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Abstract Background Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood. Methods To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP). Results Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression. Conclusions Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.

Abstract Background Severe pneumonia has consistently been associated with high mortality. We sought to identify risk factors for the mortality of severe pneumonia to assist in reducing mortality for medical treatment. Methods Electronic databases including PubMed, Web of Science, EMBASE, Cochrane Library, and Scopus were systematically searched till June 1, 2023. All human research were incorporated into the analysis, regardless of language, publication date, or geographical location. To pool the estimate, a mixed-effect model was used. The Newcastle–Ottawa Scale (NOS) was employed for assessing the quality of included studies that were included in the analysis. Results In total, 22 studies with a total of 3655 severe pneumonia patients and 1107 cases (30.29%) of death were included in the current meta-analysis. Significant associations were found between age [5.76 years, 95% confidence interval [CI] (3.43, 8.09), P

Abstract Background Extracorporeal membrane oxygenation (ECMO) is a cutting-edge life-support measure for patients with severe cardiac and pulmonary illnesses. Although there are several systematic reviews (SRs) about ECMO, it remains to be seen how quality they are and how efficacy and safe the information about ECMO they describe is in these SRs. Therefore, performing an overview of available SRs concerning ECMO is crucial. Methods We searched four electronic databases from inception to January 2023 to identify SRs with or without meta-analyses. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were used to assess the methodological quality, and evidence quality for SRs, respectively. A bubble plot was used to visually display clinical topics, literature size, number of SRs, evidence quality, and an overall estimate of efficacy. Results A total of 17 SRs met eligibility criteria, which were combined into 9 different clinical topics. The methodological quality of the included SRs in this mapping was “Critically low” to “Moderate”. One of the SRs was high-quality evidence, three on moderate, three on low, and two on very low-quality evidence. The most prevalent study used to evaluate ECMO technology was observational or cohort study with frequently small sample sizes. ECMO has been proven beneficial for severe ARDS and ALI due to the H1N1 influenza infection. For ARDS, ALF or ACLF, and cardiac arrest were concluded to be probably beneficial. For dependent ARDS, ARF, ARF due to the H1N1 influenza pandemic, and cardiac arrest of cardiac origin came to an inconclusive conclusion. There was no evidence for a harmful association between ECMO and the range of clinical topics. Conclusions There is limited available evidence for ECMO that large sample, multi-center, and multinational RCTs are needed. Most clinical topics are reported as beneficial or probably beneficial of SRs for ECMO. Evidence mapping is a valuable and reliable methodology to identify and present the existing evidence about therapeutic interventions.

Diarrheagenic Escherichia coli serotypes are associated with various clinical syndromes, yet the precise correlation between serotype and pathotype remains unclear. A major barrier to such studies is the reliance on antisera-based serotyping, which is culture-dependent, low-throughput, and cost-ineffective. We have established a highly multiplex PCR-based serotyping assay, termed the MeltArray E. coli serotyping (EST) assay, capable of identifying 163 O-antigen-encoding genes and 53 H-antigen-encoding genes of E. coli. The assay successfully identified serotypes directly from both simulated and real fecal samples, as demonstrated through spike-in validation experiments and a retrospective study. In a multi-province study involving 637 E. coli strains, it revealed that the five major diarrheagenic pathotypes have distinct serotype compositions. Notably, it differentiated 257 Shigella isolates into four major Shigella species, distinguishing them from enteroinvasive E. coli based on their distinct serotype profiles. The assay’s universality was further corroborated by in silico analysis of whole-genome sequences from the EnteroBase. We conclude that the MeltArray EST assay represents a paradigm-shifting tool for molecular serotyping of E. coli, with potential routine applications for comprehensive serotype analysis, disease diagnosis, and outbreak detection.

China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.

SignificanceAgricultural machinery serves as the fundamental support for implementing advanced agricultural production concepts. The key challenge for the future development of smart agriculture lies in how to enhance the design, manufacturing, operation, and maintenance of these machines to fully leverage their capabilities. To address this, the concept of the digital twin has emerged as an innovative approach that integrates various information technologies and facilitates the integration of virtual and real-world interactions. By providing a deeper understanding of agricultural machinery and its operational processes, the digital twin offers solutions to the complexity encountered throughout the entire lifecycle, from design to recycling. Consequently, it contributes to an all-encompassing enhancement of the quality of agricultural machinery operations, enabling them to better meet the demands of agricultural production. Nevertheless, despite its significant potential, the adoption of the digital twin for agricultural machinery is still at an early stage, lacking the necessary theoretical guidance and methodological frameworks to inform its practical implementation.ProgressDrawing upon the successful experiences of the author's team in the digital twin for agricultural machinery, this paper presents an overview of the research progress made in digital twin. It covers three main areas: The digital twin in a general sense, the digital twin in agriculture, and the digital twin for agricultural machinery. The digital twin is conceptualized as an abstract notion that combines model-based system engineering and cyber-physical systems, facilitating the integration of virtual and real-world environments. This paper elucidates the relevant concepts and implications of digital twin in the context of agricultural machinery. It points out that the digital twin for agricultural machinery aims to leverage advanced information technology to create virtual models that accurately describe agricultural machinery and its operational processes. These virtual models act as a carrier, driven by data, to facilitate interaction and integration between physical agricultural machinery and their digital counterparts, consequently yielding enhanced value. Additionally, it proposes a comprehensive framework comprising five key components: Physical entities, virtual models, data and connectivity, system services, and business applications. Each component's functions operational mechanism, and organizational structure are elucidated. The development of the digital twin for agricultural machinery is still in its conceptual phase, and it will require substantial time and effort to gradually enhance its capabilities. In order to advance further research and application of the digital twin in this domain, this paper integrates relevant theories and practical experiences to propose an implementation plan for the digital twin for agricultural machinery. The macroscopic development process encompasses three stages: Theoretical exploration, practical application, and summarization. The specific implementation process entails four key steps: Intelligent upgrading of agricultural machinery, establishment of information exchange channels, construction of virtual models, and development of digital twin business applications. The implementation of digital twin for agricultural machinery comprises four stages: Pre-research, planning, implementation, and evaluation. The digital twin serves as a crucial link and bridge between agricultural machinery and the smart agriculture. It not only facilitates the design and manufacturing of agricultural machinery, aligning them with the realities of agricultural production and supporting the advancement of advanced manufacturing capabilities, but also enhances the operation, maintenance, and management of agricultural production to better meet practical requirements. This, in turn, expedites the practical implementation of smart agriculture. To fully showcase the value of the digital twin for agricultural machinery, this paper addresses the existing challenges in the design, manufacturing, operation, and management of agricultural machinery. It expounds the methods by which the digital twin can address these challenges and provides a technical roadmap for empowering the design, manufacturing, operation, and management of agricultural machinery through the use of the digital twin. In tackling the critical issue of leveraging the digital twin to enhance the operational quality of agricultural machinery, this paper presents two research cases focusing on high-powered tractors and large combine harvesters. These cases validate the feasibility of the digital twin in improving the quality of plowing operations for high-powered tractors and the quality of grain harvesting for large combine harvesters.Conclusions and ProspectsThis paper serves as a reference for the development of research on digital twin for agricultural machinery, laying a theoretical foundation for empowering smart agriculture and intelligent equipment with the digital twin. The digital twin provides a new approach for the transformation and upgrade of agricultural machinery, offering a new path for enhancing the level of agricultural mechanization and presenting new ideas for realizing smart agriculture. However, existing digital twin for agricultural machinery is still in its early stages, and there are a series of issues that need to be explored. It is necessary to involve more professionals from relevant fields to advance the research in this area.

