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The lower atmosphere forcing plays an important role in forming the sporadic E (Es) layer in the ionosphere. In this study, a comparative study of the Es layer recorded by ionosondes at the middle latitude regions was carried out between the plateau and plain regions in China. The two ionosonde stations (Zhangye, 39.21°N, 100.54°E and Beijing, 40.25°N, 116.25°E) are located at the Qinghai–Tibet Plateau and North China Plain, respectively. The data during the year 2018 were used to reveal the characteristics of the Es layer. The occurrence probability, the critical frequency (foEs) and the base virtual height (h’Es) were considered in this study. Results show that: (1) The diurnal and seasonal variations of the occurrence probability between these two regions are similar. The maximum occurrence probability is at noontime and in the summer season. However, the Es at Zhangye occurred more frequently than Beijing at nighttime and in winter to early spring. (2) Similar to previous studies, the maximum value of foEs at Beijing mainly occurred in summer. Interestingly, the maximum value is in winter at Zhangye station. (3) The characteristics of the anomaly of the Es layer at Zhangye are mostly consistent with the characteristics of atmospheric gravity waves in the Qinghai–Tibet Plateau. Therefore, compared with observations at Beijing, the anomalies of the Es layer at Zhangye (at night and in winter to spring) might be attributed to gravity waves in the lower atmosphere over the Qinghai–Tibet Plateau.

Abstract Background Deregulated inflammation and immune deficit both intricately associate with cancer initiation and progression, which have been increasingly exploited as prognostic biomarkers and therapeutic targets. Recently, systemic immune-inflammation index (SII) based on peripheral neutrophil, lymphocyte and platelet counts serves as a novel and powerful cancer biomarker with prognostic significance in multiple types of malignancies. Here, we sought to evaluate the prognostic value of preoperative SII in patients with primary oral squamous cell carcinoma (OSCC) after curative resection. Methods Two independent cohorts with a total number of 309 patients with OSCC from two tertiary referral hospitals were included and defined as training (Nanjing, 138) and validation (Wuxi, 171) cohort, respectively. Preoperative SII in both cohorts was calculated and its optimal cutoff value was initially determined by X-tile software in the training cohort and then verified in the validation cohort. Results Our data indicated that high SII (≥ 484.5) was significantly associated with larger tumor size (P

Abstract We report the first case of a 12‐year‐old boy with Wiskott‐Aldrich syndrome who developed CD20‐weakly expressed and CD30‐highly expressed Epstein‐Barr virus–related post‐transplant lymphoproliferative disorder refractory to rituximab treatment. The patient was effectively and safely treated with personalized low‐dose chemotherapy and subsequently remained in complete remission for 1 year.

For cosmetic and reconstructive purposes in the setting of small-volume adipose tissue damage due to aging, traumatic defects, oncological resections, and degenerative diseases, the current strategies for soft tissue replacement involve autologous fat grafts and tissue fillers with synthetic, bioactive, or tissue-engineered materials. However, they all have drawbacks such as volume shrinkage and foreign-body responses. Aiming to regenerate bioactive vascularized adipose tissue on biomaterial scaffolds, adipose tissue engineering (ATE) has emerged as a suitable substitute for soft tissue repair. The essential components of ATE include scaffolds as support, cells as raw materials for fat formation, and a tolerant local environment to allow regeneration to occur. The commonly loaded seeding cells are adipose-derived stem cells (ASCs), which are expected to induce stable and predictable adipose tissue formation. However, defects in stem cell enrichment, such as donor-site sacrifice, limit their wide application. As a promising alternative approach, cell-free bioactive scaffolds recruit endogenous cells for adipogenesis. In biomaterials without cell seeds, the key to sufficient adipogenesis relies on the recruitment of endogenous host cells and continuous induction of cell homing to scaffolds. Regeneration, rather than repair, is the fundamental dominance of an optimal mature product. To induce in situ adipogenesis, many researchers have focused on the mechanical and biochemical properties of scaffolds. In addition, efforts to regulate an angiogenic and adipogenic microenvironment in cell-free settings involve integrating growth factors or extracellular matrix (ECM) proteins onto bioactive scaffolds. Despite the theoretical feasibility and encouraging results in animal models, few of the reported cell-free biomaterials have been tested in humans, and failures of decellularized adipose tissues in adipogenesis have also been reported. In these cases, the most likely reason was the lack of supporting vasculature. This review summarizes the current status of biomaterials without cell seeds. Related mechanisms and influencing factors of in situ adipogenesis in cell-free biomaterials, dilemma in the development of biomaterials, and future perspectives are also addressed.

Prenatal mortality remains a significant concern to the pig farming industry around the world. Spontaneous fetal loss ranging from 20 to 45% by term occur after fertilization, with most of the loss happening during the implantation period. Since the factors regulating the high mortality rates of early conceptus during implantation phases are poorly understood, we sought to analyze the overall gene expression changes during this period, and identify the molecular mechanisms involved in conceptus development. This work employed Illumina’s next-generation sequencing (RNA-Seq) and quantitative real-time PCR to analyze differentially expressed genes (DEGs). Soft clustering was subsequently used for the cluster analysis of gene expression. We identified 8236 DEGs in porcine conceptus at day 9, 12, and 15 of pregnancy. Annotation analysis of these genes revealed rRNA processing (GO:0006364), cell adhesion (GO:1904874), and heart development (GO:0007507), as the most significantly enriched biological processes at day 9, 12, and 15 of pregnancy, respectively. In addition, we found various genes, such as T-complex 1, RuvB-like AAA ATPase 2, connective tissue growth factor, integrins, interferon gamma, SLA-1, chemokine ligand 9, PAG-2, transforming growth factor beta receptor 1, and Annexin A2, that play essential roles in conceptus morphological development and implantation in pigs. Furthermore, we investigated the function of PAG-2 in vitro and found that PAG-2 can inhibit trophoblast cell proliferation and migration. Our analysis provides a valuable resource for understanding the mechanisms of conceptus development and implantation in pigs.

