducible atlantoaxial dislocation (IAAD). Methods A retrospective review was conducted of 23 patients (13 men, 10 women; mean age 58.17 ± 5.27 years) with IAAD who underwent TARP from January 2015 to July 2017. Patients were divided into a 3D group (12 patients) and a non‐3D group (11 patients). A preoperative simulation process was undertaken for the patients in the 3D group, with preselection of the TARP system using a 3D‐printed 1:1 scale model, while only imaging data was used for the non‐3D group. Complications, clinical outcomes (Japanese Orthopaedic Association [JOA] and visual analogue score [VAS]), and image measurements (atlas–dens interval [ADI], cervicomedullary angle [CMA], and clivus‐canal angle [CCA]) were noted preoperatively and at the last follow up. Results A total of 23 patients with a follow‐up time of 16.26 ± 4.27 months were included in the present study. The surgery duration, intraoperative blood loss, and fluoroscopy times in the 3D group were found to be shorter than those in non‐3D group, with statistical significance. The surgery duration was 3.29 ± 0.45 h in the 3D group and 4.68 ± 0.90 h in the non‐3D group, and the estimated intraoperative blood loss was 131.67 ± 43.03 mL in the 3D group and 185.45 ± 42.28 mL in the non‐3D group. No patients received blood transfusions. The intraoperative fluoroscopy times were 5.67 ± 0.89 in the 3D group and 7.91 ± 1.45 in the non‐3D group. Preoperatively and at last follow up, JOA and VAS scores and ADI, CCA, and CMA were improved significantly within the two groups. However, no statistical difference was observed between the two groups. However, surgical site infection occurred in 1 patient in the 3D group, who underwent an emergency revision operation of the removal of TARP device and posterior occipitocervical fixation; the patient recovered 2 weeks after the surgery. In 2 patients in the traditional group, a mistake occurred in the placement of screws, with no neurological symptoms related to the misplacement. Conclusion Preoperative surgical simulation using a 3D‐printed real‐size model is an intuitive and effective aid for TARP surgery for treating IAAD. The 3D‐printed biomodel precisely replicated patient‐specific anatomy for use in complicated craniovertebral junction surgery. The information was more useful than that available with 3D reconstructed images.

Abstract Background The Styracaceae are a woody, dicotyledonous family containing 12 genera and an estimated 160 species. Recent studies have shown that Styrax and Sinojackia are monophyletic, Alniphyllum and Bruinsmia cluster into a clade with an approximately 20-kb inversion in the Large Single-Copy (LSC) region. Halesia and Pterostyrax are not supported as monophyletic, while Melliodendron and Changiostyrax always form sister clades. Perkinsiodendron and Changiostyrax are newly established genera of Styracaceae. However, the phylogenetic relationship of Styracaceae at the generic level needs further research. Results We collected 28 complete plastomes of Styracaceae, including 12 sequences newly reported here and 16 publicly available sequences, comprising 11 of the 12 genera of Styracaceae. All species possessed the typical quadripartite structure of angiosperm plastomes, with sequence differences being minor, except for a large 20-kb (14 genes) inversion found in Alniphyllum and Bruinsmia. Seven coding sequences (rps4, rpl23, accD, rpoC1, psaA, rpoA and ndhH) were identified to possess positively selected sites. Phylogenetic reconstructions based on seven data sets (i.e., LSC, SSC, IR, Coding, Non-coding, combination of LSC + SSC and concatenation of LSC + SSC + one IR) produced similar topologies. In our analyses, all genera were strongly supported as monophyletic. Styrax was sister to the remaining genera. Alniphyllum and Bruinsmia form a clade. Halesia diptera does not cluster with Perkinsiodendron, while Perkinsiodendron and Rehderodendron form a clade. Changiostyrax is sister to a clade of Pterostyrax and Sinojackia. Conclusion Overall, our results demonstrate the power of plastid phylogenomics in improving estimates of phylogenetic relationships among genera. This study also provides insight into plastome evolution across Styracaceae.

