PD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression.

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.

Single-shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad, durable and protective systemic and mucosal immunity in mice.

Current coronavirus disease 2019 vaccines face limitations including waning immunity, immune escape by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, limited cellular response, and poor mucosal immunity. We engineered a Clec9A-receptor binding domain (RBD) antibody construct that delivers the SARS-CoV-2 RBD to conventional type 1 dendritic cells. Compared with non-targeting approaches, single dose immunization in mice with Clec9A-RBD induced far higher RBD-specific antibody titers that were sustained for up to 21 months after vaccination. Uniquely, increasing neutralizing and antibody-dependent cytotoxicity activities across the sarbecovirus family was observed, suggesting antibody affinity maturation over time. Consistently and remarkably, RBD-specific follicular T helper cells and germinal center B cells persisted up to 12 months after immunization. Furthermore, Clec9A-RBD immunization induced a durable mono- and poly-functional T-helper 1-biased cellular response that was strongly cross-reactive against SARS-CoV-2 variants of concern, including Omicron subvariants, and with a robust CD8+ T cell signature. Uniquely, Clec9A-RBD single-shot systemic immunization effectively primed RBD-specific cellular and humoral immunity in lung and resulted in significant protection against homologous SARS-CoV-2 challenge as evidenced by limited body weight loss and approximately 2 log10 decrease in lung viral loads compared with non-immunized controls. Therefore, Clec9A-RBD immunization has the potential to trigger robust and sustained, systemic and mucosal protective immunity against rapidly evolving SARS-CoV2 variants.

Mechanically robust and personalized silk fibroin-magnesium composite scaffolds with water-responsive shape-memory for irregular bone regeneration.

The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.

Risk factors for cerebral edema following aneurysm clipping in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVES: To investigate the factors that contribute to the development of cerebral edema after aneurysm clipping in individuals with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A total of 232 patients with aSAH caused by rupture and treated with aneurysm clipping were included in the retrospective analysis of clinical data. Postoperatively, the participants were categorized into two groups based on the presence or absence of cerebral edema: a complication group (n=33) and a non-complication group (n=199).A comparison was made between the overall data of the 2 groups. RESULTS: In the complication group, there were higher proportions of patients experiencing recurrent bleeding, aneurysm in the posterior circulation, Fisher grade III-IV, World Federation of Neurosurgical Societies (WFNS) grade II, Hunt-Hess grade III-IV, concomitant hypertension, duration from onset to operation ≥12 h, and concomitant hematoma compared to the non-complication group (p<0.05). Cerebral edema after aneurysm clipping was associated with several risk factors including repeated bleeding, aneurysm in the back of the brain, Fisher grade III-IV, WFNS grade II, Hunt-Hess grade III-IV, simultaneous high blood pressure and hematoma, and a duration of at least 12 hours from the start of symptoms to the surgical procedure (p<0.05). CONCLUSION: In patients with aSAH, the risk of cerebral edema after aneurysm clipping is increased by recurrent bleeding, aneurysm in the posterior circulation, Fisher grade III-IV, WFNS grade II, Hunt-Hess grade III-IV, concomitant hypertension and hematoma, and duration of ≥12 h from onset to operation.

In-situ synthesis Fe3C@C/rGO as matrix for high performance lithium-sulfur batteries at room and low temperatures.

People have been focusing on how to improve the specific capacity and cycling stability of lithium-sulfur batteries at room temperature, however, on some special occasions such as cold cities and aerospace fields, the operating temperature is low, which dramatically hinders the performance of batteries. Here, we report an iron carbide (Fe3C)/rGO composite as electrode host, the Fe3C nanoparticles in the composite have strong adsorption and high catalytic ability for polysulfide. The rGO makes the distribution of Fe3C nanoparticles more disperse, and this specific structure makes the deposition of Li2S more uniform. Therefore, it realizes the rapid transformation and high performance of lithium-sulfur batteries at both room and low temperatures. At room temperature, after 100 cycles at 1C current density, the reversible specific capacity of the battery can be stabilized at 889 ± 7.1 mAh/g. Even at -40 °C, in the first cycle battery still emits 542.9 ± 3.7 mAh/g specific capacity. This broadens the operating temperature for lithium-sulfur batteries and also provides a new idea for the selection of host materials for sulfur in low-temperature lithium-sulfur batteries.

Bouncing Dynamics of Drops' Successive Off-Center Impact.