Objective. To evaluate the impacts of different metastatic patterns on the prognosis of patients with invasive intraductal papillary mucinous neoplasm (IPMN). Materials and Methods. All patients who were diagnosed with invasive IPMN in the Surveillance, Epidemiology, and End Results SEER database (2010–2015) were included in this study. They were grouped according to different metastatic patterns. Kaplan–Meier analysis and log-rank test were used for the comparison of their survival rates. The hazard ratio (HR) with 95% confidence interval (CI) was analyzed using the Cox proportional-hazards model. Results. A total of 2264 cases were included in this study. The most common metastatic site was the liver. The patients with the nonorgan metastasis demonstrated the best survival outcomes, while those with multiple metastases showed the worst survival outcomes. As compared to the patients with isolated liver metastasis, those with isolated lung and other organ metastases showed better overall survival rates and tumor-specific survival rates. The patients with liver, lung, multiple, and other organ metastases or of age >60 years were the independent predictors of poor prognosis. Conclusions. The patients with isolated lung and other organ metastases demonstrated better survival outcomes as compared to those with isolated liver metastasis. The patients with nonorgan metastasis demonstrated the best survival outcomes, while those with multiple metastases showed the worst survival outcomes. Further studies are needed to determine a highly selected subset of patients, who might benefit from surgery or chemotherapy.

The earthquakes could induce ionospheric electron density disturbance at D/E, F layer and even topside of ionosphere. Subsequently the ionospheric disturbance would change the electromagnetic field from the ground based VLF transmitter. Nowadays, the electromagnetic field recorded by Low earth orbit (LEO) satellite have been used to study the possible seismic anomalies frequently. It is essential to study systematically how the ionospheric disturbance influences the electromagnetic field at the altitude of LEO satellite theoretically. In this paper, we construct a full wave model to simulate the influence of the amplitude, altitude, and scale of the ionospheric disturbance on the electromagnetic field in the ionosphere from the ground based VLF transmitter. The result shows the electromagnetic field at the altitude of satellite changes obviously when the wave encounters an ionospheric disturbance in the D/E layer. The variation of the electromagnetic field increases with the amplitude and scale of the ionospheric disturbance. However, the influence of the ionospheric disturbance in the F layer just has a local effect on the electromagnetic field. The influence of ionospheric disturbance in the nighttime on the variation of electromagnetic field is smaller compared with it in the daytime. These conclusions can improve our understanding of using electromagnetic field observed by satellite to study seismic anomalies.

The sporadic E (Es) layer is a thin layer of ion plasma enhancement in the E-region ionosphere, typically at altitudes of 90–120 km with vertical and horizontal extent of several or several tens of kilometers. As the transition region between the lower and upper atmosphere, this layer is of critical importance for ionospheric studies. The most economical but effective method to observe this layer is using ionosonde, which, however, is incapable of capturing the finer structure or the internal inhomogeneity of the Es layer as the range resolution is on the order of kilometers. To overcome this limitation, we employ the frequency domain interferometry (FDI) technique, a technique that has been successfully applied to the analysis of some radar and sonar measurements. Here, we use the Es layer measurements near Wuhan, China (114°22′E, 30°30′N) on 8 June 2021 as examples to showcase the capability of this technique. Our results show that the spatial resolution of ionosonde imaging is remarkably increased: the complexity of the internal fine structure in the Es layer can be well observed in the FDI-processed ionograms, whereas the intrinsic range resolution is several kilometers. Moreover, by comparing the ionograms obtained with and without the FDI technique, it is found that the FDI-processed ionogram is particularly suitable for the observation of evolutional processes in the Es layer, as well as the identification of different types of Es layer. With this level of spatial resolution, ionosonde, in combination with the FDI technique, opens the possibility for more refined observations of the Es layer.

Background: The management of type II endoleaks (T2ELs) remains controversial in current literature. Hence, this study aimed to explore the natural history of isolated type II endoleak after endovascular aneurysm repair (EVAR) and its influence on long-term outcomes based on a 10-year follow-up at a tertiary medical center. Methods: From January 2011 to April 2021, consecutive patients who underwent elective EVAR were reviewed. The demographics, clinical characteristics, treatment details, imaging information, in the event of T2ELs, and outcomes were extracted. Results: A total of 287 patients were included for analysis. Isolated T2EL was identified in 79 patients (27.5%), while no endoleak was found in 208 patients (72.5%). The mean age at EVAR was 68.1 ± 8.9 years (range, 41–92 years) and the majority of patients were male (81.5%). The mean follow-up duration was 42.7 months (range, 2–119.7 months). Among the 79 patients with isolated T2ELs, 33 (41.8%, 33/79) were early and 46 (58.2%, 46/79) were late. Spontaneous resolution of T2ELs was identified in 29 patients (36.7%, 29/79). Persistent T2ELs were observed in 50 patients (63.3%, 50/79). No sac growth was seen in 33 patients (66%, 33/50) and these patients were managed conservatively. The remaining 17 patients (34%, 17/50) showed significant sac growth. Six of them declined intervention due to various reasons and the remaining 11 patients underwent interventional embolization for T2ELs. Following the embolization, 2 patients had complete resolution of T2ELs and 9 patients had persistent T2ELs. Among the patients with persistent T2ELs, 2 patients (2/9) still showed progressive sac growth, and one of them died from aneurysm rupture; the remaining 7 patients (7/9) showed no sac growth. Patients with isolated T2ELs had a higher incidence of sac growth than patients without any endoleak (21.5% vs 4.3%, p < 0.001), while no difference was found in overall survival between the two groups. In Cox regression analysis, only higher age was independently associated with worse survival. Conclusions: Type II Endoleak was significantly associated with aneurysm sac growth and no association with survival was observed.