The low-wavenumber components in the gradient of full waveform inversion (FWI) play a vital role in the stability of the inversion. However, when FWI is implemented in some high frequencies and current models are not far away from the real velocity model, an excessive number of low-wavenumber components in the gradient will also reduce the convergence rate and inversion accuracy. To solve this problem, this paper firstly derives a formula of scattering angle weighted gradient in FWI, then proposes a hybrid gradient. The hybrid gradient combines the conventional gradient of FWI with the scattering angle weighted gradient in each inversion frequency band based on an empirical formula derived herein. Using weighted hybrid mode, we can retain some low-wavenumber components in the initial lowfrequency inversion to ensure the stability of the inversion, and use more high-wavenumber components in the high-frequency inversion to improve the convergence rate. The results of synthetic data experiment demonstrate that compared to the conventional FWI, the FWI based on the proposed hybrid gradient can effectively reduce the low-wavenumber components in the gradient under the premise of ensuring inversion stability. It also greatly enhances the convergence rate and inversion accuracy, especially in the deep part of the model. And the field marine seismic data experiment also illustrates that the FWI based on hybrid gradient (HGFWI) has good stability and adaptability. [ABSTRACT FROM AUTHOR]

Abstract. Background:. Recent evidence has shown that prophylactic antibiotic treatment in patients with acute pancreatitis is not associated with a significant decrease in mortality or morbidity. The use and efficacy of prophylactic antibiotic treatment in acute pancreatitis remain controversial. This meta-analysis was conducted to assess whether antibiotic prophylaxis is beneficial in patients with acute pancreatitis. Methods:. We searched randomized controlled trials (RCTs) of prophylactic use of antibiotics using Medline (PubMed), Embase, the Cochrane Library, and Web of Science. The data were analyzed using Review Manager 5.3 software. We performed pooled analyses for infected pancreatic necrosis, mortality, surgical intervention, and non-pancreatic infection. Odds ratios (ORs) from each trial were pooled using a random or fixed effects model, depending on the heterogeneity of the included studies. Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity, when necessary. Results:. Totally, 11 RCTs involving 747 participants were included, with an intervention group (prophylactic use of antibiotics, n = 376) and control group (n = 371). No significant differences were found regarding antibiotic prophylaxis with respect to incidence of infected pancreatic necrosis (OR, 0.74; 95% confidence interval [CI], 0.50–1.09; P = 0.13), surgical intervention (OR, 0.92; 95% CI, 0.62–1.38; P = 0.70), and morality (OR, 0.71; 95% CI, 0.44–1.15; P = 0.16). However, antibiotic prophylaxis was associated with a statistically significant reduction in the incidence of non-pancreatic infection (OR, 0.59; 95% CI, 0.42–0.84; P = 0.004). Conclusions:. Prophylactic antibiotics can reduce the incidence of non-pancreatic infection in patients with AP.

Mast cells (MCs) are strategically located at the host-environment interface and their non-allergic roles in the immune-surveillance of pathogens have recently gained more attention. However, MC-caused detrimental regulation of immune inflammations can promote viral invasion. Currently, the role of MCs in retroviral infection remains elusive. We have recently proved that human gut MCs could capture and transfer HIV-1 to CD4+ T cells for promoting viral spread; MC-released histamine augments HIV-1-induced functional polarization of dendritic cells to cause immunosuppression via stimulating the differentiation of regulatory T cells. In this study, we used a murine model of MuLV/Friend virus infection to address MC role in acute retroviral infection in vivo. The acute infection of MuLV/Friend virus could be established in C57BL/6 wild type mice, but viral acquisition showed low efficiency in C57BL/6-KitW–sh/W–sh (Sash) mice which lack MCs. In mechanism, we found that MuLV/Friend virus triggered MC activation for degranulation; MC degranulation subsequently activated the granulocyte-like myeloid derived suppressive cells (G-MDSCs) to inhibit CD8+ T cells- and NK cells-mediated antiviral immune responses. The reconstruction of MCs in Sash mice promoted acute retroviral infection by regulating G-MDSCs functions and antiviral immune responses. Importantly, the administration of MC stabilizers to block cell degranulation elevated antiviral immune response and consequently suppressed retrovirus infection. This study uncovers a specific role of MCs in acute retroviral infection and elucidates the underlying immune-mechanisms. Targeting MCs may provide a novel approach for controlling acute infection by retroviruses.

In order to maximize the total spectrum efficiency and improve the Quality of Experience (QoE) on Elastic Optical Network (EON), an adaptive modulation method based on Deep Neural Network (DNN) is proposed. Firstly, the network transmission quality in optical fiber is estimated. Then, the route length, hop number and video quality are taken as the three parameters of the request characteristics, and the deep learning method is adopted to selected the modulation system with the maximum spectrum efficiency according to the desired QoE of each requirement. The simulation results show that the average spectral efficiency of the proposed method is 51%and 32%higher in National Science Foundation (NSF) network than that of distance adaptive method and integer programming method, and 43%and 29%higher in China Network (CN) backbone network. In addition, the blocking probability of the proposed method is 0.01 lower than that of the distance adaptive method and integer programming method.