Bouncing dynamics of a trailing drop off-center impacting a leading drop with varying time intervals and Weber numbers are investigated experimentally. Whether the trailing drop impacts during the spreading or receding process of the leading drop is determined by the time interval. For a short time interval of 0.15 ≤ Δt* ≤ 0.66, the trailing drop impacts during the spreading of the leading drop, and the drops completely coalesce and rebound; for a large time interval of 0.66 < Δt* ≤ 2.21, the trailing drop impacts during the receding process, and the drops partially coalesce and rebound. Whether the trailing drop directly impacts the surface or the liquid film of the leading drop is determined by the Weber number. The trailing drop impacts the surface directly at moderate Weber numbers of 16.22 ≤ We ≤ 45.42, while it impacts the liquid film at large Weber numbers of 45.42 < We ≤ 64.88. Intriguingly, when the trailing drop impacts the surface directly or the receding liquid film, the contact time increases linearly with the time interval but independent of the Weber number; when the trailing drop impacts the spreading liquid film, the contact time suddenly increases, showing that the force of the liquid film of the leading drop inhibits the receding of the trailing drop. Finally, a theoretical model of the contact time for the drops is established, which is suitable for different impact scenarios of the successive off-center impact. This study provides a quantitative relationship to calculate the contact time of drops successively impacting a superhydrophobic surface, facilitating the design of anti-icing surfaces.

Machine learning models reveal the critical role of nighttime systolic blood pressure in predicting functional outcome for acute ischemic stroke after endovascular thrombectomy.

Background: Blood pressure (BP) is a key factor for the clinical outcomes of acute ischemic stroke (AIS) receiving endovascular thrombectomy (EVT). However, the effect of the circadian pattern of BP on functional outcome is unclear. Methods: This multicenter, retrospective, observational study was conducted from 2016 to 2023 at three hospitals in China (ChiCTR2300077202). A total of 407 patients who underwent endovascular thrombectomy (EVT) and continuous 24-h BP monitoring were included. Two hundred forty-one cases from Beijing Hospital were allocated to the development group, while 166 cases from Peking University Shenzhen Hospital and Hainan General Hospital were used for external validation. Postoperative systolic BP (SBP) included daytime SBP, nighttime SBP, and 24-h average SBP. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), Boruta were used to screen for potential features associated with functional dependence defined as 3-month modified Rankin scale (mRS) score ≥ 3. Nine algorithms were applied for model construction and evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: Three hundred twenty-eight of 407 (80.6%) patients achieved successful recanalization and 182 patients (44.7%) were functional independent. NIHSS at onset, modified cerebral infarction thrombolysis grade, atrial fibrillation, coronary atherosclerotic heart disease, hypertension were identified as prognostic factors by the intersection of three algorithms to construct the baseline model. Compared to daytime SBP and 24-h SBP models, the AUC of baseline + nighttime SBP showed the highest AUC in all algorithms. The XGboost model performed the best among all the algorithms. ROC results showed an AUC of 0.841 in the development set and an AUC of 0.752 in the validation set for the baseline plus nighttime SBP model, with a brier score of 0.198. Conclusion: This study firstly explored the association between circadian BP patterns with functional outcome for AIS. Nighttime SBP may provide more clinical information regarding the prognosis of patients with AIS after EVT.

Machine learning for predicting liver and/or lung metastasis in colorectal cancer: A retrospective study based on the SEER database.

OBJECTIVE: This study aims to establish a machine learning (ML) model for predicting the risk of liver and/or lung metastasis in colorectal cancer (CRC). METHODS: Using the National Institutes of Health (NIH)'s Surveillance, Epidemiology, and End Results (SEER) database, a total of 51265 patients with pathological diagnosis of colorectal cancer from 2010 to 2015 were extracted for model development. On this basis, We have established 7 machine learning algorithm models. Evaluate the model based on accuracy, and AUC of receiver operating characteristics (ROC) and explain the relationship between clinical pathological features and target variables based on the best model. We validated the model among 196 colorectal cancer patients in Beijing Electric Power Hospital of Capital Medical University of China to evaluate its performance and universality. Finally, we have developed a network-based calculator using the best model to predict the risk of liver and/or lung metastasis in colorectal cancer patients. RESULTS: 51265 patients were enrolled in the study, of which 7864 (15.3 %) had distant liver and/or lung metastasis. RF had the best predictive ability, In the internal test set, with an accuracy of 0.895, AUC of 0.956, and AUPR of 0.896. In addition, the RF model was evaluated in the external validation set with an accuracy of 0.913, AUC of 0.912, and AUPR of 0.611. CONCLUSION: In this study, we constructed an RF algorithm mode to predict the risk of colorectal liver and/or lung metastasis, to assist doctors in making clinical decisions.

