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Background: There is increasing evidence for adverse health effects associated with aircraft-emitted particulate matter (PM) exposures, which are largely in the ultrafine (PM0.1) size fraction, but no previous study has examined neurodevelopmental outcomes. Objective: To assess associations between maternal exposure to aircraft ultrafine particles (UFP) during pregnancy and offspring autism spectrum disorder (ASD) diagnosis. Methods: This large, representative cohort study included 370,723 singletons born in a single healthcare system. Demographic data, maternal health information, and child’s ASD diagnosis by age 5 were extracted from electronic medical records. Aircraft exposure estimates for PM0.1 were generated by the University of California Davis/California Institute of Technology Source Oriented Chemical Transport model. Cox proportional hazard models were used to assess associations between maternal exposure to aircraft PM0·1 in pregnancy and ASD diagnosis, controlling for covariates. Results: Over the course of follow-up, 4,554 children (1.4 %) were diagnosed with ASD. Increased risk of ASD was associated with maternal exposure to aircraft PM0.1 [hazard ratio, HR: 1.02, (95 % confidence interval (CI): 1.01–1.03) per IQR = 0.02 µg/m3 increase during pregnancy. Associations were robust to adjustment for total PM0.1 and fine particulate matter (PM2.5), near-roadway air pollution, and other covariates. Noise adjustment modestly attenuated estimates of UFP effects, which remained statistically significant. Discussion: The results strengthen the emerging evidence that maternal particulate matter exposure during pregnancy is associated with offspring ASD diagnosis and identify aircraft-derived PM0.1 as novel targets for further study and potential regulation.

Bioelectric field is a stimulated force to degrade xenobiotic pollutants in soils. However, the effect of bioelectric field on microplastics (MPs) aging is unclear. The degradation behavior of polyvinyl chloride (PVC), polyethylene (PE) and polylactic acid (PLA) was investigated in an agricultural soil microbial electrochemical system in which bioelectric field was generated in-situ by native microbes. Based on the density function theory, the energy gaps between the highest and the lowest occupied molecular orbitals of the three polymers with periodic structure were 4.20, 7.24 and 10.09 eV respectively, and further decreased under the electric field, indicating the higher hydrolysis potential of PLA. Meanwhile, the mass loss of PLA in the closed-circuit group (CC) was the highest on day 120, reaching 8.94%, which was 3.01–3.54 times of that without bioelectric field stimulation. This was mainly due to the enrichment of plastic-degrading bacteria and a robust co-occurrence network as the deterministic assembly process, e.g., the abundance of potential plastic-degrading bacteria on the surface of PLA and PVC in the CC increased by 1.92 and 1.30 times, respectively, compared to the open-circuit group. In terms of functional genes, the xenobiotic biodegradation and metabolism capacity of plasticsphere in the CC were stronger than that in soil, and determined by the bioaccessibility of soil nitrogen and carbon. Overall, this study explored the promoting effect of bioelectric field on the degradation of MPs and reveled the mechanism from quantum chemical calculations and microbial community analysis, which provides a novel perception to the in-situ degradation of MPs.

Objective: Obesity in laboratory rodents is generally induced by feeding them a high fat diet (HFD). This model does not permit separation of the impact of the HFD from the resultant obesity on metabolic defects such as impaired glucose homeostasis. In Brandt's voles we have previously shown that exposure to long photoperiod (LD: 16L: 8D) induces obesity even when they are fed a low fat diet. We show here that these voles are largely resistant to HFD. This model therefore permits some separation of the effects of HFD and obesity on glucose homeostasis. The objective was therefore to use this model to assess if glucose homeostasis is more related to diet or obesity Methods: Male voles, which were 35 days old and born in LD, were exposed to SD and a low fat diet for 70 days. We then randomly separated the animals into 4 groups for another 63 days: SL (short day and low fat diet: n = 19) group; SH (short day and high-fat diet, n = 20) group; LL (long day and low-fat diet, n = 20) group; LH (long day and high-fat diet, n = 18) group. Glucose tolerance tests (GTT) were performed after treatment for 56 days, and body compositions of the voles were quantified at the end by dissection. Results: Consistent with our previous work LD voles were more obese than SD voles. Although total body weight was independent of dietary fat content, HFD did have an effect on fat storage. Photoperiod induced obesity had no effect on glucose homeostasis, and the fat content in both the liver and muscle. In contrast, HFD induced adiposity was linked with elevated fat deposition in muscle (but not in liver) and led to impaired glucose tolerance. Conclusions: The contrasting effects of diet and photoperiod were consistent with the predictions of the ‘lipotoxicity hypothesis’. This may contribute to our understanding of why some human individuals are able to be obese yet remain metabolically healthy.

The foamed warm mix asphalt (FWMA) has been widely used as a sustainable construction technique in pavement engineering, yet has not yet been fully studied for its aging performance or durability. Here we aim to examine and evaluate the performance variation characteristic of FWMA compared with conventional hot mix asphalt (HMA) under long-term service conditions. The performance evolution of FWMA core samples drilled from four highways was compared to that of ordinary HMA, which was simultaneously constructed. Fourier transform infrared (FTIR), dynamic shear rheology (DSR), and bending beam rheometer (BBR) tests were respectively performed to evaluate the aging degree, high-temperature, and low-temperature rheological characteristics. The results demonstrated that the aging resistance of foamed WMA was slightly diminished under construction conditions with no temperature reduction. With increased service time, the rheological characteristics of FWMA were enhanced at high temperatures, while deteriorated at low temperatures. The foaming water and service time were primary determinants of the aging as well as high and low-temperature rheological properties of FWMA without temperature construction reduction. Additionally, the aging degree of FWMA under short-term and long-term service was smaller than HMA when the construction temperature decreased. The rheological characteristics of FWMA were inferior to those of HMA during both short-term and long-term service stages. Under conditions of temperature reduction, foaming water and mixing temperature exhibited a considerable influence on the aging and rheological properties of FWMA at high and low temperatures. Therefore, the amount of water used for foaming and the temperature of production should be strictly control in the foamed warm mix asphalt technology.

Background: This study aimed to evaluate the effect of applying digital technology in orthodontic learning, students' new skills and satisfaction towards it. Methods: In total, 94 undergraduates of stomatology were recruited and randomly allocated to two groups. According to the cross-over design, both groups completed cephalometric measurements through the traditional hand-drawn method and digital technology (the Dolphin software) in different orders. By traditional hand-drawn method, students need to depict the outlines of the craniofacial anatomical structures on the sulfuric transfer paper first, then marked the measurement points and completed the measurement of line spacings and angles. By digital technology, they should mark the points in the software and adjust the automatically generated outlines of the structures and obtained the results. Besides, an online questionnaire was designed to investigate students' attitudes toward the digital technology. Two professional orthodontists were invited as instructors. They measured a lateral cranial radiograph by two methods with one week’s interval, and their intra- and inter-class correlation coefficient were measured. The means of their measurements were set as standards. Results: The inter- and intra-ICC of two instructors surpassed 90%, and there were no significant differences between their measurements, and the measurements by two methods. There were significant differences of students’ measurements (P 1-SNA

ObjectiveTo explore the clinical characteristics of testicular torsion in children with non-scrotal initial symptoms who were misdiagnosed.MethodsA retrospective analysis of 73 cases children with testicular torsion and non-scrotal symptoms who were admitted to our department from October 2013 to December 2021 was performed. Patients were divided into misdiagnosis (27 cases) and clear diagnosis at first visit (46 cases) groups. Clinical data, including age at surgery, clinical presentation, physical examination, number of visits (≥2 times), affected side, time from initial symptoms to surgery, and surgical outcomes, were collected. The TWIST (Testicular Workup for Ischemia and Suspected Torsion) score was calculated and analyzed.ResultsStatistically significant differences between the misdiagnosis and clear diagnosis groups were seen in the time from initial symptoms to surgery, the number of visits, the degree of testicular torsion, and the rate of orchiectomy (P 0.05) in age, affected side, TWIST score, guardian, direction of testicular torsion, intra-vaginal or extra-vaginal torsion, and Arda classification. Postoperative follow-up was 6–40 months. Of the 36 patients who required an orchiopexy, 1 had testicular atrophy at six months and 2 were lost to follow-up. The contralateral testis of the 37 children who underwent orchiectomies developed normally without torsion.ConclusionsThe clinical manifestations of testicular torsion in children are diverse and can easily lead to misdiagnosis. Guardians should be aware of this pathology and seek timely medical attention. When the initial diagnosis and treatment of testicular torsion is difficult, the TWIST score during the physical examination may be useful, especially for patients with intermediate-to-high risk scores. Color Doppler ultrasound can assist in making the diagnosis, but when testicular torsion is highly suspected, routine ultrasound is not necessary as it may lead to delayed surgical treatment.