Abstract Background To explore the causes of endoscopic misdiagnosis of gastrointestinal cyst as solid lesion and the diagnostic value and limitations of EUS, guide clinicians to develop appropriate treatment strategies and improve the ability to identify SMT. Methods We enrolled patients diagnosed with gastrointestinal SMT between January 2001 and December 2021 who underwent endoscopic resection with postoperative pathological diagnosis of cyst. Age, sex, maximum lesion diameter, judge the texture of lesion, origin and echo are potential factors affecting the diagnostic accuracy of cysts. Results The diagnostic accuracy of EUS assessment 39.3% higher than that without EUS assessment (6.7%). The error rate was 60.7%, lower than that without EUS assessment (93.3%), suggesting that preoperative EUS assessment improved the diagnostic accuracy of gastrointestinal cyst (Fisher's accurate test, P = 0.033). The diagnostic accuracy of “judge the texture of lesion” was higher than that of no touch (P = 0.031). When the lesion size increased by 1 cm, the diagnostic accuracy decreased by about 21%. Hypoechoic lesions were less likely to be diagnosed correctly than anechoic lesions (P = 0.003). Conclusions The main cause of misdiagnosing gastrointestinal cyst as solid lesion is that no EUS assessment was performed before endoscopic resection or anechoic lesion was judged as hypoechoic lesion by preoperative EUS assessment.

Background: Previous studies revealed associations between air-pollutant exposure and in vitro fertilization (IVF) outcomes. However, modification effects of air pollution on IVF outcomes by meteorological conditions remain elusive. Methods: This multicenter retrospective cohort study included 15,217 women from five northern Chinese cities during 2015–2020. Daily average concentrations of air pollutants (PM2.5, PM10, O3, NO2, SO2, and CO) and meteorological factors (temperature, relative humidity, wind speed, and sunshine duration) during different exposure windows were calculated as individual approximate exposure. Generalized estimating equations models and stratified analyses were conducted to assess the associations of air pollution and meteorological conditions with IVF outcomes and estimate potential interactions. Results: Positive associations of wind speed and sunshine duration with pregnancy outcomes were detected. In addition, we observed that embryo transfer in spring and summer had a higher likelihood to achieve a live birth compared with winter. Exposure to PM2.5, SO2, and O3 was adversely correlated with pregnancy outcomes in fresh IVF cycles, and the associations were modified by air temperature, relative humidity, and wind speed. The inverse associations of PM2.5 and SO2 exposure with biochemical pregnancy were stronger at lower temperatures and humidity. Negative associations of PM2.5 with clinical pregnancy were only significant at lower temperatures and wind speeds. Moreover, the effects of O3 on live birth were enhanced by higher wind speed. Conclusions: Our results suggested that the associations between air-pollutant exposure and IVF outcomes were modified by meteorological conditions, especially temperature and wind speed. Women undergoing IVF treatment should be advised to reduce outdoor time when the air quality was poor, particularly at lower temperatures.

The relationship between satellite thermal infrared anomalies and earthquakes or fault activity has been studied for more than 30 years. In this study, five strong earthquakes (the MS6.1 earthquake in Biru, Tibet; the MS7.4 earthquake in Madoi, Qinghai; the MS6.0 earthquake in Delingha, Qinghai; the MS6.1 earthquake in Lushan, Sichuan; and the MS6.8 earthquake in Luding, Sichuan) that occurred on the western mainland of China over the past 2 years were studied. Based on monthly MODIS land surface temperature (LST) data and daily NOAA satellite longwave radiation data, the departure algorithm and the Robust Satellite Techniques (RST) algorithm were used to extract and analyze the characteristics of thermal infrared anomaly information for blocks and faults around the earthquake from different temporal and spatial scales. The results showed the following: 1) In the medium-term scale study based on monthly data, blocks near the epicenters of five earthquakes showed temperature increase anomalies of 1–6 months before the earthquakes; the areas of temperature increase anomalies were clearly controlled by the spatial distribution of the blocks, and earthquakes mostly occurred within blocks with frequent temperature increase anomalies. 2) In the short-term, thermal infrared anomaly feature tracking based on daily data meant that obvious thermal anomalies were also found. The thermal anomalies before the five seismic events all appeared within a period of 3 months before the earthquake, and there were multiple consecutive days of anomalies. The significant temperature increases generally occurred a month before the earthquake, and the distribution of the anomalies was mostly in the form of strips, which is basically consistent with the trend of the fault zone. The use of thermal infrared remote sensing data to summarize the dynamic evolution of thermal infrared anomalies of blocks and faults before strong earthquakes can provide a basis for the long-term monitoring of fault activity and seismic monitoring by satellite thermal infrared technology.

Some fast radio bursts (FRBs) exhibit repetitive behaviors, and their origins remain enigmatic. It has been argued that repeating FRBs could be produced by the interaction between a neutron star and an asteroid belt. Here, we consider the systems in which an asteroid belt dwells around a massive star, while a neutron star, as a companion of the massive star, interacts with the belt through gravitational force. Various orbital configurations are assumed for the system. Direct N -body simulations are performed to investigate the dynamical evolution of the asteroids' belt. It is found that a larger orbital eccentricity of the neutron star will destroy the belt more quickly, with a large number of asteroids being scattered out of the system. A low inclination not only suppresses the collisions but also inhibits the ejection rate at early stages. However, highly inclined systems may undergo strong oscillations, resulting in the Kozai–Lidov instabilities. Among the various configurations, a clear periodicity is observed in the collision events for the case with an orbital eccentricity of 0.7 and mutual inclination of 0 ^◦ . It is found that such a periodicity can be sustained for at least eight neutron star orbital periods, supporting this mechanism as a possible explanation for periodically repeating FRBs. Our studies also suggest that the active stage of these kinds of FRB sources should be limited, since the asteroid belt would finally be destroyed by the neutron star after multiple passages.

In this study, the co-combustion of coal and biomass, and the tri-combustion of coal, biomass, and oil sludge in a 130 t h−1 circulating fluidized bed (CFB) boiler are investigated via the computational particle fluid dynamics (CPFD) approach. Furthermore, the effect of biomass feeding position is also comprehensively evaluated. The results show that for the co-combustion of coal and biomass, the O2 mole fraction at the furnace outlet rises from 0.0541 to 0.0640 as the biomass blending ratio enhances from 40% to 100%, while the CO2 mole fraction reduces from 0.1357 to 0.1267. The mole fraction of NOx and SO2 at the furnace outlet decreases from 4.5867 × 10−5 to 3.9096 × 10−5 and 2.8253 × 10−4 to 4.6635 × 10−5, respectively. For the tri-combustion of three fuels, the average NOx mole fraction initially grows quickly and then declines gradually, ranging from 4.1173 × 10−5 to 4.2556 × 10−5. The mole fraction of SO2 at the furnace outlet increases from 3.5176 × 10−4 to 4.7043 × 10−4 when the ratio of oil sludge rises from 10% to 20%. The uniformity of temperature and gas components distribution is “new inlet > secondary air inlet > feed inlet”. As for the three inlet positions, the mole fractions of NOx at the furnace outlet are between 3.9096 × 10−5 and 5.1537 × 10−5, while those for SO2 are between 2.5978 × 10−4 and 2.5278 × 10−4.

Kinesin family member17 (KIF17), a homologous dimer of the kinesin-2 protein family, has important microtubule-dependent and -independent roles in spermiogenesis. Little is known about KIF17 in the mollusk, Phascolosoma esculenta, a newly developed mariculture species in China. Here, we cloned the open reading frame of Pe-kif17 and its related gene, Pe-act, and performed bioinformatics analysis on both. Pe-KIF17 and Pe-ACT are structurally conserved, indicating that they may be functionally conserved. The expression pattern of kif17/act mRNA performed during spermiogenesis revealed their expression in diverse tissues, with the highest expression level in the coelomic fluid of P. esculenta. The expressions of Pe-kif17 and Pe-act mRNA were relatively high during the breeding season (July–September), suggesting that Pe-KIF17/ACT may be involved in spermatogenesis, particularly during spermiogenesis. Further analysis of Pe-kif17 mRNA via fluorescence in situ hybridization revealed the continuous expression of this mRNA during spermiogenesis, suggesting potential functions in this process. Immunofluorescence showed that Pe-KIF17 co-localized with α-tubulin and migrated from the perinuclear cytoplasm to one side of the spermatid, forming the sperm tail. Pe-KIF17 and Pe-ACT also colocalized. KIF17 may participate in spermiogenesis of P. esculenta, particularly in nuclear reshaping and tail formation by interacting with microtubule structures similar to the manchette. Moreover, Pe-KIF17 with Pe-ACT is also involved in nuclear reshaping and tail formation in the absence of microtubules. This study provides evidence for the role of KIF17 during spermiogenesis and provides theoretical data for studies of the reproductive biology of P. esculenta. These findings are important for spermatogenesis in mollusks.

Abstract. Background:. Pancreatitis is a common disease of the digestive system. Acute pancreatitis is one of the most common reasons for gastrointestinal hospital admission, and chronic pancreatitis significantly reduces quality of life. However, national epidemiological data on pancreatitis in China are lacking. This study aimed to quantify the disease burden of pancreatitis in China from 1990 to 2019. Methods:. This study was based on the Global Burden of Disease Study 2019 dataset. Age-standardized rates of incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALYs) were used to describe the disease burden of pancreatitis, and estimated annual percentage change (EAPC) was used to indicate the average change in age-standardized rates. We also described the trend of pancreatitis-related mortality and DALYs, which are attributable to alcohol use by age and sex. Results:. From 1990 to 2019, the ASIR, ASPR, ASMR, and age-standardized DALYs of pancreatitis in China decreased by 10.90, 1.50, 0.49, and 15.54 per 100,000, respectively, with EAPCs of −1.35 (95% uncertainty interval [UI]: −1.67, −1.02) and −0.37 (95% UI: −0.43, −0.31), −2.01 (95% UI: −2.07, −1.94) and −2.32 (95% UI: −2.37, −2.28), respectively. Recently, the numbers of incident and prevalent cases have risen, with estimates of 380,018 (95% UI: 308,669–462,767) and 493,765 (95% UI: 416,705–578,675), respectively, in 2019. Among men, the disease burden of pancreatitis was more severe than among women, and with variances in the distribution among different age groups. Age-standardized DALYs caused by alcohol-related pancreatitis have gradually worsened in the past decade, accounting for 34.09% of the total in 2019. Conclusions:. The disease burden of pancreatitis in China has declined in the past 30 years, but the exacerbation of population aging poses a challenge to prevention and control of pancreatitis. Alcohol use has gradually become an important factor in the disease burden of pancreatitis in recent years.

IntroductionRare genetic diseases are a major cause for severe illness in children. Whole exome sequencing (WES) is a powerful tool for identifying genetic causes of rare diseases. For a better and faster assessment of the vast number of variants that are identified in the index patient in WES, parental sequencing can be applied (“trio WES”).MethodsWe assessed the diagnostic rate of routine trio WES including analysis of copy number variants in 224 pediatric patients during an evaluation period of three years.ResultsTrio WES provided a diagnosis in 67 (30%) of all 224 analysed children. The turnaround time of trio WES analysis has been reduced significantly from 41 days in 2019 to 23 days in 2021. Copy number variants could be identified to be causative in 10 cases (4.5%), underlying the importance of copy number variant analysis. Variants in three genes which were previously not associated with a clinical condition (GAD1, TMEM222 and ZNFX1) were identified using the matching tool GeneMatcher and were part of the first description of a new syndrome.DiscussionTrio WES has proven to have a high diagnostic yield and to shorten the process of identifying the correct diagnosis in paediatric patients. Re-evaluation of all 224 trio WES 1–3 years after initial analysis did not establish new diagnoses. Initiating (trio) WES as a first-tier diagnostics including copy number variant detection should be considered as early as possible, especially for children treated in ICU, if a monogenetic disease is suspected.

IntroductionThe most frequent complications after abdominal surgery include a decrease or loss of appetite, abdominal distension, abdominal pain caused by reduced gastrointestinal motility, anal arrest with intestinal distension and defecation, and nausea and vomiting due to anesthetic and opioid analgesic administration. These complications severely affect postoperative recovery, prolong hospital stay, and increase the financial burden. The objective of this study is to investigate the efficacy and safety of three acupoint stimulation modalities (electroacupuncture [EA], transcutaneous electrical acupoint stimulation [TEAS], and transcutaneous acupoint electrical stimulation combined with EA [TEAS+EA]), and two EA instrument waveforms (continuous wave and dilatational wave) for rapid recovery after abdominal surgery.Methods and analysisA total of 560 patients will be recruited and randomly allocated to receive one of the following seven interventions: continuous wave EA, continuous wave TEAS, continuous wave TEAS + EA, dilatational wave EA, dilatational wave TEAS, dilatational wave TEAS + EA, and a control. For this study, continuous waves at 2 Hz, and dilatational waves at 2/50 Hz would be selected. The points to be stimulated by EA are the bilateral Neiguan (PC6), Hegu (LI6), Zusanli (ST36), Shangjuxu (ST37), and Xiajuxu (ST39), and TEAS would stimulate the bilateral Liangmen (ST21) and Daheng (SP15). The control group will neither receive EA nor TEAS. All patients will undergo an enhanced recovery plan after surgery and be provided with standardized perioperative management. Treatment will start on the first postoperative day and be administered once daily in the morning until the patient regains spontaneous bowel movements and can tolerate oral intake of solid food. The primary outcome is a composite of time to first defecation and time to tolerance of a solid diet. Secondary outcomes include time to first exhaustion; time of first defecation; time of tolerance of a solid diet; time to the first ambulation; length of hospital stay from surgery to discharge; visual analog scale score for postoperative daily pain, nausea, and vomiting; incidence of postoperative complications; and treatment acceptability.DiscussionThis study will compare the efficacy and safety of three acupoint stimulation methods and two EA instrument waveforms for rapid recovery after abdominal surgery.Trial RegistrationChinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2100043883.

Mitochondria are essential for spermiogenesis. Prohibitins (PHBs; prohibitin 1, PHB1 or PHB, and prohibitin 2, PHB2) are evolutionarily conserved and ubiquitously expressed mitochondrial proteins that act as scaffolds in the inner mitochondrial membrane. In this study, we analyzed the molecular structure and dynamic expression characteristics of Ot-PHBs, observed the colocalization of Ot-PHB1 with mitochondria and polyubiquitin, and studied the effect of phb1 knockdown on mitochondrial DNA (mtDNA) content, reactive oxygen species (ROS) levels, and apoptosis-related gene expression in spermatids. Our aim was to explore the effect of Ot-PHBs on mitochondrial function during the spermiogenesis of Octopus tankahkeei (O. tankahkeei), an economically important species in China. The predicted Ot-PHB1/PHB2 proteins contained an N-terminal transmembrane, a stomatin/prohibitin/flotillin/HflK/C (SPFH) domain (also known as the prohibitin domain), and a C-terminal coiled-coil domain. Ot-phb1/phb2 mRNA were widely expressed in the different tissues, with elevated expression in the testis. Further, Ot-PHB1 and Ot-PHB2 were highly colocalized, suggesting that they may function primarily as an Ot-PHB compiex in O. tankahkeei. Ot-PHB1 proteins were mainly expressed and localized in mitochondria during spermiogenesis, implying that their function may be localized to the mitochondria. In addition, Ot-PHB1 was colocalized with polyubiquitin during spermiogenesis, suggesting that it may be a polyubiquitin substrate that regulates mitochondrial ubiquitination during spermiogenesis to ensure mitochondrial quality. To further investigate the effect of Ot-PHBs on mitochondrial function, we knocked down Ot-phb1 and observed a decrease in mtDNA content, along with increases in ROS levels and the expressions of mitochondria-induced apoptosis-related genes bax, bcl2, and caspase-3 mRNA. These findings indicate that PHBs might influence mitochondrial function by maintaining mtDNA content and stabilizing ROS levels; in addition, PHBs might affect spermatocyte survival by regulating mitochondria-induced apoptosis during spermiogenesis in O. tankahkeei.

Summary: Background: Human evidence on the association between air pollution and ovarian response is scarce. Poor ovarian response (POR) with an incidence of 5–35% is a tricky problem in IVF treatment. Methods: In this large-scale multicentre study, we included 2186 women with POR (< 4 oocytes retrieved) and 7033 women with a normal ovarian response (10–15 oocytes retrieved), who underwent their first in vitro fertilization treatment in five cities in northern China during 2015–2020. Average concentrations of six air pollutants (PM2.5, PM10, O3, NO2, CO, and SO2) during different exposure windows (5 days, 1, 3, 6, and 12 months) before oocyte pick up (OPU) were calculated using data from the air monitoring station nearest to the residential site as approximate individual exposure. Logistic regression models were employed to assess the association between exposure to air pollutants and the risk of POR. Stratification analyses were conducted based on female age. Sensitivity analyses were performed in poor responders identified by Bologna criteria and women with unexpected POR. Findings: We detected that increased SO2 exposure during all exposure windows before OPU was associated with a higher risk of POR, especially for women ≤ 30 years old. In the stratified analysis, the effect sizes were larger for the unexpected poor ovarian response. Interpretation: The findings provide human evidence for adverse effects of exposure to ambient air pollutants on ovarian response and underscore the need to reduce ambient air pollution exposure in women of reproductive age to protect human fertility. Funding: This study was granted from the National Key Research and Development Program (2018YFC1004203), the Major Special Construction Plan for Discipline Construction Project of China Medical University (3110118033), the Shengjing Freelance Researcher Plan of Shengjing Hospital of China Medical University, and the National Natural Science Foundation of China (82071601), the Central Government Special Fund for Local Science and Technology Development (2020JH6/10500006).

Since 2010, porcine epidemic diarrhea virus (PEDV) has swept across China and spread throughout the country, causing huge economic losses. In this study, 673 diarrhea samples from 143 pig farms in Guangxi during 2017–2022 were collected and detected for PEDV. Ninety-eight strains were selected for S1 gene analyses and these strains were classified into four subgroups (G1b, G2a, G2b and G2c), accounting for 1.02 (1/98), 75.51 (74/98), 16.33 (16/98) and 7.14% (7/98) of the total, respectively. Importantly, an increased number of strains in the G2c subgroup was found from 2019 onwards. Bayesian analysis revealed that Guigang may have been the epicenter of PEDVs in Guangxi. In addition, Guigang was identified as the primary hub from which PEDVs spread via two routes, namely Guigang–Wuzhou and Guigang–Laibin. Moreover, several coinfections of novel PEDV variants bearing large deletions in the partial S1 protein and PEDVs possessing an intact partial S1 protein were found in pigs. Further recombination analyses indicated that two of the strains, 18-GXNN-6 and 19-GXBH-2, originated from intra-genogroup recombination. Together, our data revealed a new profile of PEDV in Guangxi, China, which enhances our understanding of the distribution, genetic characteristics and evolutionary profile of the circulating PEDV strains in China.

Eating behaviors are a set of cognitive processes that influence dietary decision making and, thus, overall health. Some of the most studied eating behaviors are those characterized by the Three Factor Eating Questionnaire-18 (TFEQ). The TFEQ examines three eating behaviors: emotional eating (EE), uncontrolled eating (UE), and restrained eating (RE). While frequently used, there is little information characterizing these eating behaviors in the Ghanaian population. This cross-sectional study describes EE, UE, and RE behaviors in a university student population (n = 129) in Ghana. Of the three behaviors, EE was the only one associated with any of the health outcomes in this study: BMI for males (r = 0.388, p = 0.002) and anxiety (r = 0.471, p < 0.001, higher score is less desirable), and sleep quality (r = 0.464, p < 0.001, higher score is less desirable) for females. Overweight and obese females reported significantly higher EE scores compared to healthy weight females (35.7 ± 23.7 vs. 11.9 ± 15.6, p = 0.002). No such observation was observed among overweight and obese males (p > 0.05). EE, UE, and RE scores did not differ between males and females. While this study provides important information about the eating behaviors of Ghanaian university students and allows for comparison to students from other cultures, future work must develop culturally relevant tools for the Ghanaian population.

Health behaviors of higher education students can be negatively influenced by stressful events. The global COVID-19 pandemic presents a unique opportunity to characterize and compare health behaviors across multiple countries and to examine how these behaviors are shaped by the pandemic experience. Undergraduate and graduate students enrolled in universities in China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands and the United States (USA) were recruited into this cross-sectional study. Eligible students filled out an online survey comprised of validated tools for assessing sleep quality and duration, dietary risk, alcohol misuse and physical activity between late April and the end of May 2020. Health behaviors were fairly consistent across countries, and all countries reported poor sleep quality. However, during the survey period, the COVID-19 pandemic influenced the health behaviors of students in European countries and the USA more negatively than Asian countries, which could be attributed to the differences in pandemic time course and caseloads. Students who experienced a decline in sleep quality during the COVID-19 pandemic had higher dietary risk scores than students who did not experience a change in sleep quality (p = 0.001). Improved sleep quality was associated with less sitting time (p = 0.010). Addressing sleep issues among higher education students is a pressing concern, especially during stressful events. These results support the importance of making education and behavior-based sleep programming available for higher education students in order to benefit students’ overall health.

Genomic selection in plants and animals has become a standard tool for breeding because of the advantages of high accuracy and short generation intervals. Implementation of this technology is hindered by the high cost of genotyping and other factors. The aim of this study was to determine an optional marker density panel and reference population size for using genomic selection of goats, with speculation on the number of QTLs that affect the important economic traits of goats. In addition, the effect of buck population size in the reference population on the accuracy of genomic estimated breeding value (GEBV) was discussed. Based on the previous genetic evaluation results of Inner Mongolia White Cashmere Goats, live body weight (LBW, h2 = 0.11) and fiber diameter (FD, h2 = 0.34) were chosen to perform genomic selection in this study. Reasonable genome parameters and generation transmission processes were set, and phenotypic and genotype data of the two traits were simulated. Then, different sizes of the reference population and validation population were selected from progeny. The GEBVs were obtained by six methods, including GBLUP (Genomic Best Linear Unbiased Prediction), ssGBLUP (Single Step Genomic Best Linear Unbiased Prediction), BayesA, BayesB, Bayesian ridge regression, and Bayesian LASSO. The correlation coefficient between the predicted and realized phenotypes from simulation was calculated and used as a measure of the accuracy of GEBV in each trait. The results showed that the medium marker density Panel (45 K) could be used for genomic selection in goats, which can ensure the accuracy of the GEBV. The reference population size of 1,500 can achieve greater genetic progress in genomic selection for fiber diameter and live body weight in goats by comparing with the population size below this level. The accuracy of the GEBV for live body weight and fiber diameter was better when the number of QTLs was 100 and 50, respectively. Additionally, the accuracy of GEBV was discovered to be good when the buck population size was up to 200. Meanwhile, the accuracy of the GEBV for medium heritability traits (FDs) was found to be higher than the accuracy of the GEBV for low heritability traits (LBWs). These findings will provide theoretical guidance for genomic selection in goats by using real data.

Abstract Background Accumulating evidence supports that lysine-specific demethylase 5 (KDM5) family members act as oncogenic drivers. This study was performed to elucidate the potential effects of KDM5A on prostate cancer (PCa) progression via the miR-495/YTHDF2/m6A-MOB3B axis. Methods The expression of KDM5A, miR-495, YTHDF2 and MOB3B was validated in human PCa tissues and cell lines. Ectopic expression and knockdown experiments were developed in PCa cells to evaluate their effects on PCa cell proliferation, migration, invasion and apoptosis. Mechanistic insights into the interaction among KDM5A, miR-495, YTHDF2 and MOB3B were obtained after dual luciferase reporter, ChIP, and PAR-CLIP assays. Me-RIP assay was used to determine m6A modification level of MOB3B mRNA in PCa cells. Mouse xenograft models of PCa cells were also established to monitor the tumor growth. Results KDM5A was highly expressed in human PCa tissues and cell lines. Upregulated KDM5A stimulated PCa cell proliferation, migration and invasion, but reduced cell apoptosis. Mechanistically, KDM5A, as a H3K4me3 demethylase, bound to the miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. Furthermore, KDM5A was found to downregulate MOB3B expression, consequently augmenting PCa cell proliferation, migration and invasion in vitro and promoting tumor growth in vivo via the miR-495/YTHDF2 axis. Conclusion In summary, our study highlights the potential of histone demethylase KDM5A activity in enhancing PCa progression, and suggests KDM5A as a promising target for PCa treatment.