Extracellular vesicles (EVs) regulate multiple physiological processes. Seminal plasma contains numerous EVs that may deliver functional molecules such as small RNAs (sRNAs) to the sperm. However, the RNA profiles in the boar seminal plasma extracellular vesicles (SP-EVs) and its function have not been characterized. The aim of this study was to characterize the functions and sRNA profiles in the boar SP-EVs using deep sequencing technology. Briefly, boar SP-EVs were isolated by differential ultracentrifugation and confirmed with a transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), and Western blot. The isolated boar SP-EVs contained numerous and diverse sRNA families, including microRNAs (miRNAs, 9.45% of the total reads), PIWI-interacting RNAs (piRNAs, 15.25% of the total reads), messenger RNA fragments (mRNA, 25.30% of the total reads), and tRNA-derived small RNAs (tsRNA, 0.01% of the total reads). A total of 288 known miRNAs, 37 novel miRNA, and 19,749 piRNAs were identified in boar SP-EVs. The identified ssc-miR-21-5p may confer negative effects on sperm fertility based on a dual-luciferase reporter experiment. This study therefore provides an effective method to isolate SP-EVs and characterizes the sRNA profile.

Reproduction in goat is highly impeded by implantation failure. Of concern, the underlying mechanism leading to embryo implantation remains unclear. In this study, deep sequencing was employed through strand-specific Ribo-Zero RNA-Seq to characterize transcriptome changes in the endometrium during the maternal recognition of pregnancy. A total of 996 differential transcripts (115 lncRNAs and 881 mRNAs) existing between the pregnant and non-pregnant endometrium were revealed through bioinformatics analysis. The screening was performed on lncRNAs (XR_001918173.1, LNC_002760, and LNC_000599) and LNC_009053, to determine their potential role in regulating the synthesis of retinol and endometrium remolding through the proteasome pathway, respectively. The hypothesis of whether certain lncRNAs, namely, LNC_007223, LNC_005256, and LNC_010092 could play important roles in embryo implantation was tested. These novel findings are of paramount relevance to further elucidate the molecular mechanisms of embryo implantation and uncover new targets to improve goat reproduction.

Early pregnancy diagnosis in sows can significantly improve the efficiency of pig industry. Exosomes are membrane-covered nanovesicles that can transport microRNAs (miRNAs) and other molecular signals between cells. In other species, serum exosome-derived miRNAs can serve as good biomarkers of diseases and different physiological states, including pregnancy status. We hypothesized that circulating exosome-derived miRNAs might be used to differentiate the pregnancy status as early as several days after insemination in pigs. To test this hypothesis, we randomly assigned pigs for artificial insemination with fertile or dead semen (control group). Serum samples were obtained from pregnant pigs on days 9, 12, and 15 after insemination and from non-pregnant pigs on days 0, 9, 12, and 15 after insemination. Exosomes were isolated for RNA extraction. The exosomal RNA samples from pigs on day 9 of the estrus cycle and pregnancy were used for small-RNA sequencing. A total 321 miRNAs were identified in all samples. Twenty eight differentially abundant miRNAs were identified between the pregnant and control groups. miRNAs with | log2 (fold change)| > 2 from sequencing results were selected for validation by quantitative reverse-transcription-polymerase chain reaction (RT-qPCR) in larger samples. Finally two upregulated miRNAs (miR-92b-3p and miR-17-5p) in the pregnant groups (on days 9, 12, and 15 of pregnancy) were confirmed by RT-qPCR. In summary, we have successfully identified circulating exosomal miRNA profiles in the serum of pigs in early pregnancy. miR-92b-3p and miR-17-5p could be used as potential circulating biomarkers for early pregnancy diagnosis.

Implantable optical sensing devices that can continuously monitor physiological temperature changes hold great potential toward applications in healthcare and medical field. Here, we present a conceptual foundation for the design of biocompatible temperature sensing device by integrating renal clearable luminescent gold nanoparticles (AuNPs) with silk film (AuNPs-SF). We found that the AuNPs display strong temperature dependence in both near-IR fluorescence intensity and lifetime over a large temperature range (10–60°C), with a fluorescence intensity sensitivity of 1.72%/°C and lifetime sensitivity of 0.09 μs/°C. When integrated, the AuNPs with biocompatible silk film are implanted in the dorsal region of mice. The fluorescence imaging of the AuNPs-SF in the body shows a linear relationship between the average fluorescence intensity and temperature. More importantly,

Gastric involvement by seminoma is extremely rare and all the reported cases were associated with bulky retroperitoneal disease or occurred late as part of advanced disease. We report a unique case of seminoma presenting as gastric mucosal metastasis. The diagnosis of this case was complicated by no residual testicular tumor or pelvic/retroperitoneal lymph nodes metastasis and no available specific serum markers. The histological morphology and immunostains allowed the correct diagnosis to be made in this case. This case highlights the rare manifestation of seminoma, which appears to be a primary tumor of an unusual site of germ cell tumor metastasis.

Abstract We investigate the propagation characteristics of low‐altitude hiss in the ionosphere by numerical simulation with a two‐dimensional full‐wave model. The simulation results demonstrate that linear mode conversion from whistler to H+ band electromagnetic ion cyclotron wave and polarization reversal occur simultaneously where wave frequency matches the H+−He+ crossover frequency. This mode conversion efficiency shows sensitive dependence on wave normal angle and plays a significant role in the propagation of whistler emission near the local proton gyro‐frequency in the ionosphere by redistributing the wave energy below and above the H+−He+ cutoff frequency, which can explain the low‐altitude hiss observed by the Freja and Detection of Electromagnetic Emissions Transmitted from Earthquake Regions satellites, respectively. The energy of whistler‐mode low‐altitude hiss emission can be transferred to reflected left‐hand polarized electromagnetic ion cyclotron through mode conversion and the efficiency reaches a maximum for intermediate incident wave normal angle (of 45°).

Summary: Hsp90 is a target for anti-cancer drug development. Both the conformational events tuned by ATP/ADP and co-chaperones and the chaperoning cycle timing are required for Hsp90's fully functional display. Interfering with either one of the conformational events or the cycle timing will down-regulate Hsp90's function. In this manuscript, non-covalent allosteric modulators (SOMCL-16-171 and SOMCL-16-175) targeting Hsp90α’s middle domain (Hsp90M) were developed for the first time. Multiple techniques were then applied to characterize the interactions between two active compounds and Hsp90α. Two loops and one α-helix (F349-N360, K443-E451, and D372-G387) in Hsp90M were identified responsible for the recognition of SOMCL-16-171 and SOMCL-16-175. Meanwhile, the binding of SOMCL-16-171 and SOMCL-16-175 to Hsp90M was demonstrated to allosterically modulate the structure and function of Hsp90α’s N-terminal domain. Finally, cellular assays were conducted to evaluate the cellular activity of SOMCL-16-175, and the results indicate that SOMCL-16-175 destabilizes Hsp90's client proteins and reduces cell viability. : Molecular Biology; Molecular Structure; Cancer Subject Areas: Molecular Biology, Molecular Structure, Cancer

Many therapeutic monoclonal antibodies (mAbs) were initially developed for intravenous (IV) administration. As a means to improve mAb drug-ability and the patient experience, subcutaneous (SC) administration is an increasingly important delivery route for mAbs. Unlike IV administration, bioavailability limitations for antibodies have been reported following SC injection and can dictate whether a mAb is administered via this parenteral route. The SC bioavailability of antibodies has been difficult to predict, and it can be variable and partial, with values ranging from ~50% to 100%. The mechanisms leading to the incomplete bioavailability of some mAbs relative to others are not well understood. There are some limited data that suggest the physiochemical properties inherent to a mAb can contribute to its SC absorption, bioavailability, and in vivo fate. In this study, we evaluated the integrated influence of multiple mAb physiochemical factors on the SC absorption and bioavailability of six humanized mAbs in both rats and cynomolgus monkeys. We demonstrate the physiochemical properties of mAbs are critical to their rate and extent of SC absorption. The combination of high positive charge and hydrophobic interaction significantly reduced the rate of the evaluated mAb’s SC absorption and bioavailability. Reduction or balancing of both these attributes via re-engineering the mAbs restored desirable properties of the molecules assessed. This included reduced association with SC tissue, improvements in mAb absorption from the SC space and overall SC bioavailability. Our findings point to the importance of evaluating the relative balance between various physiochemical factors, including charge, hydrophobicity, and stability, to improve the SC drug-ability of mAbs for selecting or engineering mAbs with enhanced in vivo absorption and bioavailability following SC administration.

The testicular spread of renal cell carcinoma is extremely rare. Five cases of renal cell carcinoma metastatic to the testis are described. The patients ranged from 45 to 81 years of age. Four of the five patients had known renal cell carcinoma. The time intervals between the partial and radical nephrectomies for the primary kidney tumors and the occurrence of testicular metastases ranged from 29 to 34 months. In one patient, the testicular mass was the initial presentation leading to a diagnosis of renal cell carcinoma. There were three ipsilateral metastases, one contralateral metastasis, and one bilateral metastasis. The metastatic deposits ranged in size from 2.0 to 5.7 cm. One case had multiple metastatic tumor nodules. All of the metastatic tumors had clear cell histological features, microscopically concordant with the primary renal cell carcinoma subtype. Three patients died of the disease 17 to 42 months after orchiectomy. One patient is alive with additional metastatic lesions 13 months after orchiectomy. One patient had been free of disease at 87 months after orchiectomy but is now on targeted therapy for an additional metastasis at 93 months after orchiectomy. To date, this report is one of the largest single series of patients with renal cell carcinoma metastatic to the testis, and it has the longest follow-up and survival among all the reported cases.

Wave-induced fluid flow is the main cause of seismic attenuation and dispersion. So the estimated velocity dispersion information can be used to identify reservoir fluid and effectively reduce the risk of reservoir drilling. Using equivalence of dispersion and attenuation between poroelastic and viscoelastic media, we developed the method of FAVO (frequency-dependent amplitude variation with offset) dispersion quantitative estimation based on the analytical solution of 1D viscoelastic wave equation. Compared with the current single-interface velocity dispersion estimation method, the new nonlinear approach uses the analytical solution of 1D viscoelastic wave equation as the forward modeling engine. This method can conveniently handle the attenuation and generate the full-wave field response of a layered medium. First, the compound matrix method (CMM) was applied to rapidly obtain the analytical solution by vectorization. Further, we analyzed the seismic response characteristics through the model data to clarify the effectiveness of the forward modeling method. Then, the more reliable P-wave velocity, S-wave velocity, and density were recovered based on prestack viscoelastic waveform inversion (PVWI). Combining with the inversion results, the derivative matrix was calculated to perform nonlinear velocity dispersion estimation. Finally, the new estimation method was tested with the model and actual data. The experiments show that the developed method is clearly superior to the single-interface dispersion estimation method in accuracy and resolution. This approach can be used as a new choice reservoir fluid identification.

The human gut microbiota plays a critical role in the metabolism of dietary carbohydrates. Previous studies have illustrated that marine algae oligosaccharides could be utilized and readily fermented by human gut microbiota. However, the human gut microbiota is classified into three different enterotypes, and how this may affect the fermentation processes of marine algae oligosaccharides has not been studied. Here, using in vitro fermentation and 16 S high-throughput sequencing techniques, we demonstrate that the human gut microbiota has an enterotype-specific effect on the fermentation outcomes of marine algae oligosaccharides. Notably, microbiota with a Bacteroides enterotype was more proficient at fermenting carrageenan oligosaccharides (KOS) as compared to that with a Prevotella enterotype and that with an Escherichia enterotype. Interestingly, the prebiotic effects of marine algae oligosaccharides were also found to be enterotype dependent. Altogether, our study demonstrates an enterotype-specific effect of human gut microbiota on the fermentation of marine algae oligosaccharides. However, due to the availability of the fecal samples, only one sample was used to represent each enterotype. Therefore, our research is a proof-of-concept study, and we anticipate that more detailed studies with larger sample sizes could be conducted to further explore the enterotype-specific prebiotic effects of marine oligosaccharides.

The pick-up, migration, deposition, and clogging behaviors of fine particles are ubiquitous in many engineering applications, including contaminant remediation. Deposition and clogging are detrimental to the efficiency of environmental remediation, and their mechanisms are yet to be elucidated. Two-dimensional microfluidic models were developed to simulate the pore structure of porous media with unified particle sizes in this study. Kaolin and bentonite suspensions were introduced to microfluidic chips to observe their particle deposition and clogging behaviors. Interactions between interparticle forces and particle velocity profiles were investigated via computational fluid dynamics and discrete element method simulations. The results showed that (1) only the velocity vector toward the micropillars and drag forces in the reverse direction were prone to deposition; (2) due to the negligible weight of particles, the Stokes number implied that inertia was not the controlling factor causing deposition; and (3) the salinity of the carrying fluid increased the bentonite deposition because of the shrinkage of the diffused electrical double layer and an increase in aggregation force, whereas it had little effect on kaolin deposition.

Ocean colour data are crucial for monitoring and assessing marine ecosystems. In this study, the Data Interpolating Empirical Orthogonal Functions (DINEOF) approach was applied to the Ocean Colour Climate Change Initiative (OC-CCI), chlorophyll-a (Chl-a) and Secchi disk depth (Zsd) to completely reconstruct the missing pixels in the Bohai Sea during 1997–2019. The results of cross-validation demonstrate that the DINEOF reconstructed data have a good agreement with the satellite-measured data. Based on monthly cloud-free satellite data reconstructions, the Zsd series showed high negative correlation with log10 (Chl-a). The Zsd as a function of log10 (Chl-a) can be well fitted by the cubic polynomial in the offshore waters. The Chl-a in the entire Bohai Sea showed a significant decreasing trend (−0.013 mg/m3/year), while the Zsd exhibited a significant increasing trend (0.0065 m/year), and both had regional-seasonal variations. In addition, the ensemble empirical mode decomposition (EEMD) results reveal highly nonlinear trends of Chl-a and Zsd. The linear and nonlinear trends of Chl-a and Zsd suggest the deterioration of water quality in the Bohai Sea was not continued over the past two decades. This study presents the first simultaneous investigation of Chl-a and Zsd using the 23 years of cloud-free reconstructions in the Bohai Sea.

In June 2018, for the first time, the SURA heating facility in Russia , together with the in-orbit China Seismo-Electromagnetic Satellite (CSES), carried out a series of experiments in emitting high frequency (HF) O-mode radio waves to disturb the ionosphere. This paper reports data from those experiments, collected onboard CSES, including electric field, in-situ plasma parameters, and energetic particle flux. Five cases are analyzed, two cases in local daytime and three in local nighttime. We find that the pumping wave frequencies f0 in local daytime were close to the critical frequency of the F2 layer foF2, but no pumping waves were detected by the electric field detector (EFD) on CSES even when the emitted power reached 90 MW, and no obvious plasma disturbances were observed from CSES in those two daytime cases. But on June 16, there existed a spread F phenomena when f0 was lower than foF2 at that local daytime period. During the three cases in local nighttime, the pumping waves were clearly distinguished in the HF-band electric field at the emitted frequency with the emitted power only 30 MW; the power spectrum density of the electric field was larger by an order of magnitude than the normal background, with the propagating radius exceeding 200 km. Due to the small foF2 over SURA in June at that local nighttime period, f0 in these three cases were significantly higher than foF2, all belonging to under-dense heating conditions. As for the plasma parameters, only an increase of about 100 K in ion temperature was observed on June 12; in the other two cases (with one orbit without plasma data on June 17), no obvious plasma disturbances were found. This first joint SURA-CSES experiment illustrates that the present orbit of CSES can cross quite close to the SURA facility, which can insure an effective heating time from SURA so that CSES can observe the perturbations at the topside ionosphere excited by SURA in the near region. The detection of plasma disturbances on June 12 with under-dense heating mode in local nighttime provides evidence for likely success of future related experiments between CSES and SURA, or with other HF facilities.

Purpose: To investigate the feasibility and effectiveness of in situ formation of the loop snare technique for retrieval of foreign bodies from vessels.Materials and methods: We retrospectively reviewed in situ formation of the loop snare technique for retrieval of foreign bodies in 6 patients. After placing the guide wire and the loop of the gooseneck snare on each side of the tubes, the soft tip of the guide wire was caught with the gooseneck snare to form a new loop structure. The foreign body was retrieved with the new loop snare by combining the gooseneck snare and the guide wire. We reviewed the application of this technique in 6 patients with fractured central venous catheters without free ends.Results: With in situ formation of the loop snare technique, the internal ruptured catheter was successfully removed from all of the 6 patients in about 2 to 4 min. There were no complications such as arrhythmia or heart valve injury in the 6 patients with the distal end of the fragment in the pulmonary artery or right atrium.Conclusion: The in situ formation loop snare technique is an effective and fast means of retrieving tubular foreign bodies without free ends from vessels. Further research is needed to investigate the practical utility of the method for retrieval of all kinds of foreign bodies. Keywords: foreign body, gooseneck snare, in situ, loop snare

In defect engineering, both cation doping and oxygen vacancies play key roles in deciding the properties of oxide, and the utilization of their cooperation has attracted much interest in recent years. Here, we report an emergent magnetic phase transition near 18 K in Fe-doped SrTiO3−δ by utilizing the magnetic interactions between the doped Fe cations and oxygen vacancies. The effects of Fe dopants and oxygen vacancies on the structural and magnetic properties were characterized by a high-resolution X-ray diffraction, Raman spectroscopy, and superconducting quantum interference device. In particular, as the temperature rises across the magnetic phase transition, the coercivity of Fe-SrTiO3−δ decreases from ∼7700 Oe at 2 K to ∼104 Oe at 19 K. Our results of creating emergent magnetic phases with the coeffects of both cation dopants and oxygen vacancies could pave a way to inducing novel quantum states in epitaxial films on Fe-SrTiO3−δ single crystal substrates with the magnetic proximity effect.

Sparse immune-binding data for emerging pathogens limits the ability of existing in silico antigenicity prediction methods to aid vaccine design. Here, the authors introduce a computational method that estimates antigenic pathogen similarity based on epitope structure.

This dataset presents the mitochondrial genome variants associated with oncocytic tumors. These data were obtained by Sanger sequencing of the whole mitochondrial genomes of oncocytic tumors and the adjacent normal tissues from 32 patients. The mtDNA variants are identified after compared with the revised Cambridge sequence, excluding those defining haplogroups of our patients. The pathogenic prediction for the novel missense variants found in this study was performed with the Mitimpact 2 program.

Summary: Microglia are a key immune-competent cell type that respond to environmental and physiological changes during ischemic stroke. However, the molecular mechanisms controlling post-ischemic microglia activity are unclear. Understanding these mechanisms may ultimately reduce disease burden and allow the manipulation of microglia responses to shape the outcomes of stroke. Here, we report that, after experimentally induced stroke, ZEB1 is highly expressed in ipsilateral cerebral hemisphere, where it is upregulated mainly in microglia. Using a conditional transgenic mouse, we found that ZEB1 upregulation in microglia regulates immune responses in the CNS and alleviates brain injury after ischemic stroke. Our data indicate that ZEB1 overexpression mediates microglia responses and, in turn, inhibits the production of astrocytic CXCL1 through the TGF-β1-dependent pathway. Reduced CXCL1 leads to a decline in neutrophil infiltration into the brain, thereby reducing CNS inflammation. Our results demonstrate the importance of ZEB1 in microglia-orchestrated neuroinflammation and suggest a potential means for reducing stroke-induced neurological injury. : Li et al. show that ZEB1 overexpression mediates microglia responses and, in turn, inhibits production of astrocytic CXCL1 through the TGF-β1-dependent pathway. Reduced CXCL1 leads to the decline of neutrophil infiltration into the brain. This demonstrates the importance of ZEB1 in microglia-orchestrated neuroinflammation and suggests a potential means for reducing stroke-induced neurological injury. Keywords: microglia, ZEB1, ischemic stroke, astrocyte, neutrophil

Abstract Background Previous studies showed that the majority of developmental genes are devoid of DNA methylation at promoters even when they are repressed. Such hypomethylated regions at developmental genes are unusually large and extend well beyond proximal promoters, forming DNA methylation valleys (DMVs) or DNA methylation canyons. However, it remains elusive how most developmental genes can evade DNA methylation regardless of their transcriptional states. Results We show that DMVs are hypomethylated in development and are highly conserved across vertebrates. Importantly, DMVs are hotspots of regulatory regions for key developmental genes and show low levels of deamination mutation rates. By analyzing a panel of DNA methylomes from mouse tissues, we identify a subset of DMVs that are dynamically methylated. These DMVs are strongly enriched for Polycomb-deposited H3K27me3 when the associated genes are silenced, and surprisingly show elevated DNA methylation upon gene activation. 4C-seq analyses indicates that Polycomb-bound DMVs form insulated and self-interacting chromatin domains. Further investigations show that DNA hypomethylation is better correlated with the binding of Polycomb than with H3K27me3. In support of a role of Polycomb in DMV hypomethylation, we observe aberrant methylation in DMVs in mouse embryonic stem cells deficient in the EED protein. Finally, we show that Polycomb regulates hypomethylation of DMVs likely through ten-eleven translocation (TET) proteins. Conclusions We show that Polycomb promotes the hypomethylation of DMVs near key developmental genes. These data reveal a delicate interplay between histone modifiers and DNA methylation, which contributes to their division at distinct gene targets, allowing lineage-specifying genes to largely maintain DNA methylation-free at regulatory elements.

Point-of-care testing plays an important role in the detection of skin abnormalities. The detection of skin abnormalities requires sufficient depth and no harm. A flexible microwave biosensor based on spoof surface plasmon polaritons was designed to meet the requirements of skin abnormalities. The designed biosensor, which works at 11.3 GHz, is small and can be flexibly attached to the skin surface of any part of the human body for measurement. The health status of the skin can be evaluated by the resonant frequency and the magnitude of the reflection coefficient of the sensor. The sensor was tested on pork skin. The experiment results showed that the sensor can detect skin abnormalities such as skin burn, skin tumor, and others. Compared with other sensors, the sensor has sufficient penetration depth because of the strong penetration of microwave electromagnetic waves. It is the first flexible microwave biosensor used for skin, which involves point-of-care testing, and continuous monitoring of skin.

A UV Nonlinear optical (NLO) crystal is one of the key devices in all-solid-state laser technology, and borate halides show outstanding potential due to their abundant structural diversity and short UV cut-off edges. In this article, the sizable UV NLO crystal of K3B6O10Br (KBOB) has been grown with lead-containing and lead-free fluxes systems using the high-temperature top-seeded solution growth (TSSG) method. Energy Dispersive X-ray Spectroscopy (EDS) and transmittance spectra illustrate the influence of Pb2+ ions on the transmittance properties and laser-induced damage threshold (LDT). The thermal property, namely, thermal expansion, thermal conductivity, and thermal diffusivity curves, were characterized. Moreover, a small variation of thermal refractive indexes was analyzed to illustrate the advantage of KBOB in the application for temperature-fluctuated specific regions.

Anuran saxiphilins (Sxphs) are "toxin sponge" proteins thought to prevent the lethal effects of small-molecule neurotoxins through sequestration. Here, we present a protocol for the expression, purification, and characterization of Sxphs. We describe steps for using thermofluor, fluorescence polarization, and isothermal titration calorimetry assays that probe Sxph:saxitoxin interactions using a range of sample quantities. These assays are generalizable and can be used for other paralytic shellfish poisoning toxin-binding proteins. For complete details on the use and execution of this protocol, please refer to Chen et al. (2022).1.

Atmospheric radio refractivity has an obvious influence on the signal transmission path and communication group delay effect. The uncertainty of water vapor distribution is the main reason for the large error of tropospheric refractive index modeling. According to the distribution and characteristics of water vapor pressure, temperature, and pressure, which are the basic components of the refractive index, a method for retrieving atmospheric refractivity profile based on GNSS (Global Navigation Satellite System) and meteorological sensor measurement is introduced and investigated in this study. The variation of the correlation between zenith wet delay and water vapor pressure is investigated and analyzed in detail. The partial pressure profiles of water vapor are retrieved with relevance vector machine method based on tropospheric zenith wet delay calculated by single ground-based GPS (Global Positioning System) receiver. The atmospheric temperature and pressure is calculated with the least square method, which is used to fit the coefficients of the polynomial model based on a large number of historical meteorological radiosonde data of local stations. By combining the water vapor pressure profile retrieving from single ground-based GPS and temperature and pressure profile from reference model, the refractivity profile can be obtained, which is compared to radiosonde measurements. The comparison results show that results of the proposed method are consistent with the results of radiosonde. By using over ten years’ (through 2008 to 2017) historical radiosonde meteorological data of different months at China Big-Triangle Points, i.e., Qingdao, Sanya, Kashi, and Jiamusi radiosonde stations, tropospheric radio refractivity profiles are retrieved and modeled. The comparison results present that the accuracies of refractivity profile of the proposed method at Qingdao, Sanya, Kashi, and Jiamusi are about 5.48, 5.63, 3.58, and 3.78 N-unit, respectively, and the annual average relative RMSE of refractivity at these stations are about 1.66, 1.53, 1.49, and 1.23%, respectively.

Before and after earthquakes, abnormal physical and chemical phenomena can be observed by gathering ground-based and satellite data and interpreted by the lithosphere–atmosphere–ionosphere coupling (LAIC) mechanism. In this study, we focused on the mechanism of LAIC electromagnetic radiation and investigated the seismic electromagnetic (EM) wave generated in the lithosphere by earthquakes and its global propagation process from the lithosphere through the atmosphere and into the bottom of ionosphere, in order to analyze the abnormal disturbance of ground-based and space-based observation results. First, analytic formulas of the electrokinetic effect were used to simulate the generation and propagation process of the seismic EM wave in the lithosphere, interpreted as the conversion process of the seismic wave and EM wave in porous media. Second, we constructed a three-dimensional Earth–ionosphere waveguide by applying the finite-difference time-domain (FDTD) algorithm to model the global propagation process of the seismic EM wave into the atmosphere and cavity between the bottom of the ionosphere and the surface of the Earth. By combining the model of the electrokinetic effect in the lithosphere with the numerical model of the Earth–ionosphere waveguide in the atmosphere and ionosphere, we numerically simulated the global transmission process of extremely low-frequency (ELF: 3 Hz–3000 Hz) EM waves which are related to earthquakes. The propagation parameters of coseismic ELF EM waves with different duration times and center frequencies were analyzed and summarized. The simulation results demonstrate that the distribution characteristics of an electric field along longitude, latitude and altitude with time are periodic and the time interval during which an EM wave travels around the whole Earth is approximately 0.155 s when adopting the conductivity of the knee profile. We also compared the observation data with the simulation results and found that the attenuating trends of the ELF electric field are consistent. This proposed ELF EM wave propagation model of lithosphere–atmosphere–ionosphere coupling is very promising for the explanation of abnormal disturbances of ground-based and space-based observation results of ELF EM fields which are associated with earthquakes.

Gene network associated with Alzheimer’s disease (AD) is constructed from multiple data sources by considering gene co-expression and other factors. The AD gene network is divided into modules by Cluster one, Markov Clustering (MCL), Community Clustering (Glay) and Molecular Complex Detection (MCODE). Then these division methods are evaluated by network structure entropy, and optimal division method, MCODE. Through functional enrichment analysis, the functional module is identified. Furthermore, we use network topology properties to predict essential genes. In addition, the logical regression algorithm under Bayesian framework is used to predict essential genes of AD. Based on network pharmacology, four kinds of AD’s herb-active compounds-active compound targets network and AD common core network are visualized, then the better herbs and herb compounds of AD are selected through enrichment analysis.

Quantum machine learning could possibly become a valuable alternative to classical machine learning for applications in high energy physics by offering computational speedups. In this study, we employ a support vector machine with a quantum kernel estimator (QSVM-Kernel method) to a recent LHC flagship physics analysis: tt[over ¯]H (Higgs boson production in association with a top quark pair). In our quantum simulation study using up to 20 qubits and up to 50000 events, the QSVM-Kernel method performs as well as its classical counterparts in three different platforms from Google Tensorflow Quantum, IBM Quantum, and Amazon Braket. Additionally, using 15 qubits and 100 events, the application of the QSVM-Kernel method on the IBM superconducting quantum hardware approaches the performance of a noiseless quantum simulator. Our study confirms that the QSVM-Kernel method can use the large dimensionality of the quantum Hilbert space to replace the classical feature space in realistic physics data sets.

The radio-wave refraction error caused by the troposphere and ionosphere badly affects accuracy in terms of the navigation, positioning, measurement, and control of a target; it is the main source of errors in high-accuracy measurement and control systems. The high-accuracy technology needed for radio-wave refraction error correction (mainly in the troposphere and ionosphere) has been the focus of research for a long time. At present, the correction methods used for radio-wave refraction errors have a low accuracy. For an S-band radio-wave signal, the accuracy of refraction error correction can generally only reach m-level (elevation angle of 15° and above), and thus has difficulty meeting the requirements of dm-level accuracy refraction error correction for deep-space and high-orbit targets. To improve the accuracy of radio-wave refraction error correction for deep-space and high-orbit targets, a novel correction method for tropospheric and ionospheric range error due to refraction is proposed in this study, on the basis of the measured data from a water vapor radiometer and dual-frequency Global Navigation Satellite System (GNSS). The comprehensive calibration test is conducted in combination with the Chinese Area Positioning System (CAPS) in Kunming. Results show that this method can effectively correct the range error due to refraction that is caused by the troposphere and ionosphere. For an S-band radio-wave signal, the accuracy of refraction error correction can reach dm-level accuracy (elevation angle of 15° and above), which is 50% higher than that achieved with traditional methods. This work provides an effective support system for major projects, such as lunar exploration and Mars exploration.

Early pregnancy failure occurs when a mature embryo attaches to an unreceptive endometrium. During the formation of a receptive endometrium, extracellular vesicles (EVs) of the uterine fluids (UFs) deliver regulatory molecules such as small RNAs to mediate intrauterine communication between the embryo and the endometrium. However, profiling of small RNAs in goat UFs’ EVs during pregnancy recognition (day 16) has not been carried out. In this study, EVs were isolated from UFs on day 16 of the estrous cycle or gestation. They were isolated by Optiprep™ Density G radient (ODG) and verified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. Immunostaining demonstrated that CD63 was present both in the endometrial epithelium and glandular epithelium, and stain intensity was greater in the pregnant endometrium compared to the non-pregnant endometrium. Small RNA sequencing revealed that UFs’ EVs contained numerous sRNA families and a total of 106 differentially expressed miRNAs (DEMs). Additionally, 1867 target genes of the DEMs were obtained, and miRNA–mRNA interaction networks were constructed. GO and KEGG analysis showed that miRNAs were significantly associated with the formation of a receptive endometrium and embryo implantation. In addition, the fluorescence in situ hybridization assay (FISH) showed that chi-miR-451-5p was mainly expressed in stromal cells of the endometrium and a higher level was detected in the endometrial luminal epithelium in pregnant states. Moreover, the dual-luciferase reporter assay showed that chi-miR-451-5p directly binds to PSMB8 and may play an important role in the formation of a receptive endometrium and embryo implantation. In conclusion, these results reveal that UFs’ EVs contain various small RNAs that may be vital in the formation of a receptive endometrium and embryo implantation.

Previous studies have suggested that polysaccharide from Enteromorpha clathrata (ECP) could be used as a potential prebiotic to treat dysbiosis-associated diseases. However, whether it has any therapeutic effects on obesity has not been investigated. In the present study, we explored the anti-obesity effect of ECP and illustrated that it can significantly reduce the body weight and decrease the serum levels of triacylglycerol and cholesterol in high-fat diet (HFD)-fed mice. As revealed by 16S rRNA high-throughput sequencing and bioinformatic analysis, HFD remarkably changed the composition of the gut microbiota and promoted the growth of opportunistic pathogens such as Mucispirillum, Desulfobacterota and Alphaproteobacteria in obese mice. Interestingly, ECP improved intestinal dysbiosis caused by HFD and reshaped the structure of the gut microbiota in diseased mice by increasing the abundance of butyrate-producing bacterium, Eubacterium xylanophilum, in the gut. Altogether, we demonstrate for the first time an anti-obesity effect of ECP and shed new light into its therapeutic mechanisms from the perspective of gut microbiota. Our study will pave the way for the development of ECP as new prebiotic for the treatment of obesity and its associated disorders.

The trapping layer refers to the atmospheric layer with vertical gradient of atmospheric refractivity less than −157 N-Units/km or vertical gradient of atmospheric modified refractivity 0 M-unit/km, which has a significant impact on radar and radio communication systems. Based on COSMIC and other radio occultation data, we show the statistical characteristics of the global trapping layer during 2005–2020.The statistical results show that the occurrence rate of the trapping layers is mainly concentrated between 50°S and 50°N, and higher occurrences of the trapping layers with more than 50% mainly occur in the boundary area between ocean and land, such as the northwest coastal area of Mexico, the west coastal area of Africa, the Mediterranean Sea, the Red Sea and the Arabian Sea, and the northwest area of Australia, etc. The altitude of the trapping layer is lower near the land and increases with the distance away from the coastline. The intensity is mainly between 6 M-unit and 24 M-unit (an M-unit is the unit of atmospheric modified refractivity), and the average value in some regions is above 24 M-unit, such as in the Arabian Sea area. In addition, the thickness of the trapping layer is between 50 and 240 m, and is generally larger over the ocean than over the land. These results reveal that the generation of the trapping layer is the result of the interaction of various background environmental factors such as radiation band migration, trade winds, monsoons, solar radiation heating, sea–land breezes and so on.

In this paper, a deep learning long-short-term memory (LSTM) method is applied to the forecasting of the critical frequency of the ionosphere F2 layer (foF2). Hourly values of foF2 from 10 ionospheric stations in China and Australia (based on availability) from 2006 to 2019 are used for training and verifying. While 2015 and 2019 are exclusive for verifying the forecasting accuracy. The inputs of the LSTM model are sequential data for the previous values, which include local time (LT), day number, solar zenith angle, the sunspot number (SSN), the daily F10.7 solar flux, geomagnetic the Ap and Kp indices, geographic coordinates, neutral winds, and the observed value of foF2 at the previous moment. To evaluate the forecasting ability of the deep learning LSTM model, two different neural network forecasting models: a back-propagation neural network (BPNN) and a genetic algorithm optimized backpropagation neural network (GABP) were established for comparative analysis. The foF2 parameters were forecasted under geomagnetic quiet and geomagnetic disturbed conditions during solar activity maximum (2015) and minimum (2019), respectively. The forecasting results of these models are compared with those of the international reference ionosphere model (IRI2016) and the measurements. The diurnal and seasonal variations of foF2 for the 4 models were compared and analyzed from 8 selected verification stations. The forecasting results reveal that the deep learning LSTM model presents the optimal performance of all models in forecasting the time series of foF2, while the IRI2016 model has the poorest forecasting performance, and the BPNN model and GABP model are between two of them.

Natural populations of bigleaf maple (Acer macrophyllum Pursh) trees contain, at low frequency, individuals with stems that have attractive and valuable wavy grain in the wood. To maintain the genotype of these individuals, vegetative propagation is desired. To enable propagation from the limited amount of plant tissue that is often available, an in vitro micropropagation procedure was developed. A mix of wild trees was used as source material to generate a procedure that is genotype unspecific. Among tested basal media, DKW medium resulted in the highest frequency of growing shoots. For multiplication of shoots, removal of the apex of shoot explants was instrumental, presumably because this treatment broke a strong apical dominance in this species. Of tested hormone and hormone combinations, 0.1 μM thidiazuron produced the best results with an average of 3.2 axillary shoots per explant with an average of 3.7 nodes per axillary shoot after 1 month. Although rooting did not require hormone treatment, a 68% frequency of rooting was obtained on ½ MS supplemented with 1 μM IBA, 27% higher than hormone-free media. Taken together, we have developed a procedure for propagation of bigleaf maple from a limited amount of tissues that can be used to multiply various genotypes of interest.