Phase measuring deflectometry (PMD) stands as an extremely important technique for specular surface measurement. However, the parasitic reflection from the rear surface poses a challenge for PMD. To solve this problem, this paper proposes an effective method based on multi-frequency and phase-shifting to search for the correct phase. Firstly, the relationship between the phase error and fringe frequency is adequately investigated. Subsequently, an auxiliary function is established to find the special frequency at which the phase error is zero theoretically and the unwrapped phase is the phase of the top surface exactly. Then, the shape of the top surface can be reconstructed correctly. A standard plane element with a thickness of 40 mm and a flat glass with 19 mm were measured. The experimental results verify the feasibility of the proposed method. Considering the result of the interferometer as a reference, the RMSE of the error map is up to 20 nm for the standard plane element. The experimental results demonstrate that the proposed method can successfully untangle the superposed reflections and reliably reconstruct the top surface of the object under test.

A flame’s structural feature is a crucial parameter required to comprehensively understand the interaction between turbulence and flames. The generation and evolution processes of the structure feature have rarely been investigated in lean blowout (LBO) flame instability states. Hence, to understand the precursor features of the LBO flame, this work employed high-speed OH-PLIF measurements to acquire time-series LBO flame images and developed a novel feature extraction method based on a deep neural network to quantify the LBO features in real time. Meanwhile, we proposed a deep neural network segmentation method based on a tri-map called the Fire-MatteFormer, and conducted a statistical analysis on flame surface features, primarily holes. The statistical analysis results determined the relationship between the life cycle of holes (from generation to disappearance) and their area, perimeter, and total number. The trained Fire-MatteFormer model was found to represent a viable method for determining flame features in the detection of incipient LBO instability conditions. Overall, the model shows significant promise in ascertaining local flame structure features.

A 40 cm length Bis(triethoxysilyl)ethane (BTESE) membrane having different pore sizes was successfully prepared by changing the number of coating times for gas permeation (GP) and organic solvent reverse osmosis (OSRO) separation study. It was found that BTESE-6 membranes prepared through six-time coating consisted of small-sized pores in the range 0.56 to 0.64 nm estimated using modified Gas Translation (mGT) method and 0.59 to 0.67 nm estimated by nanopermporometry (NPP) method, respectively. These membranes demonstrated a high DMF rejection, RDMF > 95% with total flux, Jv total > 5 kg m−2 h−1 at operating condition feed pressure, Pf: 8 MPa; feed temperature, Tf : 50 °C; and feed flowrate, Qf : 30 mL/min; and they exhibited a high degree selectivity of He/SF6 in the range of ~ 260–3400 at a permeation temperature 200 °C. On the other hand, the larger pore sizes of the BTESE-4 membranes (pore size estimates > 0.76 nm to 1.02 nm) exhibited low DMF rejection and a low degree selectivity of He/SF6 around ~30% and 25, respectively, at the same operating condition as BTESE-6. Both GT and NPP methods can be considered as an indicator of the measurement membrane pore size. From this study, it was found that He and SF6 gases can be some of the potential predictors for water and DMF permeance. Furthermore, by comparing our OSRO membrane with other PV membranes for DMF/H2O separation, our BTESE-6 membranes still exhibited high flux in the range of 3–6 kg m−2 h−1 with a separation factor H2O/DMF in the range of 80–120.

Abstract Early prognosis of clinical efficacy is an urgent need for oncology drug development. Herein, we systemically examined the quantitative approach of tumor growth inhibition (TGI) and survival modeling in the space of relapsed and refractory multiple myeloma (MM), aiming to provide insights into clinical drug development. Longitudinal serum M‐protein and progression‐free survival (PFS) data from three phase III studies (N = 1367) across six treatment regimens and different patient populations were leveraged. The TGI model successfully described the longitudinal M‐protein data in patients with MM. The tumor inhibition and growth parameters were found to vary as per each study, likely due to the patient population and treatment regimen difference. Based on a parametric time‐to‐event model for PFS, M‐protein reduction at week 4 was identified as a significant prognostic factor for PFS across the three studies. Other factors, including Eastern Cooperative Oncology Group performance status, prior anti‐myeloma therapeutics, and baseline serum ß2‐microglobulin level, were correlated with PFS as well. In conclusion, patient disease characteristics (i.e., baseline tumor burden and treatment lines) were important determinants of tumor inhibition and PFS in MM patients. M‐protein change at week 4 was an early prognostic biomarker for PFS.

The building materials industry is the foundation of national economy. Intelligent reforms and digital transformations have deepened the application of new technologies and brought about more digital scenarios, which drives the development of industrial software for the building materials industry and facilitates the high-quality development of the building materials industry. Industrial software is a link that connects industrial design and manufacturing processes with informatization, intelligence, and digitization. In this study, we categorize the industrial software for the building materials industry into the following four types based on industrial characteristics, technical processes, and core functions of the software: operation management; research, development and design; production control; and service support software. Subsequently, the development status of industrial software for the building materials industry in China and abroad is reviewed, and the gap between China and the advanced international level regarding industrial software development is analyzed. The key development directions are clarified from the perspectives of improving weak links, promoting replacement, and developing advantages. The research suggests that the industrial software for the building materials industry should be developed from the following technological perspectives: (1) breaking technical barriers in key areas, (2) ensuring the safety and control of key links, (3) promoting the application of information technology innovations, and (4) building an industry public service platform. Moreover, we propose the following development strategies: (1) optimizing the support policies, (2) improving the industrial software standards system, (3) encouraging industry–university–research–application collaboration to address key problems, (4) cultivating industrial software compound talents, and (5) establishing a good software application ecology.

During the Second Tibetan Plateau Scientific Expedition and Research Program, we discovered that white terricolous lichenized fungal species of Buellia De Not. were widely distributed across the Tibetan Plateau. After examining their morphology, chemistry and phylogeny, we describe Buellia alpina Xin Y. Wang & Li S. Wang, sp. nov. as new to science. It is present in alpine meadows, and is characterized by its effigurate thallus, distinct linear marginal lobes, cover of thick white pruina and four-spored asci. This is also the first report of Buellia elegans Poelt and Buellia epigaea (Pers.) Tuck from China. The Buellia epigaea-group has previously been characterized by white and often effigurate thalli that occur mainly on soil. However, our results show that species in this group actually belong to two distinct clades. This conclusion is based on analyses of the nuITS region and the combined regions dataset (nuITS-nuLSU-mtSSU-β-tubulin). We discuss differences in morphology, anatomy, chemistry and ecology among the putative Buellia epigaea-group. Detailed descriptions and figures for the three species from China and a key for species of Buellia epigaea-group are provided.

Abstract Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials have demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan and delaying ageing in various species such as yeast, drosophila, rodent, primate and human. It emerges to develop the precision-nutrition therapeutics to slow age-related biological processes and treat diverse diseases. However, the nutritive advantages frequently diversify among individuals as well as organs and tissues, which brings challenges in this field. In this review, we summarize the different forms of dietary interventions extensively prescribed for healthspan improvement and disease treatment in pre-clinical or clinical. We discuss the nutrient-mediated mechanisms including metabolic regulators, nutritive metabolism pathways, epigenetic mechanisms and circadian clocks. Comparably, we describe diet-responsive effectors by which dietary interventions influence the endocrinic, immunological, microbial and neural states responsible for improving health and preventing multiple diseases in humans. Furthermore, we expatiate diverse patterns of dietotheroapies, including different fasting, calorie-restricted diet, ketogenic diet, high-fibre diet, plants-based diet, protein restriction diet or diet with specific reduction in amino acids or microelements, potentially affecting the health and morbid states. Altogether, we emphasize the profound nutritional therapy, and highlight the crosstalk among explored mechanisms and critical factors to develop individualized therapeutic approaches and predictors.

Abstract Background Regulatory T cells (Treg cells) in the peripheral blood of patients with pulmonary tuberculosis (PTB) may be closely related to the progression of PTB. In this study, the distribution characteristics and clinical importance of CD8+CD28− Treg cells in patients with tuberculosis were systematically analyzed, and the role and importance of CD8+CD28− Treg cells in influencing the immune response and progression of tuberculosis were discussed, which will provide immunological indices and reference values for the clinical diagnosis of tuberculosis. Methods Flow cytometry, sputum smears and computed tomography imaging were used to analyze the distribution characteristics of CD8+CD28− Treg cells in the peripheral blood of patients with PTB and the correlation between CD8+CD28−Treg cells and clinical and immune indices. Results The percentages of CD4+CD25high and CD8+CD28− Treg cells in the peripheral blood of patients with PTB were significantly higher than those in the healthy control (HC) group. Further analysis showed that the percentage of CD4+CD25highTreg cells in the Stage II group was significantly higher than that in the HC group. The percentages of CD4+CD25high and CD8+CD28− Treg cells increased significantly in patients in the Stage II group. The proportion of CD8+CD28− Treg cells was directly proportional to the degree of positivity in sputum smears, while CD4+CD25highTreg cells did not exhibit this trend. The correlations between the percentage of CD4+CD25high and CD8+CD28− Treg cells and the percentage of lymphocyte subsets were examined. The percentage of CD8+CD28− Treg cells was negatively correlated with the percentage of CD4+T cells and positively correlated with the CD8+T cell percentage in the HC and PTB groups. The percentage of CD4 + CD25highTreg cells was positively correlated with the percentage of CD4+T cells only in the PTB group. Conclusions This study was the first to show that the proportion of CD8+CD28− Treg cells in the peripheral blood of patients with PTB was significantly increased, and the increase in CD8+CD28− Treg cells was related to the progression of PTB, which may affect the proportion of immune cell subsets by inhibiting the immune response, resulting in the progression of PTB.

Objective To analyze the risk factors of postoperative complications after craniofacial flap repair, and to establish a risk prediction model. Methods A total of 120 patients who underwent skin flap repair from October 2017 to September 2020 were selected. Univariate and logistic multivariate regression analyses were used to screen the risk factors for complications after skin flap repair, and a personalized predictive nomogram model was established. Results The incidence of postoperative complications was 25.83%. The main complications were flap vascular crisis, infection, flap avulsion, subcutaneous hematoma and edema. Logistic multivariate regression analysis revealed that the risk factors for complications after skin flap repair included venous end-to-side anastomosis (OR=3.766, 95% CI: 1.587~8.938), excessive intraoperative blood loss (OR=2.889, 95% CI: 1.089~7.668), smoking history (OR=4.697), 95% CI: 1.558~14.161), physician′s surgical skill (OR=3.062, 95% CI: 1.183~7.922) and improper flap design (OR=2.399, 95% CI: 0.861~6.686) (P

IntroductionUsing black soldier fly larvae (BSFLs) to treat food waste is one of the most promising environmental protection technologies.MethodsWe used high-throughput sequencing to study the effects of different nutritional compositions on the intestinal microbiota and digestive enzymes of BSF.ResultsCompared with standard feed (CK), high-protein feed (CAS), high-fat feed (OIL) and high-starch feed (STA) had different effects on the BSF intestinal microbiota. CAS significantly reduced the bacterial and fungal diversity in the BSF intestinal tract. At the genus level, CAS, OIL and STA decreased the Enterococcus abundance compared with CK, CAS increased the Lysinibacillus abundance, and OIL increased the Klebsiella, Acinetobacter and Bacillus abundances. Diutina, Issatchenkia and Candida were the dominant fungal genera in the BSFL gut. The relative abundance of Diutina in the CAS group was the highest, and that of Issatchenkia and Candida in the OIL group increased, while STA decreased the abundance of Diutina and increased that of Issatchenkia. The digestive enzyme activities differed among the four groups. The α-amylase, pepsin and lipase activities in the CK group were the highest, and those in the CAS group were the lowest or the second lowest. Correlation analysis of environmental factors showed a significant correlation between the intestinal microbiota composition and digestive enzyme activity, especially α-amylase activity, which was highly correlated with bacteria and fungi with high relative abundances. Moreover, the mortality rate of the CAS group was the highest, and that of the OIL group was the lowest.DiscussionIn summary, different nutritional compositions significantly affected the community structure of bacteria and fungi in the BSFL intestinal tract, affected digestive enzyme activity, and ultimately affected larval mortality. The high oil diet gave the best results in terms of growth, survival and intestinal microbiota diversity, although the digestive enzymes activities were not the highest.

Thin-film nanocomposite (TFN) membranes are promising in improving water treatment due to their high permeability and selectivity. However, little is known about the mechanism by which nanoparticles enhance their performance. In this study, we prepared two series of TFN membranes containing ∼40 nm-sized zeolitic imidazolate framework (ZIF-8) nanoparticles, one with a hydrophobic porous form and the other with a nonporous amorphous form (aZIF-8). The TFN membranes containing 0.15 w/v% ZIF-8 exhibited a 100% increase in water permeance while maintaining a similar NaCl rejection (98.38%) compared to thin-film composite (TFC) membranes used in brackish water reverse osmosis (BWRO). In contrast, adding the same amount of aZIF-8 resulted in almost no water permeance enhancement. By comparing the physicochemical properties of the two materials and the two series of membranes, we found that the only difference was the presence or absence of internal hydrophobic pore structures. We proposed that the hydrophobic internal pores of nanoparticles served as extra water channels while preventing the passage of NaCl during BWRO.

BackgroundPercutaneous vertebroplasty (PVP) is a common treatment for osteoporotic vertebral compression fracture (OVCF). Perioperative bleeding is usually rare, so there are few reports of shock. However, we developed shock after treating a case of OVCF of the 5th thoracic vertebra with PVP.Case presentationAn 80 years old female patient received PVP due to OVCF of the 5th thoracic vertebra. The operation was successfully completed and the patient returned to the ward safely after the operation. At 90 min after operation, she developed shock, which was induced by subcutaneous hemorrhage up to 1500 ml at the puncture site. Before using vascular embolization, transfusion and blood transfusion were used to maintain blood pressure, and local ice bag compression was used to reduce swelling and stop bleeding, which achieved successful hemostasis. She recovered and discharged after 15 days, with the hematoma having absorbed. There was no recurrence during the 17-month follow-up.ConclusionAlthough PVP is considered to be a safe and effective method to treat OVCF, the possible hemorrhagic shock still needs to arouse the vigilance of surgeons.

ObjectiveMotor recovery is crucial in stroke rehabilitation, and acupuncture can influence recovery. Neuroimaging and machine learning approaches provide new research directions to explore the brain functional reorganization and acupuncture mechanisms after stroke. We applied machine learning to predict the classification of the minimal clinically important differences (MCID) for motor improvement and identify the neuroimaging features, in order to explore brain functional reorganization and acupuncture mechanisms for motor recovery after stroke.MethodsIn this study, 49 patients with unilateral motor pathway injury (basal ganglia and/or corona radiata) after ischemic stroke were included and evaluated the motor function by Fugl–Meyer Assessment scores (FMA) at baseline and at 2-week follow-up sessions. Patients were divided by the difference between the twice FMA scores into one group showing minimal clinically important difference (MCID group, n = 28) and the other group with no minimal clinically important difference (N-MCID, n = 21). Machine learning was performed by PRoNTo software to predict the classification of the patients and identify the feature brain regions of interest (ROIs). In addition, a matched group of healthy controls (HC, n = 26) was enrolled. Patients and HC underwent magnetic resonance imaging examination in the resting state and in the acupuncture state (acupuncture at the Yanglingquan point on one side) to compare the differences in brain functional connectivity (FC) and acupuncture effects.ResultsThrough machine learning, we obtained a balance accuracy rate of 75.51% and eight feature ROIs. Compared to HC, we found that the stroke patients with lower FC between these feature ROIs with other brain regions, while patients in the MCID group exhibited a wider range of lower FC. When acupuncture was applied to Yanglingquan (GB 34), the abnormal FC of patients was decreased, with different targets of effects in different groups.ConclusionFeature ROIs identified by machine learning can predict the classification of stroke patients with different motor improvements, and the FC between these ROIs with other brain regions is decreased. Acupuncture can modulate the bilateral cerebral hemispheres to restore abnormal FC via different targets, thereby promoting motor recovery after stroke.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=37359, ChiCTR1900022220.

AimAppraise the clinical features and influencing factors of the hospitalization times and length of stay in bipolar disorder (BD) patients.MethodsThis is a multicenter, observational, cohort study of patients diagnosed of type I or type II bipolar disorder. Five hundred twenty outpatients in seven hospitals from six cities in China were recruited from February 2013 to June 2014 and followed up using a continuous sampling pattern. The research included a retrospective period of 12 months and the prospective period of 9 months. The demographic and clinical features of the patients were collected. The influencing factors that could affect the length of stay (number of days spent in the hospital in the prospective period) were analyzed by poisson's regression and the hospitalization times (times of hospitalization in the prospective and retrospective period) was analyzed by general linear model. The selected variables included gender, age, years of education, occupational status, residence status, family history of mental disease, comorbid substance abuse, comorbid anxiety disorder, times of suicide (total suicide times that occurred in the retrospective and prospective period), polarity of the first mood episode, and BD type(I/II).ResultsPoisson's regression analysis showed that suicide times [Incidence Rate Ratio (IRR) = 1.20, p < 0.001], use of antipsychotic (IRR = 0.62, p = 0.011), and use of antidepressant (IRR = 0.56, p < 0.001) were correlated to more hospitalization times. Linear regression analysis showed that BD type II (β = 0.28, p = 0.005) and unemployment (β = 0.16, p = 0.039) which might mean longer duration of depression and poor function were correlated to longer length of stay. However, patients who experienced more suicide times (β = −0.21, p = 0.007) tended to have a shorter length of stay.ConclusionOverall, better management of the depressive episode and functional rehabilitation may help to reduce the length of stay. BD patients with more hospitalization times were characterized by higher risk of suicide and complex polypharmacy. Patients at high risk of suicide tended to have inadequate therapy and poor compliance, which should be assessed and treated adequately during hospitalization.Clinical trial registrationwww.ClinicalTrials.gov, Identifier: NCT01770704.

Abstract High‐performance flexible strain sensors are gaining more and more attention with their bespoken detection range, excellent sensing performance, and good stability, which are highly desired in wearable electronics. Herein, a thermoplastic polyurethane elastomer (TPU) fibrous membrane is prepared as a flexible substrate by electrostatic spinning technology, then a coating of polydopamine is formed through fast synthesizing the dopamine on TPU fibrous membrane surface and loaded with carbon nanotubes (CNTs) to develop an extremely sensitive flexible strain sensor. The flexible sensor prepared by TPU fibrous membrane coated with polydopamine layer has an outstanding sensibility under the pulling force (Gauge Factor of 10 528.53 with 200% strain), rapid reaction time (188–221 ms), wide sensing range (up to 200%), good stability, and durability. The theoretical studies reveal the underlying cause for the high sensitivity and the inherent relationship between the amount of conducting routes and the length between adjacent conducting fillers in the sensor. The demonstration of the device shows a promising application to sense human motion at various locations of the body, with the accurate and stable electrical signal output generated at corresponding motion.

ObjectiveThe Chinese version of 15-item negative symptom assessment (NSA-15) is an instrument with a three-factor structure specifically validated for assessing negative symptoms of schizophrenia. To provide a reference for future practical applications in the recognition of schizophrenia patients with negative symptoms, this study aimed to determine an appropriate NSA-15 cutoff score regarding negative symptoms to identify prominent negative symptoms (PNS).MethodsA total of 199 participants with schizophrenia were recruited and divided into the PNS group (n = 79) and non-PNS group (n = 120) according to scale for assessment of negative symptoms (SANS) scores. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal NSA-15 cutoff score for identifying PNS.ResultsThe optimal cutoff NSA-15 score for identifying PNS was 40. Communication, emotion and motivation factors in the NSA-15 had cutoffs of 13, 6, and 16, respectively. The communication factor score had slightly better discrimination than scores on the other two factors. The discriminant ability of the global rating of the NSA-15 was not as good as that of the NSA-15 total score (area under the curve (AUC): 0.873 vs. 0.944).ConclusionThe optimal NSA-15 cutoff scores for identifying PNS in schizophrenia were determined in this study. The NSA-15 provides a convenient and easy-to-use assessment for identifying patients with PNS in Chinese clinical situations. The communication factor of the NSA-15 also has excellent discrimination.

Neurodegenerative diseases (NDs) are chronic conditions that result in progressive damage to the nervous system, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic lateral sclerosis (ALS). Age is a major risk factor for NDs. Telomere shortening is a biological marker of cellular aging, and telomerase reverse transcriptase (TERT) has been shown to slow down this process by maintaining telomere length. The blood-brain barrier (BBB) makes the brain a unique immune organ, and while the number of T cells present in the central nervous system is limited, they play an important role in NDs. Research suggests that NDs can be influenced by modulating peripheral T cell immune responses, and that TERT may play a significant role in T cell senescence and NDs. This review focuses on the current state of research on TERT in NDs and explores the potential connections between TERT, T cells, and NDs. Further studies on aging and telomeres may provide valuable insights for developing therapeutic strategies for age-related diseases.

IntroductionDiabetic sarcopenia (DS) is characterized by muscle atrophy, slower nerve conduction, reduced maximum tension generated by skeletal muscle contraction, and slower contraction rate. Hence, DS can cause limb movement degeneration, slow movement, reduced balance, reduced metabolic rate, falls, fractures, etc. Moreover, the relevant early biological metabolites and their pathophysiological mechanism have yet to be characterized.MethodThe current cross-sectional study employed serum metabolomics analysis to screen potential noninvasive biomarkers in patients with diabetic sarcopenia. A total of 280 diabetic patients were enrolled in the study (n = 39 sarcopenia [DS], n = 241 without sarcopenia [DM]). Ten patients were randomly selected from both groups. Non-targeted metabolomic analysis was performed by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.ResultsA total of 632 differential metabolites were identified, including 82 that were significantly differentially abundant (P < 0.05, VIP > 1, FC > 1.2 or FC < 0.8). Compared with the DM group, the contents of pentadecanoic acid, 5'-methylthioadenosine (5'-MTA), N,N-dimethylarginine (asymmetric dimethylarginine, ADMA), and glutamine in the DS group were significantly increased, while that of isoxanthohumol was decreased.DiscussionBased on receiver operating characteristic curve analysis, pentadecanoic acid, 5'-MTA, ADMA, and glutamine may serve as potential biomarkers of DS. Moreover, ATP-binding cassette (ABC) transporters and the mammalian target of the rapamycin signaling pathway were found to potentially have important regulatory roles in the occurrence and development of DS (P < 0.05). Collectively, the differential metabolites identified in this study provide new insights into the underlying pathophysiology of DS and serve as a basis for therapeutic interventions.

BackgroundAs the major microtubule organizing center in animal cells, the centrosome is implicated with human breast tumor in multiple ways, such as promotion of tumor cell immune evasion. Here, we aimed to detect the expression of centrosome-related genes (CRGs) in normal and malignant breast tissues, and construct a novel centrosome-related prognostic model to discover new biomarkers and screen drugs for breast cancer.MethodsWe collected CRGs from the public databases and literature. The differentially expressed CRGs between normal and malignant breast tissues were identified by the DESeq2. Univariate Cox and LASSO regression analyses were conducted to screen candidate prognostic CRGs and develop a centrosome-related signature (CRS) to score breast cancer patients. We further manipulated and visualized data from TCGA, GEO, IMvigor210, TCIA and TIMER to explore the correlation between CRS and patient outcomes, clinical manifestations, mutational landscapes, tumor immune microenvironments, and responses to diverse therapies. Single cell analyses were performed to investigate the difference of immune cell landscape between high- and low-risk group patients. In addition, we constructed a nomogram to guide clinicians in precise treatment.ResultsA total of 726 CRGs were collected from the public databases and literature. PSME2, MAPK10, EIF4EBP1 were screened as the prognostic genes in breast cancer. Next, we constructed a centrosome-related prognostic signature and validated its efficacy based on the genes for predicting the survival of breast cancer patients. The high-risk group patients had poor prognoses, the area under the ROC curve for 1-, 3-, and 5-year overall survival (OS) was 0.77, 0.67, and 0.65, respectively. The predictive capacity of CRS was validated by other datasets from GEO dataset. In addition, high-risk group patients exhibited elevated level of mutational landscapes and decreased level of immune infiltration, especially T and B lymphocytes. In terms of treatment responses, patients in the high-risk group were found to be resistant to immunotherapy but sensitive to chemotherapy. Moreover, we screened a series of candidate anticancer drugs with high sensitivity in the high-risk group.ConclusionOur work exploited a centrosome-related prognostic signature and developed a predictive nomogram capable of accurately predicting breast cancer OS. The above discoveries provide deeper insights into the vital roles of the centrosome and contribute to the development of personalized treatment for breast cancer.

IntroductionThe revised Hopkins Verbal Learning Test-Revised (HVLT-R) and the Brief Visual-Spatial Memory Test-Revised (BVMT-R) are two widely used test involving verbal and visual learning and memory. In the two tests, six different versions are assembled, respectively, to prevent learning effects. Currently, no researchers have compared the six versions of the two tests. Thus, their usefulness in clinical studies requiring multiple follow-ups is limited. In this work, we confirm the equivalence of six HVLT-R and BVMT-R versions.Methods20 people completed all six HVLT-R and BVMT-R versions, while 120 people were randomly assigned to complete one of the six versions of each test. The Intelligence Quotient (IQ) level is measured using the short version of the Wechsler Adult Intelligence test. R4.2.0 is used for statistical analysis. The K-Related sample test (a non-parametric test) is used to observe the differences in test scores among the 20 subjects. The one-way Analysis of Variance (ANOVA) test is utilized to analyze the differences in test scores among the 120 subjects. The scores on different versions are compared using two similar sample tests. The HVLT-R Total Learning, the HVLT-R Delayed Recall, the BVMT-R Total Learning, and the BVMT-R Delayed Recall are indexes for comparison. Version and test scores are used as research factors, while different versions are used as research levels.ResultsThe results suggest that HVLT-R and BVMT-R versions 3, 5 and 6 are equally difficult, and relatively easy compared to versions 1, 2 and 4. HVLT-R versions 3, 5, and 6 show good reliability and can be used interchangeably when testing word learning ability or short-term memory; BVMT-R Versions 3, 5, and 6 show acceptable reliability and can be can be used interchangeably.DiscussionIn the study of multiple follow-ups, it is a must to avoid discrepant versions and choose other equivalent versions. The results from this study could be used as a guide for upcoming studies and clinical applications in China.

BackgroundGlioblastoma multiforme (GBM) is the most lethal brain cancer in adults, characterized by rapid growth, extensive invasiveness, and poor prognosis, and there is still a lack of effective treatments. Here, we aimed to explore the role of triptolide (TPL), purified from Tripterygium wilfordii Hook F, on glioblastoma cell growth, apoptosis, proliferation, migration and invasion, as well as potential underlying mechanisms.MethodsThe publicly available clinical data of Brain Lower Grade Glioma (LGG) from The Cancer Genome Atlas (TCGA) had been screened to observe PROX1 expression. The Kaplan-Meier analysis was used to analyze the relationship between PROX1 expression and GBM prognosis. CCK8, cell cycle, EDU, apoptosis, wound healing, and transwell assays were performed to detect the effects of TPL on glioblastoma U251 cell viability, cell cycle, proliferation, apoptosis, migration and invasion, respectively. Further, a soft agar colony assay was used to calculate the growth of glioblastoma cells. The qRT-PCR and western blot were conducted to quantify PROX1 mRNA and protein levels. The transcriptional regulation of TPL was detected by Dual luciferase reporter assay.ResultsWe found that TPL inhibited glioblastoma cell viability, proliferation, cell cycle, migration and invasion, but enhanced apoptosis in a dose-dependent manner. The expression of cell cycle inhibitor, P21, and pro-apoptosis factor, Bax was increased, while invasion-related factors MMP2 and MMP9 were silenced after TPL treatments. Mechanistically, TPL showed transcriptional inhibition of PROX1 appearance. Moreover, ectopic expression of PROX1 partially rescued the effects of TPL on glioblastoma cell viability, proliferation, apoptosis, migration and invasion, and on the expression of cell function-related genes.ConclusionThis study verified that TPL inhibited the progression of glioblastoma cells by transcriptionally depressing the expression of PROX1.

Neuropathic pain (NP) induced by spinal cord injury (SCI) often causes long-term disturbance for patients, but the mechanisms behind remains unclear. Here, our study showed SCI-induced ectopic expression of Nav1.7 in abundant neurons located in deep and superficial laminae layers of the spinal dorsal horn (SDH) and upregulation of Nav1.7 expression in dorsal root ganglion (DRG) neurons in mice. Pharmacologic studies demonstrated that the efficacy of the blood–brain-barrier (BBB) permeable Nav1.7 inhibitor GNE-0439 for attenuation of NP in SCI mice was significantly better than that of the BBB non-permeable Nav1.7 inhibitor PF-05089771. Moreover, more than 20% of Nav1.7-expressing SDH neurons in SCI mice were activated to express FOS when there were no external stimuli, suggesting that the ectopic expression of Nav1.7 made SDH neurons hypersensitive and Nav1.7-expressing SDH neurons participated in central sensitization and in spontaneous pain and/or walking-evoked mechanical pain. Further investigation showed that NGF, a strong activator of Nav1.7 expression, and its downstream JUN were upregulated after SCI in SDH neurons with similar distribution patterns and in DRG neurons too. In conclusion, our findings showed that the upregulation of Nav1.7 was induced by SCI in both SDH and DRG neurons through increased expression of NGF/JUN, and the inhibition of Nav1.7 in both peripheral and spinal neurons alleviated mechanical pain in SCI mice. These data suggest that BBB permeable Nav1.7 blockers might relieve NP in patients with SCI and that blocking the upregulation of Nav1.7 in the early stage of SCI via selective inhibition of the downstream signaling pathways of NGF or Nav1.7-targeted RNA drugs could be a strategy for therapy of SCI-induced NP.

Abstract Pancreatic cancer (PC) is one of the deadliest malignant tumors, and its resistance to gemcitabine chemotherapy is the primary reason for poor prognosis in patients. Ubiquitin-like protein FAT10 has recently been reported to promote tumor chemotherapy resistance. In this study, the expression of FAT10 in PC was significantly higher than that in adjacent noncancerous tissues. Increased expression of FAT10 in PC was related to a late TNM stage and decreased overall survival. Functional experiments revealed that downregulating the expression of FAT10 inhibits the proliferation and epithelial-mesenchymal transition (EMT) of PC cells, promotes the apoptosis of PC cells, and enhances sensitivity to gemcitabine chemotherapy. In addition, upregulation of FAT10 increased the expression of FOXM1 protein. The effect of downregulating FAT10 was reversed by FOXM1 overexpression, and FOXM1 knockdown inhibited EMT driven by FAT10 overexpression. Mechanistically, FAT10 stabilized the expression of FOXM1 by competing with ubiquitin to bind FOXM1 and inhibiting the ubiquitination-mediated degradation of FOXM1. In conclusion, the FAT10-FOXM1 axis is a pivotal driver of PC proliferation and gemcitabine resistance, and the results provide novel insights into chemotherapy resistance in PC.

Magnetism has revolutionized important technologies, and continues to bring forth new phenomena in emergent materials and reduced dimensions. Here, using first-principles calculations, we demonstrate that the already-synthesized two-dimensional (2D) Ni-tetracyanoquinodimethane (Ni2(TCNQ)2) lattice is a stable ferromagnetism material with multiple spin-polarized Dirac cones. The conical bands in proximity of the Fermi level can be tuned by external tensile strain and show the fourfold degenerate electronic states at the critical tensile strain of ∼2.35 %, whose energy dispersion is consistent with 2D Cairo pentagonal lattice. In addition, spin-orbital coupling can open a band gap at the Dirac point of A, leading to topologically nontrivial electronic states characterized by the non-zero Chern number and the edge states of nanoribbon. Our results offer versatile platforms for the realization of massless spintronics with full-spin polarization in 2D Cairo pentagonal Ni2(TCNQ)2 Lattice.

Abstract Background It was generally accepted that obesity could increase the morbidity and mortality of surgical patients. However, the influence of body mass index (BMI) on short-term and long-term surgical outcomes of laparoscopic hepatectomy (LH) for patients with liver carcinoma remains unclear. The aim of this study was to evaluate the influence of BMI on surgical outcomes. Methods From August 2003 to April 2016, 201 patients with liver carcinoma who underwent LH were enrolled in our study. Based on their BMI in line with the WHO’s definition of obesity for the Asia-Pacific region, patients were divided into three groups: underweight (BMI< 18.5 kg/m2), normal weight (18.5≤BMI< 23 kg/m2), and overweight (BMI≥ 23 kg/m2). Demographics and surgical outcomes of laparoscopic hepatectomy were compared in different BMI stratification. We investigated overall survival and relapse-free survival across the BMI categories. Results Of the 201 patients, 23 (11.44%) were underweight, 96 (47.76%) were normal weight, and 82 (40.80%) were overweight. The overall complication rate in the underweight group was much higher than that in the normal weight and overweight groups (p=0.048). Postoperative complications, underweight patients developed grade III or higher Clavien-Dindo classifications (p=0.042). Among the three BMI groups, there were no significant differences in overall and relapse-free survival with Kaplan-Meier analysis (p=0.104 and p=0.190, respectively). On the other hand, gender, age, liver cirrhosis, bile leak, ascites, and Clavien classification (III-IV) were not independent risk factors for overall and relapse-free survival in multivariable Cox proportional hazards models. Conclusions BMI status does not affect patients with liver carcinoma long-term surgical outcomes concerned to overall survival and relapse-free survival after laparoscopic hepatectomy. However, being underweight was associated with an increased perioperative complication rate, and perioperative careful monitoring might be required after hepatectomy for underweight with liver carcinoma.

The work deals with the synthesis of metakaolin phosphate-based geopolymers (MKPGs) using calcined kaolin, phosphoric acid (PA), and mixing water. The metakaolin was thermally treated at 750 °C for different holding times. The different duration in the heating at 750 °C led to the gradual dehydroxylation of kaolin to metakaolin with a different structural water content (inter-layer and inner-layer residual water). Considering the temperature or duration of the thermal dehydroxylation, the inter-layer water evolved first, followed by the inner-layer water at a higher temperature or later time. The polymerisation degree is closely linked with the presence of the inter- or inner-layer water. It was found that the inter-layer residual water negatively influences the compressive strength, while the water in the inner-layer exerts a more negligible effect on the resistance. Indeed, the inter-layer water loss is linked to the structural changes in kaolinite; but the loss of water from the inner-layer is related to the structural changes in the metakaolinite. The holding time of dehydroxylation and water-to-metakaolin (W/M) ratio were optimised. A maximum strength of 57.6 MPa was achieved at the Al/P and W/M ratios of 1.0 and 0.40, respectively. The mass losses at the different temperatures showed that the additional excess mixing water increased the porosity of the MKPGs, resulting in a decrease in the compressive strength.

Abstract Human activities such as urbanization often has negative affects wildlife. However, urbanization can also be beneficial to some animals by providing suitable microhabitats. To test the impact of urbanization on cold-blooded animals, we first conducted a snake survey at a national nature reserve (Xianghai natural reserve) and an adjacent tourist bird park (Red-crowned Crane Park). We show high presence of Elaphe dione in the tourist park even with high human activities and predator population (the endangered, red-crowned crane, Grus japonensis). We then radio-tracked 20 individuals of E. dione, set seven camera traps, and recorded the temperature of the snakes and artificial structures in Crane Park to document their space use, activity, and thermal preference, respectively. Our results show E. dione preferred to use artificial facilities to shelter from their predators and for thermoregulation. The high number of rats from the camera traps indicate abundant prey items. Overall, E. dione appears to be adapted to modified habitats and may expand population size at the current study site.

Swarm behavior can often produce value and complexity far beyond individual behavior.In order to more effectively derive swarm intelligence on the basis of individual intelligence, it is necessary to scientifically measure the level of swarm intelligence based on swarm entropy, and use swarm entropy as the guiding goal to promote the enhancement and evolution of swarm intelligence.Aiming at this important scientific problem, the unmanned car group as the research object was taken and a multi-agent soft Q learning method based on parameter sharing and group strategy entropy was proposed.Which by sharing the observation information of the agent, combined with the maximum entropy reinforcement learning method, to achieve continuous learning and updating of swarm strategies in exploratory tasks.At the same time, by defining swarm entropy as a measurement tool, characterizing the entropy change pattern in swarm learning, realizing the quantitative analysis of the gathering process of swarm intelligence.

Abstract Compound Kushen injection (CKI) is the most widely used traditional Chinese medicine preparation for the comprehensive treatment of colorectal cancer (CRC) in China, but its underlying molecular mechanisms of action are still unclear. The present study employed a network pharmacology approach, in which we constructed a “bioactive compound-target-pathway” network. Experimental RNA sequencing (RNA-Seq) analysis was performed to identify a key “bioactive compound-target-pathway” network for subsequent experimental validation. Cell cycle, proliferation, autophagy, and apoptosis assays and a model of azoxymethane/dextran sodium sulfate-induced colorectal carcinogenesis in mice were employed to detect the biological effect of CKI on CRC. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry were performed to verify the selected targets and pathways. We constructed a predicted network that included 82 bioactive compounds, 34 targets, and 33 pathways and further screened an anti-CRC CKI “biological compound (hesperetin 7-O-rutinoside, genistein 7-O-rutinoside, and trifolirhizin)-target (p53 and checkpoint kinase 1 [CHEK1])” network that targeted the “cell cycle pathway”. Validation experiments showed that CKI effectively induced the cell-cycle arrest of CRC cells in vitro and suppressed the development of CRC in vivo by downregulating the expression of p53 and CHEK1. Our findings confirmed that inducing cell-cycle arrest by CKI is an important mechanism of its anti-CRC action, which provides a direct and scientific experimental basis for the clinical application of CKI.

Our previous study showed that early supplementation with 10 g/(d·head) of galacto-oligosaccharides (GOS) in newborn Holstein dairy calves reduced the incidence of diarrhea and improved growth performance and mineral absorption. Since the dose of 10 g/(d·head) was the lowest by dose screening in our previous study, the present study was designed to investigate whether a lower amount of GOS has similar effects on growth performance, immune function, serum nutrients in newborn Holstein heifer calves, and to further investigate its effect on appetite-related hormones. Twenty-eight healthy newborn (1 day of age) Holstein heifers with similar average body weight (41.18 ± 1.90 kg) were randomly divided into four groups (n = 7): the control group (CON group), which received heated raw milk, and three experimental groups, which received heated raw milk supplemented with 2.5 (GOS2.5 group), 5 (GOS5 group), and 10 g/(d·head) (GOS10 group) GOS. All heifer calves were fed the same starter for 28 d. Supplementation with GOS linearly increased the final body weight, average daily gain, and feed efficiency in heifer calves (p < 0.01). Compared with the control group, the average daily gain and feed efficiency of heifer calves were significantly higher in the GOS5 and GOS10 groups than in the control group (p < 0.05). Furthermore, supplementation with GOS quadratically enhanced the starter and total average daily feed intake of the heifers (p < 0.01), especially in the GOS2.5 and GOS5 groups, (p < 0.05 vs. CON). The serum concentration of immunoglobulin A was linearly increased by GOS supplementation (p < 0.05), and the levels in the GOS5 and GOS10 groups were significantly higher than those in the CON group. Meanwhile, GOS linearly decreased serum interleukin-1β and interleukin-6 concentrations (p < 0.05). The serum concentration of triglycerides was also linearly decreased (p < 0.05), whereas total protein and blood urea nitrogen were linearly increased (p < 0.05). Supplementation with GOS linearly decreased the serum concentration of leptin (p < 0.05) but increased cholecystokinin and glucagon-like peptide-1 (p < 0.05). Increasing doses of GOS linearly improved serum calcium and copper concentrations (p < 0.01) and quadratically enhanced the concentration of magnesium, which peaked in the GOS5 group (p < 0.05). In conclusion, GOS supplementation reduced the incidence of diarrhea and improved the growth performance and immune function of Holstein heifer calves.

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial protein involved in the metabolism of low‐density lipoprotein cholesterol. However, the role of plasma PCSK9 in predicting the efficacy of ICIs in advanced non‐small cell lung cancer (NSCLC) remains to be clarified. Methods We retrospectively reviewed the medical records of NSCLC patients who presented at Shanghai Pulmonary Hospital between April 2019 and June 2020. ELISA was conducted to detect the concentration of PCSK9. Clinical efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results A total of 55 patients were enrolled in the study. The median progression‐free survival (PFS) following treatment with ICIs in all patients was 9.9 months. The optimal threshold of baseline plasma PCSK9 was 232.2 ng/ml. Patients with low baseline plasma PCSK9 had a longer PFS (NR vs. 7.37 months, p = 0.017, HR = 0.207, 95% CI: 0.086–0.498) and a better response (ORR 71.4% vs. 43.9%, p = 0.075, DCR 100% vs. 80.5%, p = 0.098) to ICIs. Younger patients (≤66 years) with a lower PCSK9 had a significantly longer PFS and higher treatment response than those with a high baseline level of PCSK9 (NR vs. 5.83 months, p = 0.021, HR = 0.134, 95% CI: 0.044–0.409; ORR 66.7% vs. 30.0%, p = 0.106, DCR 100% vs. 75%, p = 0.153). The situation was similar in patients who received first‐line therapy (NR vs. 8.97 months, p = 0.022, HR = 0.138, 95% CI: 0.047–0.400; ORR 63.6% vs. 46.4%, p = 0.480, DCR 100% vs. 89.3%, p = 0.545). Multivariate analysis showed that low PCSK9 concentration was independently associated with PFS (p = 0.032, HR = 0.201). Conclusions Low baseline plasma PCSK9 level may predict good outcomes in patients with advanced NSCLC treated with ICIs.

Adaptive optics (AO) can effectively improve the beam quality of solid-state slab lasers. However, the aperture of the output beam increases as the output power of the laser increases, resulting in a larger measurement system. Ultimately, a more complex AO system needs to be designed. To meet the requirements of conjugate imaging in an AO system, it is of research significance to coordinate and optimize the system's structural dimensional parameters while enabling the detection of multiple parameters, such as the wave-front and beam quality. In this paper, a multiparameter measurement technique in a large-aperture rectangular laser beam aberration-correction system is proposed. The system layout is optimized with total dimensions of 400 mm × 150 mm × 246 mm (L × W × H). The AO system conforms to the requirements for conjugate detection and can perform wave-front detection, far-field evaluation, and near-field detection of a 160 mm × 120 mm rectangular beam produced from a solid-state slab laser. The findings reveal that the measured PV values of wave-fronts of the measurement system are less than 0.288 μm, the RMS is no more than 0.079 μm, the average far-field beam quality factor is 1.248 times the diffraction limit, and the average near-field beam uniformity is 0.533 at a temperature of 20 °C ± 10 °C; these results satisfy the technical parameters.

A laser time-frequency analysis ranging method based on wavelet transform for underwater target detection has been proposed in this paper. The band-pass filtering characteristics of the wavelet transform are combined with the energy conservation of the signal time-frequency domain during the wavelet time-frequency decomposition process of the echo signal. Binary spline interpolation is used to obtain the time-frequency correspondence matrix of the echo signal energy. In this method, the frequency range of the target echo signal is selected through the multi-layer wavelet time-domain decomposition process. The time-frequency energy matrix of the echo signal is extracted in the frequency range, and these frequencies are integrated to determine the restored time-domain echo signal. The corresponding delay of the target is determined by the peak detection method, and the target distance information is retrieved. The emission source is a 532 nm pulsed laser with a repetition frequency of 50 kHz, a pulse width of 1 ns, and average power of 3 W. The APD detector and the acquisition system with a bandwidth of 1 G are used to receive the echo signal. By detecting diffuse reflection targets in the water with an attenuation length of 10, the signal processing method can reduce the ranging error from 11.83 cm to less than 4 cm.

Abstract Background Current research on perinatal depression rarely pays attention to the continuity and volatility of depression symptoms over time, which is very important for the early prediction and prognostic evaluation of perinatal depression. This study investigated the trajectories of perinatal depression symptoms and aimed to explore the factors related to these trajectories. Methods The study recruited 550 women during late pregnancy (32 ± 4 weeks of gestation) and followed them up 1 and 6 weeks postpartum. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS). Latent growth mixture modelling (LGMM) was used to identify trajectories of depressive symptoms during pregnancy. Results Two trajectories of perinatal depressive symptoms were identified: “decreasing” (n = 524, 95.3%) and “increasing” (n = 26, 4.7%). History of smoking, alcohol use and gestational hypertension increased the chance of belonging to the increasing trajectories, and a high level of social support was a protective factor for maintaining a decreasing trajectory. Conclusions This study identified two trajectories of perinatal depression and the factors associated with each trajectory. Paying attention to these factors and providing necessary psychological support services during pregnancy would effectively reduce the incidence of perinatal depression and improve patient prognosis.

Accurate measurement of the spatial angle is key for plane flatness and guide rail straightness detection. This paper presents a lens-array-based optical system and an analytical model for micro-spatial angle measurements. In this system, a collimated light beam passes through four-array lenses arranged in a pyramid shape and forms regular array spots on a charge-coupled device sensor. The angles with respect to the $X$ and $Y$ axes are calculated by analyzing the distance of these spots on the CCD, the distance between adjacent apertures on the lens array, and the inclination angle between the lens array and the CCD. Using the coordinate value of the array spots on the CCD, the angle around the Z-axis can also be calculated simultaneously. Finally, the accuracy of the proposed method was verified by comparing the measured results with those of the autocollimator, and it was shown that the proposed approach enabled the achievement of RMS $\le 0.1''$ . Additionally, this measurement system which is consists of a laser source, lens arrays and CCD, compared with other methods, is smaller in volume and more convenient to carry.

Temperature compensation occupies a significant function in the insulation condition evaluation of converter transformer bushings based on the Frequency Domain Spectroscopy (FDS), which could influence the accuracy of its insulation diagnosis. In order to accurately obtain the variation law of FDS at different temperature, a Resin Impregnated Paper (RIP) insulation bushing for converter transformer was designed by the equivalence of maximum electric field, coaxial cylinder structure and RIP materials. The increment law of dielectric parameters both dissipation factor and capacitance at wideband frequency (1mHz ~ 10kHz) was measured for a quality RIP insulation samples at the temperature from 30°C to 100°C. 1) Under the uniform temperature, it was found that the value of dissipation factor was rising with the frequency from 10 Hz to 0.001Hz, while the tendency was reversed at the frequency from 100Hz to10kHz. 2) The minimum value of tan $\delta $ from 0.001Hz to 10kHz could be driven to higher frequency moving (10Hz to 10kHz) by the action of temperature rising 30°C to 100°C.3) The effect of temperature on the lower frequency 0.001Hz ~ 1Hz tan $\delta $ of RIP insulation closely conformed to the index law of Arrhenius equation, while it was in accordance with the linear decrease at higher frequency 1kHz ~ 10kHz. The effect of temperature on dissipation factor could be eliminated by curve segment shifting based the experiment equation, which it at 0.001Hz dissipation factor could be eliminated by curve shifting based the index equation originated Arrhenius equation. The method is beneficial to eliminate the influence of temperature on the dielectric spectroscopy test results, and then to eliminate the influence of temperature on the dielectric spectroscopy diagnosis of RIP bushings.

With the rapid development of online social networks, text-communication has become an indispensable part of daily life. Mining the emotion hidden behind the conversation-text is of prime significance and application value when it comes to the government public-opinion supervision, enterprise decision-making, etc. Therefore, in this paper, we propose a text emotion prediction model in a multi-participant text-conversation scenario, which aims to effectively predict the emotion of the text to be posted by target speaker in the future. Specifically, first, an affective space mapping is constructed, which represents the original conversation-text as an n-dimensional affective vector so as to obtain the text representation on different emotion categories. Second, a similar scene search mechanism is adopted to seek several sub-sequences which contain similar tendency on emotion shift to that of the current conversation scene. Finally, the text emotion prediction model is constructed in a two-layer encoder-decoder structure with the emotion fusion and hybrid attention mechanism introduced at the encoder and decoder side respectively. According to the experimental results, our proposed model can achieve an overall best performance on emotion prediction due to the auxiliary features extracted from similar scenes and the adoption of emotion fusion as well as the hybrid attention mechanism. At the same time, the prediction efficiency can still be controlled at an acceptable level.

Abstract. Serving as the interface between the fetal and maternal environments during gestation, the placenta plays critical roles in the protection of the developing fetus and the maintenance of maternal health. The placenta is primarily derived from the embryonic trophectoderm which differentiates into various subtypes of trophoblast cells through villous and extravillous pathways. The interactions among trophoblasts and multiple decidual cells and immune cells at the maternal-fetal interface fundamentally form the functional units of the placenta, which are responsible for blood perfusion and maternal-fetal material exchange, immune tolerance, and the regulation of pregnancy adaptation. Defects in placental development and functional maintenance are in tight association with adverse pregnancy outcomes such as preeclampsia. In this article, we review recent advances on human trophoblast cell differentiation and the construction of placental functional units and discuss the placental and maternal factors that may contribute to the occurrence of preeclampsia.

BackgroundAfter the rapid spread of the novel SARS-CoV-2, the short-term and long-term mental health impacts of the pandemic on the public, in particular on susceptible individuals, have been reported worldwide. Although digital mental health services expand accessibility while removing many barriers to in-person therapy, their usability, feasibility, acceptability, and efficacy require continued monitoring during the initial phase of the pandemic and its aftermath. ObjectiveIn this study, we aimed to understand what mental health services are offered, whether they are practical or acceptable, and to what extent digital mental health services are effective in response to the COVID-19 pandemic across high-income and low- and middle-income countries. MethodsThis study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guideline. We implemented searches in PubMed (MEDLINE), Embase, PsycINFO, and Cochrane databases for studies that were published between December 2019 and November 2021 and that involved the use of digital mental health services. Two review authors screened, assessed, and extracted studies independently. The protocol was registered on the International Prospective Register of Systematic Reviews. ResultsThis review identified 7506 articles through database searching. In total, 65 (0.9%) studies from 18 countries with 67,884 participants were eligible for the scoping review. Of the 65 studies, 16 (24.6%) were included in the meta-analysis. A total of 15 (23.1%) studies measured the usability; 31 (47.7%) studies evaluated the feasibility; 29 (44.6%) studies assessed the acceptability; and 51 (78.5%) studies assessed the efficacy. Web-based programs (21/65, 32.3%), videoconferencing platforms (16/65, 24.6%), smartphone apps (14/65, 21.5%), and SMS text messaging (5/65, 7.7%) were the main techniques. Psychotherapy (44/65, 67.7%) followed by psychoeducation (6/65, 9.2%) and psychological support (5/65, 7.7%) were commonly used. The results of the meta-analysis showed that digital mental health interventions were associated with a small reduction in depressive symptoms (standardized mean difference=−0.49; 95% CI −0.74 to −0.24; P

The life history approach, a common interviewing method within the social sciences, involves collecting longitudinal data retrospectively by seeking an individual’s account of their life over different periods of time. The exploratory, in-depth and narrative nature of life history interviews make it a compelling narrative method that can illicit rich and in-depth data and understanding (of the “other” and self). At the same time, this attribute raises various ethical complexities that must be considered. This paper documents the personal and professional reflections of a research team conducting life history interviews for a specific research project. It highlights the value of life history interview as a narrative method, and discusses the ethical complexities that can arise.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) accounts for 70% of the total number of patients with cleft lip with or without cleft palate (CL/P) and is the most common type of congenital deformity of the craniomaxillofacial region. In this study, whole exome sequencing (WES) and Sanger sequencing were performed on affected members of a Han Chinese family, and a missense variant in the platelet-derived growth factor C (PDGFC) gene (NM_016205: c.G93T: p.Q31H) was identified to be associated with NSCL/P. Bioinformatic studies demonstrated that the amino acid corresponding to this variation is highly conserved in many mammals and leads to a glutamine-to-histidine substitution in an evolutionarily conserved DNA-binding domain. It was found that the expression of PDGFC was significantly decreased in the dental pulp stem cells (DPSCs) of NSCL/P cases, compared to the controls, and that the variant (NM_016205: c.G93T) reduced the expression of PDGFC. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that Pdgfc deficiency disrupted NSCL/P-related signaling pathways such as the MAPK signaling pathway and cell adhesion molecules. In conclusion, our study identified a missense variant (NM_016205: c.G93T) in exon 1 of PDGFC potentially associated with susceptibility to NSCL/P.

F-actin (filamentous actin) has been shown to be sensitive to mechanical stimuli and play critical roles in cell attachment, migration, and cancer metastasis, but there are very limited ways to perturb F-actin dynamics with low cell toxicity. Magnetic field is a noninvasive and reversible physical tool that can easily penetrate cells and human bodies. Here, we show that 0.1/0.4-T 4.2-Hz moderate-intensity low-frequency rotating magnetic field-induced electric field could directly decrease F-actin formation in vitro and in vivo, which results in decreased breast cancer cell migration, invasion, and attachment. Moreover, low-frequency rotating magnetic fields generated significantly different effects on F-actin in breast cancer vs. noncancerous cells, including F-actin number and their recovery after magnetic field retrieval. Using an intermittent treatment modality, low-frequency rotating magnetic fields could significantly reduce mouse breast cancer metastasis, prolong mouse survival by 31.5 to 46.0% (P < 0.0001), and improve their overall physical condition. Therefore, our work demonstrates that low-frequency rotating magnetic fields not only can be used as a research tool to perturb F-actin but also can inhibit breast cancer metastasis through F-actin modulation while having minimum effects on normal cells, which reveals their potential to be developed as temporal-controlled, noninvasive, and high-penetration physical treatments for metastatic cancer.