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Abstract Background Tumor-associated macrophages (TAMs) and tumor cells are important components of the tumor microenvironment. M2 polarization of TAMs, which is a major actor in breast cancer malignancy and metastasis, can be induced by breast cancer cells. However, the potential mechanisms of the interaction between breast cancer cells and TAMs remain unclear. Methods The candidate breast cancer-associated long non-coding RNAs (lncRNAs) were analyzed using the GEO database. Functional assays, including MTT assay, Transwell assay, and EdU labeling detection, were performed to investigate the oncogenic role of linc00514 in breast cancer progression. The co-culture and ELISA assays were used to assess the role of linc00514 in macrophage recruitment and M2 polarization. RNA immunoprecipitation, RNA pull-down, and luciferase reporter assays were applied to determine the mechanism of linc00514 in breast cancer metastasis. Mouse xenograft models, mouse pulmonary metastatic models, and mouse primary tumor models were used to assess the role of linc00514 in M2 macrophage polarization and breast cancer tumorigenicity. Results Linc00514 was highly expressed in clinical breast cancer tissues and breast cancer cell lines. Overexpression of linc00514 promoted the proliferation and invasion of breast cancer cells and increased xenograft tumor volumes and pulmonary metastatic nodules. Overexpression of linc00514 also increased the percentage of macrophages expressing M2 markers CD206 and CD163. Mechanistically, linc00514 promoted Jagged1 expression in a transcriptional manner by increasing the phosphorylation of a transcription factor STAT3. Subsequently, Jagged1-mediated Notch signaling pathway promoted IL-4 and IL-6 secretions in breast cancer cells and ultimately inducing M2 polarization of macrophages. Conclusion Linc00514 plays an important role in regulating breast cancer tumorigenicity and M2 macrophage polarization via Jagged1-mediated Notch signaling pathway.

Abstract. Aberrant T cell activation is a major cause of aplastic anemia (AA) pathogenesis. Recent studies have shown that miRNAs regulate T cell activation and are involved in AA. A previous study found that miR-214 was significantly up-regulated upon T cell activation in a CD28-dependent fashion by targeting PTEN. However, the expression characteristics of miR-214 and its target genes in AA have not been defined. In this study, target genes for miR-214 were predicted and confirmed by bioinformatics and luciferase reporter assays. The expression levels of miR-214 and target genes were detected in 36 healthy individuals and 35 patients with AA in peripheral blood mononuclear cells by real-time quantitative reverse transcriptase-polymerase chain reaction. Bioinformatics and luciferase reporter assays identified that miR-214 could bind to the A20 3′ untranslated regions. Significantly increased miR-214 and the decreased A20 expression level were detected in the AA patients compared with the healthy group. In addition, significantly increased miR-214 was found in non-severe aplastic anemia compared with severe aplastic anemia patients. These results suggested that the A20 gene was a potential target of miR-214, and elevated miR-214 might medicate T cell activation at least in part by regulating A20 expression in AA. We firstly confirmed that miR-214 regulated A20 expression, and aberrant miR-214/A20 expression might contribute to immunopathology in AA. The miR-214 expression might be used as a potential biomarker that assisted in diagnosing AA severity.

The spin Hall effect of light, associated with spin-orbit interactions, describes a transport phenomenon with optical spin-dependent splitting, leading to a plethora of applications such as sensing, imaging, and spin-controlled nanophotonics. Although geometric meatsurfaces can mimic photonic spin Hall effect by spatially splitting left-hand circularly polarized and right-hand circularly polarized states of electromagnetic waves with anomalous refraction or reflection angles, the geometric phase generated by metasurfaces hinders metalenses to realize simultaneous focusing of different spin states, limiting further applications. Here, we propose and experimentally demonstrate an approach to realizing a spin Hall metalens that can focus terahertz waves with different spin states and flexibly manipulate spin-dependent focal points in multiple spatial dimensions based on a pure geometric phase. A dielectric metasurface consisting of micropillars with identical shape and different in-plane orientations is designed to realize the multidimensional manipulation of photonics spin Hall effect in terahertz region. Furthermore, helicity-dependent imaging is demonstrated by the terahertz spin Hall metalens. The uniqueness and robust approach for manipulating spin photons may have a significant impact on designing ultra-compact and multifunctional devices and spin photonics devices.

Aim: In this study, we examined the effects of branched silicon tube (BST) and temporary closed circle (TCC) in a Beagle dog model of multiple transection of small intestine and discontinuities suspected intestinal necrosis with hemorrhagic shock. Materials and Methods: Ten male Beagle dogs were randomly divided into two groups. Hemorrhagic shock was induced by bleeding. Intestine was severed. Suspected intestinal necrotic model by ligating the mesenteric vessels was established, with a small tertiary mesenteric vessel reserved. Fracted intestines were ligated (IL group, n = 5) or reconnected with BST (IR group, n = 5). The abdominal cavity was temporarily closed with TCC. Definitive surgery was conducted after 24 h. Results: There was no statistical difference between two groups in the weight of dogs, their blood loss, fluid resuscitation, operation time of early emergency treatment (EET). After definitive surgery, all dogs in IR group and 3 dogs in IL groups were alive. 18 (90%) suspicious necrotic intestinal segments in IL group became necrotic, but 20 (80%) segments in IR group didn't develop obvious changes (p

Abstract Background Gastric cancer (GC) treatment is determined by accurate tumor staging. The value of tumor deposit (TD) in prognostic prediction staging system is not yet determined. Methods We retrospectively analyzed clinical information on GC patients who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital from July 2014 to June 2016. Propensity score matching (PSM) was performed to reduce the possibility of selection bias according to the presence of TD. Results Of the 1034 GC patients, 240 (23.21%) presented with TD, which was associated with younger age and larger tumor size (all P

At present, there are 31 species of Rhaphium Meigen recorded in China. In this paper, two species from Qinghai Province of China are described as new to science: Rhaphium huzhuense sp. nov., Rhaphium minhense sp. nov. A key to the Chinese species of Rhaphium is provided.