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation. [ABSTRACT FROM AUTHOR]

Cross-linking mass spectrometry can provide insights into protein structures and interactions but its scope depends on the reactivity of the cross-linker. Here, the authors develop Arg-Arg and Lys-Arg cross-linkers, which provide structural information elusive to the widely used Lys-Lys cross-linkers.

Mechanical threshing used when preparing maize seeds for planting subjects seed to damage and reduces seed quality. The purpose of this study was to assess the effect of mechanical threshing on the quality of maize seed threshed at different moisture contents (MCs). Seeds of dent maize JK968 and flint maize DD2 were threshed at 12, 15, 18, 21, and 24% MC. The damage degree was determined by iodine staining, and seed vigor was assessed by standard germination (SG), cold test germination (CTG), accelerated aging germination (AAG), seedling emergence rate, and seedling root and shoot length. The results showed that the damage percentage increased, and the seed vigor parameters decreased with increasing seed MC during threshing in both cultivars. For obtaining high seed quality, indicated by at least 90, 85, and 80% of SG, AAG, and CTG, respectively, JK 968 and DD2 should be threshed at MC lower than 15 and 18%, respectively. Furthermore, the damage mainly occurred in the apical part of seeds, irrespective of the threshing MC in both cultivars. When the embryo was damaged, seedling emergence rates were significantly reduced with great influence on shoot length. Damage to the endosperm resulted in little effect on seedling performance. Flint maize DD2 was more tolerant to mechanical threshing than dent maize JK968. These results provided technical reference for the production and processing of high vigor maize seeds.

Abstract Objective To discuss the diagnostic value of multislice spiral tomography (CT) combined with CT angiography (CTA) technology in intra-abdominal undescended testis secondary seminoma cases. Methods We retrospectively analyzed the CT and CTA imaging features of CT and CTA findings of nine patients with an intra-abdominal undescended testis secondary seminoma. Results The tumors in all nine patients were mainly solid, and the average CT value was 38.4 ± 3.4 HU. Low-density areas of various sizes were visible in the tumors, and calcifications were detected in two patients. The tumors in eight patients had a complete capsule, which pressed on the surrounding structures. In one patient, the tumor had an incomplete capsule, which invaded the surrounding structures. Some of the solid tumors showed progressive and slight enhancement on the CT-enhanced scans. The values in the arterial phase, venous phase, and delayed phase were 46.3 ± 5.1 (40–55 HU), 57.3 ± 7.3HU (48–68 HU), and 65.1 ± 7.2HU (56–77 HU), respectively, with an average increase rate of 27.0 ± 7.2 HU. No enhancement was found in low-density areas on the CTA scans, and the supply arteries of the tumors in the nine patients all originated from the abdominal aortic wall 2–3 cm below the renal ostia. These arteries became thickened and tortuous when near the tumors, and there were no branching vessels. In eight patients, the supply arteries of the tumors originated from the posterior tumor and ended inside the tumor, and they originated from anterior of the tumor in one patient. Testicular venous drainage was detected in three patients, and lymph node metastasis in the abdominal aorta detected in two cases. Conclusion An intra-abdominal undescended testis secondary seminoma exhibits a characteristic appearance on CT. CTA shows a three-dimensional testicular vascular pedicle sign of a seminoma. A combination of CT and CTA can improve the diagnostic accuracy of an intra-abdominal undescended testis secondary seminoma.

Here, the authors determine the respiratory virome and serum cytokine profile in children diagnosed with acute respiratory tract infections (ARTI) and show that relative abundance of Propionibacterium phages as well as serum levels of TIMP-1 and PDGF-BB are increased in multiple ARTIs compared with single ARTI.

Molecular-glue degraders mediate interactions between target proteins and components of the ubiquitin-proteasome system to cause selective protein degradation. Here, we report a new molecular glue HQ461 discovered by high-throughput screening. Using loss-of-function and gain-of-function genetic screening in human cancer cells followed by biochemical reconstitution, we show that HQ461 acts by promoting an interaction between CDK12 and DDB1-CUL4-RBX1 E3 ubiquitin ligase, leading to polyubiquitination and degradation of CDK12-interacting protein Cyclin K (CCNK). Degradation of CCNK mediated by HQ461 compromised CDK12 function, leading to reduced phosphorylation of a CDK12 substrate, downregulation of DNA damage response genes, and cell death. Structure-activity relationship analysis of HQ461 revealed the importance of a 5-methylthiazol-2-amine pharmacophore and resulted in an HQ461 derivate with improved potency. Our studies reveal a new molecular glue that recruits its target protein directly to DDB1 to bypass the requirement of a substrate-specific receptor, presenting a new strategy for targeted protein degradation.