High levels of perceived stress and anxiety among university students are a global concern and are known to negatively influence sleep. However, few studies have explored how stress response styles, like psychological resilience and rumination, might alter these relationships. Using validated tools, perceived stress, anxiety, stress response styles, and sleep behaviors of undergraduate and graduate students from seven countries during the height of the COVID-19 pandemic were characterized in order to examine the relationships between these factors using mediation and moderation analyses. Students enrolled in universities in China, Ireland, Malaysia, Taiwan, South Korea, the Netherlands, and the United States were recruited in May 2020. A total of 2254 students completed this cross-sectional study. Perceived stress and anxiety were negatively associated with sleep quality through the mediation of rumination. Increased psychological resilience weakened the relationships between perceived stress and anxiety on sleep quality. The majority of students reported that COVID-19 negatively influenced their mental health and sleep quality but not sleep duration. Based on these results, university students would likely benefit from sleep education and mental health promotion programs that include trainings to increase psychological resilience and reduce rumination, particularly during times of increased stress.

In recent years, with the rapid development of new energy and industrial technologies, the solar cell industry has begun to receive considerable attention. Perovskite solar cells are regarded as the third-generation solar cells. As of April 2019, on the basis of the international certification, the maximum power conversion efficiency of perovskite solar cells is 24.2%, which is similar to the highest power conversion efficiency of silicon solar cells. Perovskite solar cells exhibit high power conversion efficiency, low cost, simple preparation, and diversity of structure, which makes them the leaders in next-generation thin-film photovoltaic devices. In this paper the development history of perovskite solar cells was reported; the perovskite crystal structure and device structure were discussed in detail; and a tolerance factor for obtaining a more stable perovskite structure was introduced. We then summarized the A-site, B-site, and X-site composition engineering, the one-step, two-step and other fabrication methods and morphology control methods of perovskite thin films that could stabilize the perovskite crystal structure, reduce the pollution and harm of lead in perovskite films, control the growth of perovskite film, and regulate the band gaps. In addition, the influencing factors on the stability of perovskite solar cells was also discuss; light stability, thermal stability, and humidity stability that are the main causes of the decomposition of perovskite crystals, resulting in a serious decrease in device performance owing to the phase transition and degradation. The biggest obstacle for the industrialization of perovskite solar cells is the stability. Finally a series of methods that can improve the stability of perovskite solar cells were analyzed. The main solutions to the current stability problems of perovskite solar cells include the development of more stable 2D/3D perovskite structures, the development of new additives to control the growth of grains using the interfacial medication methods, and the selection of suitable hole and electron transport materials with superior properties.

In this paper, we developed a novel strategy of preparing doxorubicin (DOX) nanocrystal (NC) exerting spherical particles with a diameter of 102 nm, which experienced following coating of chondroitin sulphate derivative (CSOA) shell via electrostatic and hydrophobic interactions. Such multifunctional outerwear resulted in drug nanocapsules with high drug loading content up to 70% and high colloidal stability under physiological conditions. It exhibited accelerated drug release behaviour when dispersing in hyaluronidase (HAase) containing medium or incubated with cancer cells. CSOA/NCs were effectively taken up by cancer cells via CD44 receptor-mediated endocytosis, but were rarely internalised into normal fibroblasts. With the comparison of typical drug-loaded micelles system (DOX/PEG-PCL), CSOA/NCs showed greater inhibition to cancer cells due to the targeted and sensitive drug delivery.

Mobile-Edge Computing (MEC) addresses the shortcomings of mobile devices in terms of computing performance and energy efficiency by offloading computation tasks to the edge of the network. In this paper, a multi-cell MEC system is considered, where each small cell connects to a common MEC server, and the problem of minimizing system overhead in the MEC system is solved by jointly optimizing the computation offloading decisions, communication and computational resources. This problem is a mixed integer nonlinear programming problem (MINLP). Owning to the combined nature and complexity of this problem, we adopt a method to transform the original problem into two sub-problems: (i) joint optimization computation offloading decision and channel assignment problem (JO-CODCA) and (ii) joint optimization transmission power and computational resource allocation problem (JO-TPCRA). For the transformed sub-problems, we propose a hierarchical optimization method (HIQCO) that combines immune algorithm (IA), quasi-convex optimization and convex optimization techniques. Experimental results show that the proposed HIQCO give better performance comparing with the other compared algorithms in terms of system overhead.

Background: Stress and mental health outcomes are negatively correlated among university students throughout the world. Reports of differences in stress perception by gender exist, but there is limited data on students from sub-Saharan African countries. This study describes the burden of perceived and financial stress; characterizes mood and degree of anxiety symptoms; examines stress coping mechanisms, including resilience and repetitive negative thinking (RNT); and explores how students at a Ghanaian university believed the COVID-19 pandemic affected these measures. Methods: Students (n = 129) were recruited from the Kwame Nkrumah University of Science and Technology, Kumasi, Ghana from October 2020 - January 2021. Validated surveys were used. Participants were asked “Are your answers to the questions affected by the COVID-19 pandemic?” Results: No differences in mean scores were observed between genders. For female students, financial stress was positively associated with RNT (p = 0.009), negative mood (p = 0.002), and anxiety (p < 0.001). Males were more likely to report decreased stress during the pandemic (p = 0.002), but there was no difference in mental health outcomes by perceived stress (PS) change category among males. Effects of the pandemic on mental health outcomes were mixed, but substantial proportions of students reported improvements or no change in financial stress, mood, anxiety, and RNT. Limitations: Students from one university particiapted in this cross-sectional survey. Conclusions: This study adds to the understanding of how higher education students are experiencing stress and are coping with the uncertainties of the COVID-19 pandemic in Ghana.

The recent years have witnessed a fast-paced development of perovskite solar cells (PSCs). Unfortunately, the vast majority of PSCs relies on the use of highly polar aprotic solvents during the preparation process, such as dimethylformamide (DMF), which is toxic and detrimental to both humans and the environment. Here, we describe the preparation of PSCs under ambient conditions from an aqueous solution of lead nitrate, to which polyvinylpyrrolidone (PVP) was added in order to enhance the photoelectric performance of the PSCs. By a combination of SEM, EIS, PL and UV spectroscopy and other characterization approaches, we show that the PVP additive is effective in inhibiting carrier recombination, enhancing composite resistance and reducing film defects. Ultimately, we achieved an outstanding photoelectric performance of the PVP-doped PSCs shown by a power conversion efficiency (PCE) of 15.19% and an average steady-state PCE of 14.55% under AM 1.5G simulated solar irradiation with a shadow mask of 0.1 cm2. The PCE continued to be over 80% of the initial PCE after 60 days of storage. FInally, the introduced PVP-doped PSCs present a low-cost and low-toxicity way to commercialize perovskite solar cells.

Aiming at the dynamic characteristics test bench of sliding bearings, the dynamic model is established. Based on the forward and inverse dynamic problems of the bearing, a simulation evaluation method for the identification accuracy of the sliding bearing dynamic characteristics is proposed and the algorithm is verified. The identification errors of dynamic characteristic coefficients under different excitation frequencies are analyzed, the sensitivities of single frequency excitation method and dual-frequency excitation method to test error are contrastively analyzed, and the influence laws of dynamic characteristic identification accuracy of sliding bearing are evaluated. Based on which the traditional single frequency excitation method has been improved. The dynamic characteristic test should be carried out respectively in the low frequency range and the high frequency range. The main stiffness and cross damping are the average of two tests, the main damping is the identification value in the high frequency, and the cross stiffness is the identification value in the low frequency. That will effectively reduce the impact of test error. The obtained data and laws could support the improvement of the dynamic characteristics test method of sliding bearings and the confirmation of test parameters, thereby the accuracy of dynamic characteristics identification is improved.