Reverse causation between multiple sclerosis and psoriasis: a genetic correlation and Mendelian randomization study.

Observational studies have found a potential bidirectional positive association between multiple sclerosis and psoriasis, but these studies are susceptible to confounding factors. We examined the directionality of causation using Mendelian randomization and estimated the genetic correlation using the linkage disequilibrium score. We performed Mendelian randomization analysis using large-scale genome-wide association studies datasets from the International Multiple Sclerosis Genetics Consortium (IMSGC, 115,803 individuals of European ancestry) and FinnGen (252,323 individuals of European ancestry). We selected several Mendelian randomization methods including causal analysis using summary effect (CAUSE), inverse variance-weighted (IVW), and pleiotropy-robust methods. According to CAUSE and IVW the genetic liability to MS reduces the risk of psoriasis (CAUSE odds ratio [OR] 0.93, p = 0.045; IVW OR 0.93, p = 2.51 × 10-20), and vice versa (CAUSE OR 0.72, p = 0.001; IVW OR 0.71, p = 4.80 × 10-26). Pleiotropy-robust methods show the same results, with all p-values < 0.05. The linkage disequilibrium score showed no genetic correlation between psoriasis and MS (rg = - 0.071, p = 0.2852). In summary, there is genetic evidence that MS reduces the risk of psoriasis, and vice versa.

Identifying key risk factors for acute compartment syndrome in tibial diaphysis fracture patients.

Acute compartment syndrome (ACS) is a severe orthopedic issue that, if left untreated, can result in lasting nerve and muscle damage or even necessitate amputation. The association between admission laboratory blood test indicators and the occurrence of ACS in patients with tibial diaphysis fractures is currently a subject of debate. The objective of this research was to identify the contributing factors for ACS in individuals suffering from tibial diaphysis fractures. In this retrospective study, we collected data on a total of 705 individuals from our hospital, comprising 86 ACS patients and 619 non-ACS patients with tibial diaphysis fractures. These participants were categorized into two distinct groups: the ACS group and the non-ACS group. Despite the inherent limitations associated with retrospective analyses, such as potential biases in data collection and interpretation, we conducted a comprehensive analysis of demographics, comorbidities, and admission lab results. Our analytical approach included univariate analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis techniques, aiming to mitigate these limitations and provide robust findings. The statistical analysis revealed several predictors of ACS, including gender (p = 0.011, OR = 3.200), crush injuries (p = 0.004, OR = 4.622), lactic dehydrogenase (LDH) levels (p < 0.001, OR = 1.003), and white blood cell (WBC) count (p < 0.001, OR = 1.246). Interestingly, the study also found that certain factors, such as falls on the same level (p = 0.007, OR = 0.334) and cholinesterase (CHE) levels (p < 0.001, OR = 0.721), seem to provide a degree of protection against ACS. In order to better predict ACS, the ROC curve analysis was employed, which determined threshold values for LDH and WBC. The established cut-off points were set at 266.26 U/L for LDH and 11.7 × 109 cells per liter for WBC, respectively. Our research has successfully pinpointed gender, crush injuries, LDH levels, and white blood cell (WBC) count as crucial risk factors for the development of ACS in patients experiencing tibial diaphysis fractures. Furthermore, by establishing the cut-off values for LDH and WBC, we have facilitated a more personalized assessment of ACS risk, enabling clinical doctors to implement targeted early interventions and optimize patient outcomes.

RNAi-mediated silencing of the neverland gene inhibits molting in the migratory locust, Locusta migratoria.

7-dehydrocholesterol (7-DHC) is a key intermediate product used for biosynthesis of molting hormone. This is achieved through a series of hydroxylation reactions catalyzed by the Halloween family of cytochrome P450s. Neverland is an enzyme catalyzes the first reaction of the ecdysteroidogenic pathway, which converts dietary cholesterol into 7-DHC. However, research on the physiological function of neverland in orthopteran insects is lacking. In this study, neverland from Locusta migratoria (LmNvd) was cloned and analyzed. LmNvd was mainly expressed in the prothoracic gland and highly expressed on days 6 and 7 of fifth instar nymphs. RNAi-mediated silencing of LmNvd resulted in serious molting delays and abnormal phenotypes, which could be rescued by 7-DHC and 20-hydroxyecdysone supplementation. Hematoxylin and eosin staining results showed that RNAi-mediated silencing of LmNvd disturbed the molting process by both promoting the synthesis of new cuticle and suppressing the degradation of the old cuticle. Quantitative real-time PCR results suggested that the mRNA expression of E75 early gene and chitinase 5 gene decreased and that of chitin synthase 1 gene was markedly upregulated after knockdown of LmNvd. Our results suggest that LmNvd participates in the biosynthesis process of molting hormone, which is involved in regulating chitin synthesis and degradation in molting cycles.

BMSC-Derived Exosomes Attenuate Rat Osteoarthritis by Regulating Macrophage Polarization through PINK1/Parkin Signaling Pathway.

OBJECTIVE: Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may modulate the M1/M2 polarization of macrophages during osteoarthritis (OA). However, the underlying mechanisms of BMSC-Exos in this process still need to be elucidated. In this study, we explored the role of BMSC-Exos in the polarization of macrophages in vitro and the OA rats in vivo. METHODS: The effects of BMSC-Exos on RAW264.7 cells were determined, including the production of reactive oxygen species (ROS) and the protein expression of Akt, PINK1, and Parkin. We prepared an OA model by resecting the anterior cruciate ligament and medial meniscus of Sprague-Dawley (SD) rats. Hematoxylin-eosin (H&E) and safranin O-fast green staining, immunohistochemistry and immunofluorescence analyses, and the examination of interleukin 6 (IL-6), interleukin 1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10) were performed to assess changes in cartilage and synovium. RESULTS: BMSC-Exos inhibited mitochondrial membrane damage, ROS production, and the protein expression of PINK1 and Parkin. Akt phosphorylation was downregulated under lipopolysaccharide (LPS) induction but significantly recovered after treatment with BMSC-Exos. BMSC-Exos alleviated cartilage damage, inhibited M1 polarization, and promoted M2 polarization in the synovium in OA rats. The expression of PINK1 and Parkin in the synovium and the levels of IL-6, IL-1ß, and TNF-α in the serum decreased, but the level of IL-10 increased when BMSC-Exos were used in OA rats. CONCLUSION: BMSC-Exos ameliorate OA development by regulating synovial macrophage polarization, and one of the underlying mechanisms may be through inhibiting PINK1/Parkin signaling.

[A Real-World Single-Center Study of Adult Hodgkin's Lymphoma].

OBJECTIVE: To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). METHODS: A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, ß2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. RESULTS: In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. CONCLUSIONS: The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

Regulatory mechanism and molecular genetic dissection of rice (Oryza sativa L.) grain size.

With the sharp increase of the global population, adequate food supply is a great challenge. Grain size is an essential determinant of rice yield and quality. It is a typical quantitative trait controlled by multiple genes. In this paper, we summarized the quantitative trait loci (QTL) that have been molecularly characterized and provided a comprehensive summary of the regulation mechanism and genetic pathways of rice grain size. These pathways include the ubiquitin-proteasome system, G-protein, mitogen-activated protein kinase, phytohormone, transcriptional factors, abiotic stress. In addition, we discuss the possible application of advanced molecular biology methods and reasonable breeding strategies, and prospective on the development of high-yielding and high-quality rice varieties using molecular biology techniques.

Achieving ultrahigh uranium/vanadium selectivity of poly(amidoxime) via coupling MXene-enabled strong intermolecular interaction and separated photothermal interface.

Poly(amidoxime) (PAO) has been recognized as the most potential candidate for extracting uranium from seawater, owing to its merits of outstanding uranium affinity, low cost, and large-scale production. Despite remarkable achievements, existing PAO sorbents suffer from unsatisfactory uranium extraction efficiency and selectivity, as imposed by the inherently sluggish uranium adsorption kinetics and inevitable spatial configuration transition of amidoxime, which diminishes uranium affinity. Herein, we discover a facile and integrated design to elaborate a PAO/MXene nanocomposite that delivers ultrahigh and durable uranium/vanadium (U/V) selectivity. The key to our design lies in harnessing MXene-enabled strong intermolecular interactions to PAO to minimize the spatial configuration transition of amidoxime and stabilizing its superior uranium affinity, as well as creating a separated photothermal interface to maximize temperature-strengthened affinity for uranium over vanadium. Such a synergetic effect allows the nanocomposite to acquire over a 4-fold improvement in U/V selectivity compared to that of pure PAO as well as an unprecedented distribution coefficient of uranium compared to most state-of-the-art sorbents. We further demonstrate that our nanocomposite exhibits durable U/V selectivity with negligible attenuation and good antibacterial ability even in long-term operation. The design concept and extraordinary performance in this study bring PAO-based sorbents a step closer to practical uranium extraction from seawater.

Learning curves for itinerant nurses to master the operation skill of Ti-robot-assisted spinal surgery equipment by CUSUM analysis: A pilot study.

This study aimed to investigate the minimum number of operations required for itinerant nurses in the operating room to master the skills needed to operate the Ti-robot-assisted spinal surgery equipment. Additionally, we aimed to provide a corresponding basis for the development of qualification admission criteria and skill training for nurses who cooperate with this type of surgery. Nine operating room itinerant nurses independently performed Ti-robot equipment simulations using a spine model as a tool, with 16 operations per trainee. Four evaluation indices were recorded: time spent on equipment preparation and line connections, time spent on image acquisition and transmission, time spent on surgical spine screw placement planning, and time spent on robot arm operation. Individual and general learning curves were plotted using cumulative sum analysis. The number of cases in which the slope of the individual learning curves began to decrease was 3-11 cases, and the number of cases in which the slope of the general learning curve began to decrease was 8 cases. The numbers of cases in which the learning curves began to decrease in the four phases were the 5th, 8th, 11th, and 3rd cases. Itinerant nurses required at least eight cases to master the equipment operation skills of Ti-robot-assisted spinal surgery. Among the four phases, the image acquisition and transmission phases and the surgical spine screw placement planning phase were the most difficult and must be emphasized in future training.

Study on the Low-Velocity Impact Response and Damage Mechanisms of Thermoplastic Composites.

A comparative experimental and numerical study of the impact behaviour of carbon-fiber-reinforced thermoplastic (TP) and thermoset (TS) composites has been carried out. On the one hand, low velocity impact (LVI) tests were performed on TP and TS composites with different lay-up sequences at different energy levels, and the damage modes and microscopic damage mechanisms after impact were investigated using macroscale inspection, C-scan inspection, and X-ray-computed tomography. The comparative results show that the initial damage valve force under LVI depends not only on the material, but also on the layup sequence. The initial valve force of the P2 soft layer with lower stiffness is about 11% lower than that of the P1 quasi-isotropic layer under the same material, while the initial valve force of thermoplastic composites is about 28% lower than that of thermoset composites under the same stacking order. Under the same stacking order and impact energy level, the damage area and depth of TP composites are smaller than those of TS composites; while under the same material and impact energy level, the indentation depth of P2 plies is greater than that of P1 plies, and the damage area of P2 plies is smaller than that of P1 plies, but the change of thermoplastic composites is not as obvious as that of thermoset composites. This indicates that TP composites have a higher initial damage threshold energy and impact resistance at the same lay-up order, while increasing the lay-up ratio of the same material by 45° improves the impact resistance of the structure. In addition, a damage model based on continuum damage mechanics (CDM) was developed to predict different damage modes of thermoplastic composites during low velocity impact, and the analytical results were compared with the experimental results. At an impact energy of 4.45 J/mm, the error of the initial damage valve force is 5.26% and the error of the maximum impact force is 4.36%. The simulated impact energy and impact velocity curves agree with the experimental results, indicating that the finite element model has good reliability.

Presence of Spontaneous Nystagmus, Benign Paroxysmal Positional Vertigo, and Tumarkin Fall in Patients With Primary Headache and Their Responses to Caloric and Video Head Impulse Tests.

Background: Migraine, vestibular migraine (VM) and tension-type headache (TTH) are the most common disorders in dizziness and headache clinics, associated with dizziness or vertigo and postural imbalance, causing a substantial burden on the individual and the society. The objective of this research was to examine the presence of spontaneous nystagmus, comorbidity of benign paroxysmal positional vertigo (BPPV), and Tumarkin fall in patients; additionally, the study focused on assessing the patients' responses to bithermal caloric irrigation and video head impulse test (vHIT). Methods: Consecutive patients diagnosed with migraine, VM, and TTH according to the International Classification of Headache Disorders, third edition (beta version (ICHD-3ß)), who were referred to Dizziness and Headache Clinic were enrolled. BPPV and Tumarkin fall were assessed by questionnaires. The presence of BPPV was further evaluated through Dix-Hallpike or head roll maneuver, while spontaneous nystagmus was monitored using video-oculography during interictal period. Lastly, patients' responses to bithermal caloric irrigation and vHIT were analyzed. Results: There was a significantly higher incidence of spontaneous nystagmus in VM compared to both migraine and TTH. The drop attack episodes were slightly more frequent in VM than in TTH and migraine, though not statistically significant. The prevalence of BPPV was significantly higher in VM than in migraine and TTH. Unilateral vestibular paresis was more common in the VM group than in migraine and TTH. There was profound unilateral weakness (UW) in VM patients than in migraine, but no significant difference was found between VM and TTH. In VM, the percentage of saccades along with reduced vHIT gain was significantly higher than in migraine. Lastly, the percentage of abnormal response in vHIT was significantly lower than the percentage of abnormal UW in caloric irrigation across all groups. Conclusions: In VM patients, the prevalences of decompensated peripheral damage and BPPV were higher than in migraine and TTH patients as disclosed by the presence of peripheral spontaneous nystagmus and abnormal vHIT during the interictal period. Our findings suggest that the peripheral vestibular system acts as a significant mechanism in the pathogenesis of VM, and it might also be involved in migraine and TTH cases without vertigo symptoms.

Comparative and phylogenetic analysis of the complete chloroplast genomes of ten Pittosporum species from East Asia.

Pittosporum (Pittosporaceae) is famous as the ornamental and medical values, which is distributed tropical and subtropical regions of Eastern Hemisphere. The few phylogenetic studies have included samples from the Pacific Island, but the phylogenetic relationships of Asian species has not been studied. Here, the complete chloroplast (cp) genomes of ten Pittosporum species from East Asia were first sequenced and compared with those of the published species of this genus. Our results indicated that cp genomes of these species had a typical and conserved quadripartite structure. 131 genes were identical in order and orientation and no changes of inverted repeat (IR) occurred. However, the comparative analysis of cp genomes suggested that sequence divergence mainly appeared in non-coding or intergenic regions, in which several divergence hotspots were identified. By contrast, protein-coding genes showed the lowest variance under strong purifying selection. Phylogenetic analysis based on the cp genome sequences showed that the tested Pittosporum species were clustered into two major clades, in which the Asian species formed Clade I and the remaining species from Australia and New Zealand formed Clade II with high support values, which was consistent with the results of ITS data with low support values. These results suggested that cp genome is a robust phylogenetic indicator for deep nodes in the phylogeny of Pittosporum. Meanwhile, these results will provide the valuable information to better understand the phylogeny and biogeography of Pittosporum.

Direct vagus nerve stimulation: A new tool to control allergic airway inflammation through α7 nicotinic acetylcholine receptor.

BACKGROUND AND PURPOSE: Asthma is characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. The use of nicotinic agents to mimic the cholinergic anti-inflammatory pathway (CAP) controls experimental asthma. Yet, the effects of vagus nerve stimulation (VNS)-induced CAP on allergic inflammation remain unknown. EXPERIMENTAL APPROACH: BALB/c mice were sensitized and challenged with house dust mite (HDM) extract and treated with active VNS (5 Hz, 0.5 ms, 0.05-1 mA). Bronchoalveolar lavage (BAL) fluid was assessed for total and differential cell counts and cytokine levels. Lungs were examined by histopathology and electron microscopy. KEY RESULTS: In the HDM mouse asthma model, VNS at intensities equal to or above 0.1 mA (VNS 0.1) but not sham VNS reduced BAL fluid differential cell counts and alveolar macrophages expressing α7 nicotinic receptors (α7nAChR), goblet cell hyperplasia, and collagen deposition. Besides, VNS 0.1 also abated HDM-induced elevation of type 2 cytokines IL-4 and IL-5 and was found to block the phosphorylation of transcription factor STAT6 and expression level of IRF4 in total lung lysates. Finally, VNS 0.1 abrogated methacholine-induced hyperresponsiveness in asthma mice. Prior administration of α-bungarotoxin, a specific inhibitor of α7nAChR, but not propranolol, a specific inhibitor of ß2-adrenoceptors, abolished the therapeutic effects of VNS 0.1. CONCLUSION AND IMPLICATIONS: Our data revealed the protective effects of VNS on various clinical features in allergic airway inflammation model. VNS, a clinically approved therapy for depression and epilepsy, appears to be a promising new strategy for controlling allergic asthma.