ABSTRACT Reversible repression of HIV-1 5′ long terminal repeat (5′-LTR)-mediated transcription represents the main mechanism for HIV-1 to maintain latency. Identification of host factors that modulate LTR activity and viral latency may help develop new antiretroviral therapies. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are known to regulate gene expression and possess multiple physiological functions. hnRNP family members have recently been identified as the sensors for viral nucleic acids to induce antiviral responses, highlighting the crucial roles of hnRNPs in regulating viral infection. A member of the hnRNP family, X-linked RNA-binding motif protein (RBMX), has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5′-LTR-driven transcription of viral genome in CD4+ T cells. Mechanistically, RBMX binds to HIV-1 proviral DNA at the LTR downstream region and maintains the repressive trimethylation of histone H3 lysine 9 (H3K9me3), leading to a blockage of the recruitment of the positive transcription factor phosphorylated RNA polymerase II (RNA pol II) and consequential impediment of transcription elongation. This RBMX-mediated modulation of HIV-1 transcription maintains viral latency by inhibiting viral reactivation from an integrated proviral DNA. Our findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies. IMPORTANCE HIV-1 latency featuring silence of transcription from HIV-1 proviral DNA represents a major obstacle for HIV-1 eradication. Reversible repression of HIV-1 5′-LTR-mediated transcription represents the main mechanism for HIV-1 to maintain latency. The 5′-LTR-driven HIV gene transcription can be modulated by multiple host factors and mechanisms. The hnRNPs are known to regulate gene expression. A member of the hnRNP family, RBMX, has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5′-LTR-driven transcription of viral genome in CD4+ T cells and maintains viral latency. These findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.

This research aimed to improve selection of pepper seeds for separating high-quality seeds from low-quality seeds. Past research has shown that seed vigor is significantly related to the seed color and size, thus several physical features were identified as candidate predictors of high seed quality. Image recognition software was used to automate recognition of seed feature quality using 400 kernels of pepper cultivar 101. In addition, binary logistic regression and a neural network were applied to determine models with high predictive value of seed germination. Single-kernel germination tests were conducted to validate the predictive value of the identified features. The best predictors of seed vigor were determined by the highest correlation observed between the physical features and the subsequent fresh weight of seedlings that germinated from the 400 seeds. Correlation analysis showed that fresh weight was significantly positively correlated with eight physical features: three color features (R, a*, brightness), width, length, projected area, and single-kernel density, and weight. In contrast, fresh weight significantly negatively correlated with the feature of hue. In analyses of two of the highest correlating single features, germination percentage increased from 59.3 to 71.8% when a*≥3, and selection rate peaked at 57.8%. Germination percentage increased from 59.3 to 79.4%, and the selection rate reached 76.8%, when single-kernel weight ≥0.0064 g. The most effective model was based on a multilayer perceptron (MLP) neural network, consisting of 15 physical traits as variables, and a stability calculated as 99.4%. Germination percentage in a calibration set of seeds was 79.1% and the selection rate was 90.0%. These results indicated that the model was effective in predicting seed germination based on physical features and could be used as a guide for quality control in seed selection. Automated systems based on machine vision and model classifiers can contribute to reducing the costs and labor required in the selection of pepper seeds.

ABSTRACT Multiple cellular metabolic pathways are altered by HIV-1 infection, with an impact on immune activation, inflammation, and acquisition of non-AIDS comorbid diseases. The dysfunction of tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the underlying mechanism remains unknown. In this study, we demonstrated that the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, is activated by Trp metabolites to promote HIV-1 infection and reactivation. AHR directly binds to the HIV-1 5′ long terminal repeat (5′-LTR) at the molecular level to activate viral transcription and infection, and AHR activation by Trp metabolites increases its nuclear translocation and association with the HIV 5′-LTR; moreover, the binding of AHR with HIV-1 Tat facilitates the recruitment of positive transcription factors to viral promoters. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection. IMPORTANCE Cellular metabolic pathways that are altered by HIV-1 infection may accelerate disease progression. Dysfunction in tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the mechanism responsible was not known. This study demonstrates that Trp metabolites augment the activation of aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, to promote HIV-1 infection and transcription. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection.