Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury.

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.

Secondary metabolites in host pears defense against two fruit borers and cytochrome-P450-mediated counter-defense.

Herbivorous insects have evolved metabolic strategies to survive the challenges posed by plant secondary metabolites (SMs). This study reports an exploration of SMs present in pears, which serve as a defense against invasive Cydia pomonella and native Grapholita molesta and their counter-defense response. The feeding preferences of fruit borers are influenced by the softening of two pear varieties as they ripen. The content of SMs, such as quercetin and rutin, increases due to feeding by fruit borers. Notably, quercetin levels only increase after C. pomonella feeding. The consumption of SMs affects the growth of fruit borer population differently, potentially due to the activation of P450 genes by SMs. These two fruit borers are equipped with specific P450 enzymes that specialize in metabolizing quercetin and rutin, enabling them to adapt to these SMs in their host fruits. These findings provide valuable insights into the coevolution of plants and herbivorous insects.

CRISPR/Cas9-mediated ebony knockout causes melanin pigmentation and prevents moth Eclosion in Ectropis grisescens.

Ectropis grisescens (Lepidoptera: Geometridae) is a destructive tea pest in China. Mimesis, characterized by changing body color, is an important trait of E. grisescens larvae. Hence, identifying melanin pathway-related genes may contribute to developing new pest control strategies. In the present study, we cloned Egebony, a gene potentially involved in melanin pigmentation in E. grisescens, and subsequently conducted CRISPR/Cas9-mediated targeted mutagenesis of Egebony to analyze its role in pigmentation and development. At the larvae, prepupae, and pupae stages, Egebony-knockout individuals exhibited darker pigmentation than the wild-type. However, Egebony knockout did not impact the colors of sclerotized appendants, including ocelli, setae, and claws. While mutant pupae could successfully develop into moths, they were unable to emerge from the puparium. Notably, embryo hatchability and larval survival of mutants remained normal. Further investigation indicated that mutant pupae exhibited significantly stronger shearing force than the wild-type, with the pigmented layer of mutant pupae appearing darker and thicker. Collectively, these results suggest that the loss of Egebony might increase the rigidity of the puparium and prevent moth eclosion. This study provides new insights into understanding the function and diversification of ebony in insect development and identifies a lethal gene that can be manipulated for developing effective pest control strategies.

Training in a wearable exoskeleton improves the lower limb motor recovery of stroke survivors / 中华物理医学与康复杂志

Objective:To explore any differential effect of training wearing a unilateral exoskeleton on the lower-limb motor function of stroke survivors.Methods:Forty stroke survivors were randomly divided into an exoskeleton group ( n=20) and a control group ( n=20). The control group performed conventional lower extremity exercise training while the exoskeleton group received exoskeleton-assisted lower-limb physical therapy. Each participant received eighteen 40-minute training sessions over three weeks. Before and after the intervention, the walking ability, lower-limb function, balance and ability in the activities of daily living of both groups were evaluated. Integrated electromyography (iEMG) of the rectus femoris and tibialis anterior of both legs was also recorded during sit-to-stand transitions to assess the activation of the affected muscles and the symmetry of bilateral muscle activation. Results:After the three weeks, significant improvement was observed in all of the measurements in both groups, but with the exoskeleton group scoring significantly better on average in functional ambulation category grading (1.63±0.72). Both groups′ iEMGs had also improved significantly compared with before treatment, but the exoskeleton group′s average result was by that time significantly better than the control group′s average.Conclusions:A wearable exoskeleton can effectively improve the rehabilitation of walking, lower limb movement, balance and skill in the activities of daily living of persons with subacute stroke. It better activates the affected lower limb muscles and improves the symmetry of bilateral lower limb muscle activation.

The effects of activating the reticulospinal tract on anticipatory postural adjustments in fine motor movements of the upper extremities / 中华物理医学与康复杂志

Objective:To observe any dependence of anticipatory postural adjustment (APA) on the difficulty of fine upper limb tasks and to document any effect of reticulospinal tract (RST) facilitation on APAs during such tasks.Methods:The study′s bivariate mixed design involved 4 different tasks and 3 different priming states. Thirteen healthy, male, right-handed subjects were recruited. They were asked to complete the 4 tasks of reaching, grasping a cup, pinching a card using the thumb or using the little finger, respectively for 10 times 1 in response to two different starting cues delivered through an earphone. Half of the trials with each task were initiated with 114dB white noise to startle and activate the reticulospinal tract (RST), while the others were activated with 80dB beeps as a control. Electromyographic signals were recorded from the bilateral sternocleidomastoid (SCM), lower trapezius (LT), latissimus dorsi (LD), lumbar erector spinae and right anterior deltoid muscles and also from the right flexor and extensor carpi radialis muscles (ECR/FCR). In the subsequent processing the electromyographic time domain and frequency domain indicators were converted into a pre-motor reaction time, a time to muscle peak contraction, an activation latency, and APA or compensatory postural adjustment (CPA) amplitude of the tested muscles. These were compared among the different tasks and stimuli. In addition, the 114dB test tasks were classified as two different priming status as SCM + and SCM - according to whether the sternocleidomastoid muscle (SCM) was activated in advance. Results:After RST activation the pre-motor reaction time and the time to peak contraction of all of the muscles were significantly shortened in all of the tasks. The deltoid muscle reaction times in the SCM + , SCM - and control states were (106.89±43.78)ms, (136.78±48.74)ms and (168.60±73.17)ms, respectively, and those differences are significant. The APA amplitudes of the contralateral LT and ipsilateral LD were significantly greater than normal, but the timing of muscle activation onset and the APA/CPA amplitudes of the ECR/FCR were not affected. The latency in the anticipatory muscle activation of the ECR in the little finger grip task was significantly shorter than that in reaching. Conclusions:The extensor carpi radialis show task-specific early activation in fine tasks of the upper limbs with different difficulties. RST activation can lead to early starting of expected actions, accelerate muscle contraction and increase APA amplitude of some trunk muscles, but it has no significant effect on APA/CPA amplitudes in the forearm muscles.

Olfactory Gene Families in Scopula subpunctaria and Candidates for Type-II Sex Pheromone Detection.

Scopula subpunctaria, an abundant pest in tea gardens, produce type-II sex pheromone components, which are critical for its communicative and reproductive abilities; however, genes encoding the proteins involved in the detection of type-II sex pheromone components have rarely been documented in moths. In the present study, we sequenced the transcriptomes of the male and female S. subpunctaria antennae. A total of 150 candidate olfaction genes, comprising 58 odorant receptors (SsubORs), 26 ionotropic receptors (SsubIRs), 24 chemosensory proteins (SsubCSPs), 40 odorant-binding proteins (SsubOBPs), and 2 sensory neuron membrane proteins (SsubSNMPs) were identified in S. subpunctaria. Phylogenetic analysis, qPCR, and mRNA abundance analysis results suggested that SsubOR46 may be the Orco (non-traditional odorant receptor, a subfamily of ORs) of S. subpunctaria. SsubOR9, SsubOR53, and SsubOR55 belonged to the pheromone receptor (PR) clades which have a higher expression in male antennae. Interestingly, SsubOR44 was uniquely expressed in the antennae, with a higher expression in males than in females. SsubOBP25, SsubOBP27, and SsubOBP28 were clustered into the moth pheromone-binding protein (PBP) sub-family, and they were uniquely expressed in the antennae, with a higher expression in males than in females. SsubOBP19, a member of the GOBP2 group, was the most abundant OBP in the antennae. These findings indicate that these olfactory genes, comprising five candidate PRs, three candidate PBPs, and one candidate GOBP2, may be involved in type II sex pheromone detection. As well as these genes, most of the remaining SsubORs, and all of the SsubIRs, showed a considerably higher expression in the female antennae than in the male antennae. Many of these, including SsubOR40, SsubOR42, SsubOR43, and SsubIR26, were more abundant in female antennae. These olfactory and ionotropic receptors may be related to the detection of host plant volatiles. The results of this present study provide a basis for exploring the olfaction mechanisms in S. subpunctaria, with a focus on the genes involved in type II sex pheromones. The evolutionary analyses in our study provide new insights into the differentiation and evolution of lepidopteran PRs.

PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and still has a considerable impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, the primary responsible for the host immune response upon infection. Here we show the preclinical studies of a broad protective SARS-CoV-2 subunit vaccine developed from our Trimer Domain platform using the Delta spike protein, from antigen design to purification, vaccine evaluation and manufacturability. The prefusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. The immunogenicity studies demonstrated that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous virus challenge. The neutralizing antibodies induced by this vaccine display a cross-reactive capacity against the ancestral WA1 and Delta variants as well as different Omicron, including BA.5.2. The Trimer Domain platform was proven to be a key technology in the rapid production of the PF-D-Trimer vaccine and may be crucial to accelerate the development of updated versions of SARS-CoV-2 vaccines.

The reliability and validity of using a head-neck relocation test to assess cervical position sense / 中华物理医学与康复杂志

Objective:To observe the reliability and validity of using a head-neck relocation test (HRT) in assessing cervical position sense.Methods:A total of 62 subjects were recruited, including 32 with neck pain and 30 healthy subjects. All received two HRTs conducted by two independent assessors at a first session, and then they received another HRT 24 hours later administered by one of them. The joint position error (JPE) was measured in the four directions of cervical motion: flexion, extension, levorotation and dextrorotation. The intra- and inter-rater reliability was quantified in terms of intra-class correlation coefficients (ICCs) and the difference in JPE between the two groups was also determined for validity.Results:The intra- and inter-rater reliability for the HRT in the four directions had ICC values of 0.603-0.830 and 0.597-0.837 respectively. The corresponding standard error of measurement (SEM) values were 1.52-2.15cm and 1.69-2.09cm, while the minimal detectable change (MDC) values were 4.20-5.97cm and 4.69-5.79cm, respectively. The patients with neck pain had significantly larger JPE in cervical extension and right rotation compared to healthy individuals, on average. And their JPE for cervical extension had an area under the curve (AUC) of the receiver′s operating curve of 0.755.Conclusions:The HRT showed good intra- and inter-rater reliability in assessing cervical joint position sense. The JPE for cervical extension can be used to discriminate those with neck pain from healthy subjects.

Application value of Hisense computer-assisted surgery system three-dimensional reconstru-tion in precision treatment of pediatric liver tumors / 中华消化外科杂志

Objective:To investigate the application value of Hisense computer-assisted surgery system (CAS) three-dimensional reconstruction in the precision treatment of pediatric liver tumors.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 82 children with liver tumors who were admitted to Affiliated Hospital of Qingdao University from January 2013 to September 2021 were collected. There were 39 males and 43 females, aged 13(19)months. Children underwent upper abdominal dynamic enhanced computed tomography (CT) examination, and three-dimensional reconstruction was performed on CT images of arterial, equili-brium and venous phases with Hisense CAS. Surgical feasibility and scheme were evaluated and conducted based on the results of upper abdominal dynamic enhanced CT examination, and then revised according to three-dimensional reconstruction results of Hisense CAS. Observation indicators: (1) comparison of surgical scheme between two-dimensional enhanced CT images and three-dimensional reconstruction results of Hisense CAS; (2) intraoperative and postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination to detect postoperative compli-cations and residual liver compensation up to November 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were described as absolute numbers or percentages. Results:(1) Comparison of surgical scheme between two-dimensional CT images and three-dimensional reconstruction results of Hisense CAS. ① Based on the two-dimensional CT images, 42 cases of 82 children could undergo one-stage resection and 40 children could not. However, based on the three-dimensional reconstruction results of Hisense CAS, 48 cases of 82 children could undergo one-stage resection and 34 children could not. There were 6 children with one-stage resection feasibility based on the three-dimensional reconstruction results of Hisense CAS rather than the two-dimensional CT images. For the 34 children undergoing chemotherapy firstly, 31 cases had surgical feasibility after chemotherapy based on the two-dimensional CT images and 3 cases could not undergo surgery because of unapparent tumor regression or tumor surrounding impor-tant vessels. However, the 34 children had surgical feasibility after chemotherapy based on the three-dimensional reconstruction results of Hisense CAS. The revision rate of surgical feasibility was 11.0%(9/82) for the 82 children. ② Based on the two-dimensional CT images, 15 cases of 82 children underwent liver left lobectomy, 21 cases underwent liver right lobectomy, 7 cases underwent mesohepatectomy, 13 cases underwent extended left hemihepatectomy, 23 cases underwent extended right hemihepatectomy, 3 cases underwent segmental hepatectomy. However, based on the three-dimensional reconstruction results of Hisense CAS, 20 cases of 82 children underwent liver left lobectomy, 29 cases underwent liver right lobectomy, 7 cases underwent mesohepatectomy, 7 cases underwent extended left hemihepatectomy, 14 cases underwent extended right hemihepatectomy, 5 cases underwent segmental hepatectomy. The revision rate of surgical scheme was 36.6%(30/82) for the 82 children. (2) Intraoperative and postoperative situations. The operation time, volume of intraoperative blood loss, duration of postoperative hospital stay of the 82 children were (182±18)minutes, 20(10)mL, (10.2±1.9)days, respectively. (3) Follow-up. All the 82 children were followed up for 10 (range, 2?18)months. There was no obvious complication occurred to the 82 children after surgery, and the residual liver can satisfy the liver compensation of body. All the children survived well.Conclusion:Three-dimensional reconstruction of Hisense CAS is conducive to judging the surgical feasibility and formulation of accurate surgical plan of children with liver tumors.

Application of a computer-assisted surgery system in precision surgery of mediastinal tumors in children / 中华实用儿科临床杂志

Objective:To analyze and summarize the application and significance of the computer-assisted surgery system in precision surgery of mediastinal tumors in children.Methods:The clinical data of 54 children that underwent mediastinal tumor resection surgery in the Affiliated Hospital of Qingdao University from August 2008 to November 2021 were collected.According to whether the Hisense CAS computer-assisted surgery system was used before the operation, the patients were divided into three-dimensional (3D) reconstruction group (29 cases, 53.70%) and two-dimensional (2D) CT group (25 cases, 46.30%). The surgical indicators, postoperative hospital stay, and the incidence of surgical complications were compared between the two groups.The t-test, Mann- Whitney U test, χ2 test or Fisher′ s exact test were carried out for statistical analysis.Simulated surgery and actual surgery were compared for both 3D reconstruction and 2D CT groups. Results:There were no significant differences in gender, age, height, weight, maximum tumor diameter and tumor location between the 3D reconstruction group and 2D CT group (all P>0.05). The operation time of the 3D reconstruction group was [(125.14±41.37) min] was shorter than that of the 2D CT group [(149.24±44.53) min] ( P=0.044). The intraoperative blood loss in the 3D reconstruction group [15.00(13.50, 25.00) mL] was less than that in the 2D CT group [36.00(30.00, 75.00) mL] ( P<0.001). In addition, the indwelling time the closed thoracic drainage tube [4.00 (3.00, 5.50) d] and postoperative hospitalization days [(8.83±3.39) d] in the 3D reconstruction group were shorter than those in the 2D CT group [7.00(5.00, 11.50) d, (11.00±4.10) d] ( P=0.001, 0.038). No significant difference in postoperative complication rates was found between the 3D reconstruction group and 2D CT group ( P>0.05). The simulated operation was consistent with the actual operation in the 3D reconstruction group. Conclusions:3D reconstruction by the computer-assisted surgery system can truly reveal the anatomical relationship between tumors and surrounding organs and blood vessels, and improve the accuracy and safety of surgical resection of mediastinal tumors in children.

Transoral endoscopic resection of benign tumors in parapharyngeal space via medial pterygomandibular raphe approach / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the surgical methods and effects of transoral endoscopic resection of benign tumors in parapharyngeal space via medial pterygomandibular raphe approach. Methods: The clinical data of 23 patients who underwent resection of benign tumors in parapharyngeal space by endoscopic medial pterygomandibular raphe approach from January 2016 to July 2020 in the Department of Otorhinolaryngology Head and Neck Surgery, the Affiliated Hospital of Qingdao University were analyzed retrospectively. There were 14 males and 9 females with a median age of 43 years. The tumors were located in the anterior space of the styloid process in 13 cases and in the posterior space in 10 cases. The smallest tumor volume was 7.3 ml and the largest was 80.2 ml. The preoperative imaging features, the characteristics and risks of this approach in the operation were analyzed, and the feasible mode of operation was explored. Results: All patients completed the operation successfully. The intraoperative blood loss was 20 to 50 ml, with an average of 28.3 ml. The operation time was 40 to 110 min, with an average of 75.4 min. The incision length was 2 to 4 cm, with an average of 3.0 cm. The postoperative pain score was 2 to 4, with an average of 3.2. The postoperative hospital stay was 4 to 9 d, with an average of 6.7 d. Postoperative pathological diagnosis included pleomorphic adenoma (n=12), neurilemmoma (n=10) and basal cell adenoma (n=1). The patients were followed up for 6 to 60 months. There was no postoperative complication such as infection or serious bleeding, and there was no tumor recurrence after operation. Conclusion: Endoscopic resection of benign tumor in parapharyngeal space via medial pterygomandibular raphe approach is a safe, effective, and minimally invasive surgical method for the treatment of tumors in parapharyngeal space.

Pediatric blastic plasmacytoid dendritic cell neoplasm: report of four cases and review of literature.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with poor outcome. Four children with BPDCN treated at our hospital were enrolled. All the four cases presented with cutaneous lesions. Bone marrow and central nervous system was involved in 50% and 25% of patients, respectively. The whole exome sequencing analysis revealed that KMT2 family genes were the most frequently mutated (4/4, 100%), followed by IKZF2 (2/4, 50%). The point mutation p.D348N was found in three patients and one patient had p.C394Y mutation in the KMT2C gene. Translocation of KMT2A-MLLT3 was found in Case 2. Case 1 had complex karyotype, who was induced by acute myeloid leukemia-like regimens. Although he received allogeneic hematopoietic stem cell transplantation twice as well as CD123 chimeric antigen receptor T cell therapy, the disease still progressed and he died 37 months after diagnosis. The other three patients were treated with Interfant-99 protocol. They tolerated the therapy well without significant toxicities and now in complete remission so far with a median follow up time of 9 months. More studies are needed to address the question whether the complex karyotype and KMT2 family genes are the causes of the relapse and refractory in BPDCN.

Development of a scoliosis rehabilitation robot and a preliminary study of its effectiveness in treating coronal deformity / 中华物理医学与康复杂志

Objective:To explore the appropriate use of a self-developed scoliosis rehabilitation robot in treating adolescent idiopathic scoliosis (AIS), and also its safety and effectiveness.Methods:The scoliosis rehabilitation robot consists of a closed-loop pneumatic control system and multi-segment torso, pelvis and upper extremity fixation devices. It provides three-dimensional synchronous correction. Eighteen AIS subjects first received 30min of robot-assisted treatment using the maximum tolerable orthotic force. The angles of their spinal processes were evaluated using ultrasound before the treatment and after 30 seconds, 5 minutes and 30 minutes of treatment, then 5min later. In a second 30sec course of treatment the transverse orthotic force was 10%, 15%, 20%, 25%, and 30% of the patient′s body weight. Any adverse effects were observed and recorded.Results:The robot ran smoothly and could apply intelligent and precise correction. No severe adverse effects were reported. The mean correction of the spinal process angles showed a significant cumulative effect with treatment time, reaching 104% at 30min. The mean process angle correction increased with the applied force. Force at 25% of the patient′s weight produced an average correction of 104% in patients with mild AIS and 65% in those whose AIS was moderate.Conclusion:The scoliosis rehabilitation robot is safe and immediately effective. Setting the transverse force at 25% of a patient′s weight gives the best corrective effect with mild AIS. Moderate AIS requires more force.