Mitochondria can fuse or divide, a phenomenon known as mitochondrial dynamics, and their distribution within a cell changes according to the physiological status of the cell. However, the functions of mitochondrial dynamics during spermatogenesis in animals other than mammals and fruit flies are poorly understood. In this study, we analyzed mitochondrial distribution and morphology during spermiogenesis in Sipuncula (Phascolosoma esculenta) and investigated the expression dynamics of mitochondrial fusion-related protein MFN2 and fission-related protein DRP1 during spermiogenesis. The mitochondria, which were elliptic with abundant lamellar cristae, were mainly localized near the nucleus and distributed unilaterally in cells during most stages of spermiogenesis. Their major axis length, average diameter, cross-sectional area, and volume are significantly changed during spermiogenesis. mfn2 and drp1 mRNA and proteins were most highly expressed in coelomic fluid, a spermatid development site for male P. esculenta, and highly expressed in the breeding stage compared to in the non-breeding stage. MFN2 and DRP1 expression levels were higher in components with many spermatids than in spermatid-free components. Immunofluorescence revealed that MFN2 and DRP1 were consistently expressed and that MFN2 co-localizes with mitochondria during spermiogenesis. The results provide evidence for an important role of mitochondrial dynamics during spermiogenesis from morphology and molecular biology in P. esculenta, broadening insights into the role of mitochondrial dynamics in animal spermiogenesis.

Background: Neurofilament light chain (NfL) and glial fibrilliary acidic protein (GFAP) have been suggested to be biomarkers of the pathophysiological process of neuromyelitis optica spectrum disorders (NMOSD), but the relationship between the plasma levels of these molecules with disease activity and treatment is incompletely understood. Objective: To investigate the treatment effects of disease-modifying drugs on plasma neurofilament light chain (pNfL) and plasma glial fibrillary acidic protein (pGFAP) and explore the predictive value of pNfL and pGFAP in the activity of NMOSD. Methods: pNfL and pGFAP levels were measured using single-molecule arrays in 72 patients with NMOSD and 38 healthy controls (HCs). Patients with NMOSD received tocilizumab ( n = 29), rituximab ( n = 23), oral prednisone ( n = 16), and oral azathioprine or mycophenolate mofetil ( n = 4). Results: NMOSD patients had significantly higher pNfL and pGFAP levels than HCs (pNfL, 18.3 (11.2–39.3) versus 11.5 (7.0–23.3) pg/mL; p = 0.001; pGFAP, 149.7 (88.6–406.5) versus 68.7 (59.4–80.8) pg/mL; p

BackgroundInterleukin-6 receptor blockade is effective in reducing the risk of relapses in neuromyelitis optica spectrum disorder (NMOSD). However, its efficacy during acute attacks of NMOSD remains elusive.ObjectiveWe investigated the effects of tocilizumab on disability during acute attacks, as well as its maintenance, in patients with moderate-to-severe myelitis.MethodsNineteen patients with NMOSD received tocilizumab treatment as add-on to high-dose methylprednisolone (HDMP) in acute myelitis and twenty-two patients who only received HDMP were compared. Disease disability was assessed using a multi-level scaling system that included the expanded disability status scale (EDSS), Hauser ambulation index (HAI), modified Rankin scale (mRS), pain numerical rating scale (NRS), functional assessment of chronic illness therapy-fatigue scale (FACIT-F), activity of daily living (ADL), EuroQol five-dimensions-three-level questionnaire (EQ-5D-3L), and sensory function score and bowel and bladder function score in Kurtzke functional systems scores (FSS).ResultsImproved EDSS, HAI, and mRS, as well as increased ADL and EQ-5D-3L were significant in patients on tocilizumab compared with those on steroids as monotherapy at 3 months (p < 0.05). Both groups of patients showed improved pain, fatigue, sensory function, and autonomic function at follow-ups, compared with baseline respectively. The changes in NRS, FACIT-F, and sensory and autonomic FSS showed no significant differences between the two groups. Tocilizumab significantly lowered the risk of relapses (HR = 0.21, 95% CI 0.06–0.76, p = 0.017) and reduced the annualized relapse rate compared with those by steroids (0.1 ± 0.2 vs 0.5 ± 0.6, p = 0.013).ConclusionEarly initiation of tocilizumab provided a safe and effective add-on alternative during attacks, and its maintenance contributed to a significant reduction of relapse rate in NMOSD.

Phascolosoma esculenta, an economically important species inhabiting the high tide areas of the intertidal zone, is particularly sensitive to water pollution. Considering its potential as a bioindicator, studies on the ecotoxicology of P. esculenta are imperative. The toxic effects of cadmium (Cd) were analyzed by exposing P. esculenta to different concentrations of Cd (6, 24, 96 mg/L). In this study, the changes in the antioxidative indexes of total superoxide dismutase (T-SOD), glutathione s-transferase (GST), reduced glutathione (GSH), and microscale malondialdehyde (MDA) were recorded. Copper/zinc superoxide dismutase (Cu/Zn SOD) is one of the most important free radical scavenging members. To reveal the antioxidative function of P. esculenta, an important member of the antioxidative system, designated Pe-Cu/Zn SOD, was cloned and analyzed. Phylogenic analysis revealed that Pe-Cu/Zn SOD was located in the invertebrate evolutionary branch of intracellular Cu/Zn SOD (icCu/Zn SOD). The quantitative real-time polymerase chain reaction results showed that Pe-Cu/Zn SOD messenger ribonucleic acid was widely expressed in all tissues examined. The highest expression levels in coelomic fluid after Cd exposure indicated its function in the stress response. Using a prokaryotic expression system, we obtained a Pe-Cu/Zn SOD recombinant protein, which enhanced the heavy metal tolerance of Escherichia coli. In vivo assays also confirmed that the Pe-Cu/Zn SOD recombinant protein had an antioxidative and free radical scavenging ability. A Cd toxicity experiment, in which purified Pe-Cu/Zn SOD protein was injected into the body cavities of P. esculenta, showed that the reactive oxygen species content in the coelomic fluid of the experimental group was significantly lower compared with the control group. These results suggest that Pe-Cu/Zn SOD played a role in Cd detoxification by chelating heavy metal ions and scavenging reactive oxygen free radicals, and that P. esculenta could be used as a bioindicator to evaluate heavy metal pollution.

We thank Kuo et al. for their comments [...]

Background: Progressive retinal neuroaxonal damage after acute optic neuritis may occur in neuromyelitis optica spectrum disorder (NMOSD). However, it is unclear if treatments used to prevent attacks influence neurodegeneration.Objectives: We aimed to investigate retinal damage in patients treated with disease-modifying drugs in a longitudinal study.Methods: We retrospectively included 50 patients with aquaporin 4-antibody-seropositive NMOSD. Peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell complex (mGCC) thickness, total macular volume (TMV), and optic disc measures were acquired by spectral domain optical coherence tomography in patients treated with tocilizumab, rituximab, and azathioprine.Results: Longitudinally, in eyes with a history of ON (NMOSDON+), we observed annual thinning of mGCC [tocilizumab: −1.77 (−3.44, −0.09) μm, p = 0.041; rituximab: −2.03 (−3.58, −0.48) μm, p = 0.017; azathioprine: −1.79 (−2.22, −1.37) μm, p < 0.001], and pRNFL [tocilizumab: −2.07 (−0.75, −3.39) μm, p = 0.005; rituximab: −2.18 (−0.36, −4.00) μm, p = 0.023; azathioprine: −2.37 (−0.98, −3.75) μm, p = 0.003], reduced TMV [tocilizumab: −0.12 (−0.22, −0.01) mm3, p = 0.028; rituximab: −0.15 (−0.21, −0.08) mm3, p = 0.001; azathioprine: −0.12 (−0.20, −0.04) mm3, p = 0.006], and increased cup area [tocilizumab: 0.08 (−0.01, 0.16) mm2, p = 0.010; rituximab: 0.07 (0.01, 0.12) mm2, p = 0.019; azathioprine: 0.14 (0.02, 0.26) mm2, p = 0.023]. However, we detected no significant differences in annual changes in mGCC, pRNFL, TMV, and cup area between patients with tocilizumab, rituximab, and azathioprine in NMOSDON+ eyes. NMOSDON− eyes did not display mGCC or pRNFL thinning in patients treated with tocilizumab and rituximab. Intriguingly, we observed significant thinning of mGCC in patients treated with azathioprine compared with tocilizumab [−0.84 (−1.50, −0.18) μm vs. −0.19 (−0.87, 0.48) μm, p = 0.012] and rituximab [−0.84 (−1.50, −0.18) μm vs. −0.07 (−1.25, −2.51) μm, p = 0.015] in NMOSDON− eyes.Conclusions: This study demonstrated that retinal ganglion cell loss is independent of ON attacks in NMOSD. Tocilizumab and rituximab may delay mGCC thinning in NMOSDON− eyes compared with azathioprine.

Tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, showed its therapeutic efficacy on neuromyelitis optica spectrum disorder (NMOSD). To assess the immunological effects of this drug on B cells, follicular T helper (Tfh) cells, and peripheral T helper (Tph) cells in patients with NMOSD, peripheral B cell and Tfh cell phenotypes were evaluated in 26 patients with NMOSD before and after tocilizumab treatment by nine-color flow cytometry, as well as the expression of costimulatory and co-inhibitory molecules on B cells. Results showed that the frequency of CD27+IgD− switched memory B cells, CD27-IgD- double-negative B cells, and CD27highCD38high antibody-secreting cells was increased in patients with NMOSD. Tocilizumab treatment led to a significant shift of B cells to naïve B cells from memory B cells after 3 months. Three markers on B cells associated with T-cell activation (i.e., CD86 CD69, and HLA-DR) were downregulated after tocilizumab treatment. The frequencies of total Tfh and Tph cells were decreased, whereas that of follicular regulatory T cells tended to increase. Intrinsic increased PD-L1 and PD-L2 expression was characteristic of B cells in patients with NMOSD. Tocilizumab selectively restored PD-L1 on B-cell subsets. These results provided evidence that tocilizumab enhanced B- and T-cell homoeostasis by regulating B-cell differentiation and inhibiting lymphocyte activation in patients with NMOSD.

Objective: The purpose of this study was to discover the population structure and genetic diversity of Inner Mongolia White Cashmere goats (IMCGs) and demonstrate the effect of inbreeding on the live body weight (LBW), cashmere yield (CY), fiber length (FL), and fiber diameter (FD) of IMCGs.Materials and Methods: All data were collected from pedigree information and production performance records of IMCGs from 1983 to 2019. The population structure and genetic diversity were analyzed by Endog 4.8 software. Inbreeding coefficients were obtained by the pedigree package in R. Then, a linear regression model was used to analyze how inbreeding influences economic traits in IMCGs. Four levels of inbreeding coefficients (Fi) were classified in this study, including Fi = 0, 0< Fi ≤ 6.25, 6.25< Fi ≤ 12.5 and Fi≥12.5. Variance analysis was performed to determine whether inbreeding levels had a significant effect on economic traits in IMCGs.Results: The proportions of rams and dams in IMCGs for breeding were relatively small, with values of 0.8 and 20.5%, respectively. The proportion of inbred animals in the entire population was high, with values up to 68.6%; however, the average inbreeding coefficient and relatedness coefficient were 4.50 and 8.48%, respectively. To date, the population has experienced 12 generations. The average generation interval obtained in the present study was 4.11 ± 0.01 years. The ram-to-son pathway was lowest (3.97 years), and the ewe-to-daughter pathway was highest (4.24 years). It was discovered that the LBW, CY, and FL increased by 3.88 kg, 208.7 g, and 1.151 cm, respectively, with every 1% increase in the inbreeding coefficient, and the FD decreased by 0.819 μm with every 1% increase in the inbreeding coefficient. Additionally, multiple comparison analysis indicated that when the inbreeding coefficient was higher than 6.25%, the LBW showed an obvious decreasing trend. The threshold value of inbreeding depression in the CY is 12.5%. However, inbreeding depression has not been observed in the FL and FD.Conclusion: Pedigree completeness needs to be further strengthened. The degree of inbreeding in this flock should be properly controlled when designing breeding programs.

Abstract Background Synergistic therapy of tumor is a promising way in curing cancer and in order to achieve effective tumor therapy with real-time drug release monitoring, dynamic cellular imaging and antitumor activity. Results In this work, a polymeric nanoparticle with Forster resonance energy transfer (FRET) effect and chemo-photodynamic properties was fabricated as the drug vehicle. An amphiphilic polymer of cyclo(RGDfCSH) (cRGD)-poly(ethylene glycol) (PEG)-Poly(l-histidine) (PH)-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por)-acting as both a photosensitizer for photodynamic therapy (PDT) and absorption of acceptor in FRET was synthesized and self-assembled into polymeric nanoparticles with epirubicin (EPI)-acting as an antitumor drug for chemotherapy and fluorescence of donor in FRET. Spherical EPI-loaded nanoparticles with the average size of 150 ± 2.4 nm was procured with negatively charged surface, pH sensitivity and high drug loading content (14.9 ± 1.5%). The cellular uptake of EPI-loaded cRGD-PEG-PH-PCL-Por was monitored in real time by the FRET effect between EPI and cRGD-PEG-PH-PCL-Por. The polymeric nanoparticles combined PDT and chemotherapy showed significant anticancer activity both in vitro (IC50 = 0.47 μg/mL) and better therapeutic efficacy than that of free EPI in vivo. Conclusions This work provided a versatile strategy to fabricate nanoassemblies for intracellular tracking of drug release and synergistic chemo-photodynamic therapy.

Abstract Phenotypic and functional heterogeneity is one of the hallmarks of human cancers. Tumor genotype variations among tumors within different patients are known as interpatient heterogeneity, and variability among multiple tumors of the same type arising in the same patient is referred to as intra-patient heterogeneity. Subpopulations of cancer cells with distinct phenotypic and molecular features within a tumor are called intratumor heterogeneity (ITH). Since Nowell proposed the clonal evolution of tumor cell populations in 1976, tumor heterogeneity, especially ITH, was actively studied. Research has focused on the genetic basis of cancer, particularly mutational activation of oncogenes or inactivation of tumor-suppressor genes (TSGs). The phenomenon of ITH is commonly explained by Darwinian-like clonal evolution of a single tumor. Despite the monoclonal origin of most cancers, new clones arise during tumor progression due to the continuous acquisition of mutations. It is clear that disruption of the "epigenetic machinery" plays an important role in cancer development. Aberrant epigenetic changes occur more frequently than gene mutations in human cancers. The epigenome is at the intersection of the environment and genome. Epigenetic dysregulation occurs in the earliest stage of cancer. The current trend of epigenetic therapy is to use epigenetic drugs to reverse and/or delay future resistance to cancer therapies. A majority of cancer therapies fail to achieve durable responses, which is often attributed to ITH. Epigenetic therapy may reverse drug resistance in heterogeneous cancer. Complete understanding of genetic and epigenetic heterogeneity may assist in designing combinations of targeted therapies based on molecular information extracted from individual tumors.

Previous studies have shown that cashmere production (CP) is related to fibre length (FL), mean fibre diameter (MFD) and live body weight (LWT) in Inner Mongolia cashmere goats (IMCGs). However, the correlation magnitudes of these relationships have not been determined to date. The production year, herd, age, birth status, sex, cashmere production, fibre grades, fibre length, mean fibre diameter and live body weight were obtained for IMCGs from yearlings to 5-year-olds. A multilevel mixed model was constructed to discern the impact factors affecting CP. It was concluded that the production year, herd, age, sex, FL, MFD and LWT had highly significant effects on CP (p .05). The restricted maximum likelihood method (REML) was used to estimate the relationship of CP to all impact factors. Positive correlations were observed between CP and other important economic traits. The regression coefficients for FL, MFD and LBW were 26.50 g/cm, 31.67 g/µm and 2.26 g/kg, respectively. The model fit is relatively good, and the adjusted R-squared value is 0.43. Using a similar method, the relationship of CP to these impacting factors within each fleece grade was analysed. The results showed that LWT had no significant effect on CP in superfine and coarse cashmere grades. Additionally, MFD was not related to CP in coarse cashmere. However, FL, MFD and LWB had highly significant effects on CP in all other FD grades. The regression coefficients of cashmere production for other economic traits varied based on fleece grade.Highlights Cashmere production was positively correlated with live body weight for Inner Mongolia Cashmere goats (IMCGs), which can facilitate indirect selection and reduce the cost of measurement. The fibre diameter should be considered to maintain good quality by establishing a nucleus herd, thereby increasing economic income and protecting a variety of resources.

Spermatogenesis is the intricate and coordinated process by which spermatogonia develop into haploid differentiated spermatozoa. Mitochondria are essential for spermatogenesis, and prohibitin (PHB) is closely associated with mitochondrial structure and function during spermatogenesis. Although PHB has been implicated in spermatogenesis in some taxa, its roles in Opsariichthys bidens have not been determined. In this study, the expression patterns and potential functions of PHB in spermatogenesis in O. bidens were characterized using histological microscopic observations, PCR cloning, real-time quantitative PCR (qPCR), Western blotting (WB) and immunofluorescence (IF). The full-length cDNA of Ob-phb was 1500 bp encoding 271 amino acids. A sequence alignment demonstrated that the PHB protein is conserved among different animals. qPCR revealed that phb mRNA is widely distributed in O. bidens and highly expressed in the testes at stages IV and V. WB revealed that Ob-PHB is located in the mitochondria of testes. IF revealed the colocalization of PHB signals and mitochondria. Signals were detected around nuclei in spermatogonia and spermatocytes, gradually moving to the tail region during spermiogenesis, and finally aggregating in the midpiece. These results indicate that Ob-PHB was expressed in the mitochondria during spermatogenesis. In addition, this study proposed Ob-PHB may participate in the degradation of mitochondria and cell differentiation during spermatogenesis.

Snowmelt water in spring is an important source of soil water, which is critical to supporting crop growth. Quantifying the contribution of snowmelt water to soil water and its dynamic changes is essential for evaluating soil moisture and allocating agricultural water resources. In this paper, through controlled outdoor experiments, different snow depths and soil depth gradients were set; and snow, precipitation, and soil samples were collected regularly. To analyze the contribution of snowmelt water to soil water and its dynamic changes, the MAT-253 stable isotope ratio mass spectrometer was adopted for hydrogen and oxygen isotope analyses. The results showed that the snowmelt water for snow depths of 10 cm, 30 cm, and 50 cm all contributed to the 0–30 cm soil layer. The contribution increased with soil depth, contributing 8.13%, 8.55%, and 11.24%, respectively. The contribution of the snow cover at the same depth to the soil moisture at different depths also varied, i.e., the contribution increased with increasing soil depth. The snowmelt water retention time at depths of 10 cm, 30 cm, and 50 cm was inconsistent, i.e., it was the longest at 0–10 cm (average of 69 days), followed by 20–30 cm (average of 59 days), and the shortest at 10–20 cm (average of 54 days). The greater the snow depth, the shorter the retention time of the snowmelt water in the different soil layers. For surface soil, the contribution of the snowmelt water at greater depths was significantly different; while for deep soil, the contribution was more sensitive to the snow depth. Regardless of snow depth, soil contributions at different depths were significantly different. Precipitation also affected the contribution of the snowmelt water to the soil water, exhibiting different effects at different depths.

Porcine epidemic diarrhea virus (PEDV) is one of the major enteric pathogens, causing severe enteric disease, resulting in enormous economic losses. The ORF3 gene encodes an accessory protein which is related to the infectivity and virulence of PEDV. In this study, 33 PEDV positive field samples were collected from Guangxi, from 2017 to 2019, and the genetic diversity of ORF3 was investigated. Thirty-eight strains of ORF3 were obtained, and these were composed of five strains of ORF3 named Guangxi naturally truncated strains that were 293 bp in length, with continuous deletions from 172 to 554 bp. The Guangxi naturally truncated strains encoded a truncated protein of 89 amino acids, which had clustered into a new group referred to as Group 3, and these might be involved in the variations of virulence. Three genotypes (G1-1 subgroup, G1-3 subgroup, and Group 3) existed simultaneously in Guangxi based on the genetic and evolutionary analysis of the ORF3 gene. The sequence information in the current study will hopefully facilitate the establishment of a diagnostic method that can differentiate the PEDV field stains. Continued surveillance will be useful for monitoring PEDV transmission. Differentiation of the ORF3 genes in PEDV field strains can help us to choose an appropriate PEDV vaccine candidate in the future and prevent outbreaks of PED more effectively.

For high-end CNC machine tools, the stiffness of the spindle system is one of the most important performance indicators. In this paper, the hydrostatic motorized spindle system of a grinding machine is taken as the research object, and a two-degree-of-freedom stiffness model of the spindle system considering rotor swing is proposed. The stiffness of the spindle system under different excitation frequencies is analyzed, and the contributions of the stiffness of two bearings to the stiffness of the spindle system are evaluated. The vibration test on the spindle system is implemented through the hammering method. The vibration responses of the spindle system are obtained, and the stiffness of the spindle system is identified. The results show that the test results of the stiffness of the spindle system are in good agreement with the theoretical calculation, with an average error of about 14.21%. The research in this paper can provide theoretical and data support for bearing design and stiffness evaluation of a hydrostatic spindle system.

Background: The prevalence of mental health concerns among university students in the United States (U.S.) continues to increase, while current treatments, including medication and counseling, present shortcomings. Higher dairy and calcium intakes are associated with protective effects on mental health; however, previous studies have focused on investigating singular relationships between dairy and calcium intakes and mental health measures. A more complex exploration of these relationships is warranted to better examine whether increasing dairy and calcium intakes could serve as an intervention to improve mental health. The present study sought to further characterize the relationships between dairy and calcium intake, perceived stress, and a variety of mental health measures using linear regression and moderation analyses. Methods: The present cross-sectional study involved students studying at three large U.S. universities, and data collection occurred from April to May 2020 when students were learning remotely due to the COVID-19 pandemic. An online survey comprising validated tools was distributed among students to assess dairy and calcium intake, perceived stress, anxiety, negative and positive moods, rumination, and resilience, sleep quality and duration, dietary risk, and physical activity. Results: A total of 1233 students completed the study. Higher dairy and calcium intake was coincident with lower perceived stress and higher positive mood scores, while higher calcium intake was also coincident with lower anxiety, rumination, and higher resilience scores. Additionally, as calcium intake increased, the relationship between perceived stress and anxiety and the relationship between perceived stress and negative mood weakened. Dairy intake did not have this effect. Conclusions: Based on the results, and considering that calcium is a shortfall nutrient, universities should consider initiating programs and public health campaigns to promote dairy and calcium intake among this population.

Background: Obesity is a growing epidemic among university students, and the high levels of stress reported by this population could contribute to this issue. Singular relationships between perceived stress; engagement in restrained, uncontrolled, and emotional eating; sleep; dietary risk; and body mass index (BMI) have been reported in the current body of literature; however, these constructs interact with each other, and the complex relationships among them are infrequently examined. Therefore, the aim of the present study was to explore the complex relationships between these constructs using mediation and moderation analyses stratified by gender. Methods: A cross-sectional study, enrolling university students from the United States (U.S.), the Netherlands, South Korea, Malaysia, Ireland, Ghana, and China, was conducted between October 2020 and January 2021 during the COVID-19 pandemic. Perceived stress; maladaptive eating behaviors including restrained, uncontrolled, and emotional eating; sleep duration and quality; dietary risk; and BMI were assessed using validated questionnaires, which were distributed through an online platform. Results: A total of 1392 students completed the online survey (379 male, 973 female, and 40 who self-identified as “other”). Uncontrolled and emotional eating mediated the relationship between perceived stress and dietary risk for both males and females; higher sleep quality weakened this relationship among female students but not males. Emotional eating mediated the relationship between perceived stress and BMI for both males and females, but higher sleep quality weakened this relationship only among females. Conclusions: Our findings suggest that students in higher education are likely to benefit from interventions to reduce uncontrolled and emotional eating. Programs that improve sleep quality, especially during highly stressful periods, may be helpful.