Effect of adverse childhood experiences and DNA methylation on male sexual orientation / 中南大学学报(医学版)

The causes for male sexual orientation are complicated, which have not yet been clarified. Recent years have witnessed fruitful progress in the field of biology, while the impact of environment has received little attention. Adverse childhood experiences (ACEs), identified as a special environment in the early stage of development, can affect the individual phenotype by DNA methylation. Given the relationships among male sexual orientation, ACEs, and DNA methylation, as well as based on the existing theory, this article proposes the model "ACEs-DNA methylation-male sexual orientation"from the perspective of environment and epigenetics, aiming to provide a theoretical basis for future research.

Neurogenic pulmonary edema following acute stroke: The progress and perspective.

Neurogenic pulmonary edema (NPE) following acute stroke is an acute respiratory distress syndrome (ARDS) with clinical characteristics that include acute onset, apparent pulmonary interstitial fluid infiltration and rapid resolution. The pathological process of NPE centers on sympathetic stimulation and fulminant release of catecholamines, which cause contraction of resistance vessels. Elevated systemic resistance forces fluid into pulmonary circulation, while pulmonary circulation overload induces pulmonary capillary pressure that elevates, and in turn damages the alveolar capillary barrier. Damage to the alveolar capillary barrier leads to pulmonary ventilation disorder, blood perfusion disorder and oxygenation disorder. Eventually, NPE will cause post-stroke patients' prognosis to further deteriorate. At present, we lack specific biological diagnostic indicators and a meticulously unified diagnostic criterion, and this results in a situation in which many patients are not recognized quickly and/or diagnosed accurately. There are no drugs that are effective against NPE. Therefore, understanding how to diagnose NPE early by identifying the risk factors and how to apply appropriate treatment to avoid a deteriorating prognosis are important scientific goals. We will elaborate the progress of NPE after acute stroke in terms of its pathophysiological mechanisms, etiology, epidemiology, clinical diagnosis and early prediction, comprehensive treatment strategies, and novel drug development. We also propose our own thinking and prospects regarding NPE.

Cigarette smoke-initiated autoimmunity facilitates sensitisation to elastin-induced COPD-like pathologies in mice.

It is currently not understood whether cigarette smoke exposure facilitates sensitisation to self-antigens and whether ensuing auto-reactive T cells drive chronic obstructive pulmonary disease (COPD)-associated pathologies.To address this question, mice were exposed to cigarette smoke for 2 weeks. Following a 2-week period of rest, mice were challenged intratracheally with elastin for 3 days or 1 month. Rag1-/- , Mmp12-/- , and Il17a-/- mice and neutralising antibodies against active elastin fragments were used for mechanistic investigations. Human GVAPGVGVAPGV/HLA-A*02:01 tetramer was synthesised to assess the presence of elastin-specific T cells in patients with COPD.We observed that 2 weeks of cigarette smoke exposure induced an elastin-specific T cell response that led to neutrophilic airway inflammation and mucus hyperproduction following elastin recall challenge. Repeated elastin challenge for 1 month resulted in airway remodelling, lung function decline and airspace enlargement. Elastin-specific T cell recall responses were dose dependent and memory lasted for over 6 months. Adoptive T cell transfer and studies in T cells deficient Rag1-/- mice conclusively implicated T cells in these processes. Mechanistically, cigarette smoke exposure-induced elastin-specific T cell responses were matrix metalloproteinase (MMP)12-dependent, while the ensuing immune inflammatory processes were interleukin 17A-driven. Anti-elastin antibodies and T cells specific for elastin peptides were increased in patients with COPD.These data demonstrate that MMP12-generated elastin fragments serve as a self-antigen and drive the cigarette smoke-induced autoimmune processes in mice that result in a bronchitis-like phenotype and airspace enlargement. The study provides proof of concept of cigarette smoke-induced autoimmune processes and may serve as a novel mouse model of COPD.

Detection of the epidemic of the H3N8 subtype of the equine influenza virus in large-scale donkey farms.

To monitor the occurrence of equine influenza in large-scale donkey farms in Liaocheng City, Shandong Province, serological investigation and sequence analysis of HA/M protein gene of equine influenza virus (EIV) were carried out. Samples (n = 65) of the lung and nasal swab were collected in six different large-scale donkey farms and detected with RT-PCR for HA and M protein gene. The homology and evolution of HA and M genes were analysed with known sequences. Antibody titres of serum samples (n = 120, unvaccinated) level was determined by the HI test. The average seropositive rate was 32.5% (39/120) with great diversity among different populations. The positive rate of EIV HA/M protein gene was 21.5% (14/65) by RT-PCR. The equine influenza H3N8 virus was confirmed by gene sequencing, and the homology of the sequence was 99.77% with isolates from Northeast China (equine/heilongjiang/1/2010), consistent with the input of donkeys. This suggested that EIV has become an important threat to large-scale donkey farms in Liaocheng and threats from the input area must be vigilant.

Patterns of Cancer-Related Risk Behaviors Among Construction Workers in Hong Kong: A Latent Class Analysis Approach

Background@#Hong Kong's construction industry currently faces a manpower crisis. Blue-collar workers are a disadvantaged group and suffer higher levels of chronic diseases, for example, cancer, than the wider population. Cancer risk factors are likely to cluster together. We documented prevalence of cancer-associated lifestyle risk behaviors and their correlates among Hong Kong construction workers. @*Methods@#Data were collected from workers at 37 railway-related construction worksites throughout Hong Kong during May 2014. Tobacco use, alcohol consumption, unbalanced nutrition intake, and physical inactivity were included in the analysis. Latent class analysis and multivariable logistic regression were performed to identify the patterns of risk behaviors related to cancer, as well as their impact factors among construction workers in Hong Kong. @*Results@#Overall, 1,443 workers participated. Latent class analysis identified four different behavioral classes in the sample. Fully adjusted multiple logistic regression identified age, gender, years of Hong Kong residency, ethnicity, educational level, and living status differentiated behavioral classes. @*Conclusion@#High levels of lifestyle-related cancer-risk behaviors were found in most of the Hong Kong construction workers studied. The present study contributes to understanding how cancer-related lifestyle risk behaviors cluster among construction workers and relative impact factors of risk behaviors. It is essential to tailor health behavior interventions focused on multiple risk behaviors among different groups for further enlarging the effects on cancer prevention.

Reversal of Social Recognition Deficit in Adult Mice with MECP2 Duplication via Normalization of MeCP2 in the Medial Prefrontal Cortex / 神经科学通报·英文版

Methyl-CpG binding protein 2 (MeCP2) is a basic nuclear protein involved in the regulation of gene expression and microRNA processing. Duplication of MECP2-containing genomic segments causes MECP2 duplication syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, motor dysfunction, heightened anxiety, epilepsy, autistic phenotypes, and early death. Reversal of the abnormal phenotypes in adult mice with MECP2 duplication (MECP2-TG) by normalizing the MeCP2 levels across the whole brain has been demonstrated. However, whether different brain areas or neural circuits contribute to different aspects of the behavioral deficits is still unknown. Here, we found that MECP2-TG mice showed a significant social recognition deficit, and were prone to display aversive-like behaviors, including heightened anxiety-like behaviors and a fear generalization phenotype. In addition, reduced locomotor activity was observed in MECP2-TG mice. However, appetitive behaviors and learning and memory were comparable in MECP2-TG and wild-type mice. Functional magnetic resonance imaging illustrated that the differences between MECP2-TG and wild-type mice were mainly concentrated in brain areas regulating emotion and social behaviors. We used the CRISPR-Cas9 method to restore normal MeCP2 levels in the medial prefrontal cortex (mPFC) and bed nuclei of the stria terminalis (BST) of adult MECP2-TG mice, and found that normalization of MeCP2 levels in the mPFC but not in the BST reversed the social recognition deficit. These data indicate that the mPFC is responsible for the social recognition deficit in the transgenic mice, and provide new insight into potential therapies for MECP2 duplication syndrome.