The partial effects of saving rate changes on CO2 emissions remain unclear. Here the authors found that the increase in saving rates of China has led to increments of global industrial CO2 emissions by 189 million tonnes (Mt) during 2007-2012, while global CO2 emissions would be reduced by 186 Mt if the saving rates of China decreased by 15 percentage points.

The fast-developing information technology has imposed an urgent need for effective solutions to overcome the limitations of integration density in chips with smaller size but higher performance. van der Waals heterojunctions built with two-dimensional (2D) semiconductors have been widely studied due to their 2D nature, and their unique electrical and photoelectronic properties are quite attractive in realizing multifunctional devices toward multitask applications. In this work, black phosphorus (BP)/MoS2 heterojunctions have been used to build electronic devices with various functionalities. A p-n diode is achieved based on the vertically stacked BP/MoS2 heterojunction exhibiting an ideal factor of 1.59, whereas a laterally stacked BP/MoS2 heterojunction is implemented to fabricate a photodetector that shows a photodetection responsivity of 2000 mA/W at a wavelength of 1300 nm. Furthermore, a ternary inverter has been realized using a BP field-effect transistor in-series with a lateral BP/MoS2 heterojunction. Such results have unambiguously demonstrated the superiority of BP/MoS2 heterojunction in realizing multiple functionalities and have offered a new pathway for the design and engineering of future circuitry and device integration based on novel 2D semiconductors.

The synapse is one of the fundamental elements in human brain performing functions such as learning, memorizing, and visual processing. The implementation of synaptic devices to realize neuromorphic computing and sensing tasks is a key step to artificial intelligence, which, however, has been bottlenecked by the complex circuitry and device integration. We report a high-performance charge-trapping memory synaptic device based on two-dimensional (2D) MoS2 and high-k Ta2O5–TiO2 (TTO) composite to build efficient and reliable neuromorphic system, which can be modulated by both electrical and optical stimuli. Significant and essential synaptic behaviors including short-term plasticity, long-term potentiation, and long-term depression have been emulated. Such excellent synaptic behaviors originated from the good nonvolatile memory performance due to the high density of defect states in the engineered TTO composite. The 2D synaptic device also exhibits effective switching by incident light tuning, which further enables pattern recognition with accuracy rate reaching 100%. Such experimental demonstration paves a robust way toward a multitask neuromorphic system and opens up potential applications in future artificial intelligence and sensing technology.

As important power cables for the mining mobile equipment, such as mining shearers, ethylene propylene rubber (EPR) cables often suffer from the combining effect of various stresses on site. In order to evaluate the aging state of EPR insulation, the paper carried out the multi-stress accelerated aging test on the insulation of coal mining flexible EPR cables. The infrared spectrum, elongation at break and polarization and depolarization current of cable insulation samples were measured. The insulation state of EPR cable was evaluated by using the aging factor obtained from isothermal relaxation current. Based on the failure standard of 50% elongation at break, the life formula of EPR insulation was deduced. The experimental and analytical results show that the tiny air gap was torn to the larger air gap under the mechanical stress, which leads to the increase of oxygen infiltration and promotes the thermo-oxygen reaction. The fracture energy of EPR decreases, and mechanical aging is accelerated. Aging factor and elongation at break can indicates the deterioration degree of EPR insulation. Based on the least square method and Arrhenius equation, the service life of the insulation of coal mining flexible EPR cables is deduced.

Objective To investigate the changes in the expression of fibroblast growth factor receptors 1-3 (FGFR1-3) at different stages of osteogenic differentiation and clarify the role of FGFR signaling in osteogenic differentiation. Methods Mouse osteoblasts in primary culture and osteoblast cell line MC3T3-E1 were induced for osteogenic differentiation, and the cell differentiation was identified by morphological observation, alkaline phosphatase (ALP) staining and alizarin red staining. qRT-PCR and Western blotting were used to detect the expression of FGFR1-3 and the genes involved in osteogenic differentiation, and the effect of blocking FGFR signaling on osteoblast differentiation was observed. Results The primary mouse osteoblasts were positive to ALP staining and alizarin red staining. The expression of COL 1α, RUNX2 and OPN was increased during osteogenic differentiation in both mouse osteoblasts and MC3T3-E1 cells. The expression of FGFR1, FGFR2 and FGFR3 was also increased in the cells during osteogenic differentiation, and blocking FGFR signaling significantly inhibited osteogenic differentiation of the cells, suggesting the regulatory role of FGFR signaling in osteoblast differentiation. Conclusion FGFR signaling promotes osteogenic differentiation of osteoblasts.

Through comparison, algorithm optimization, pipeline accelerated design and structural compatibility extension of a large number of mainstream algorithm, this paper propose an algorithm that is good for modulo operation structure compatibility: improved radix-4 interleaved modular multiplication algorithm. It has advantages of short path and simple structure, and has advantages in compatibility design, can achieve full flow accelerated operation, and achieve the high speed and reconfigurable design purposes. The improved radix-4 interleaved modular multiplication unit proposed in this paper can directly realize plus-minus module division and modular addition without adding extra structure, which solves the problem of the waste of independent resources. The unified modular unit is synthesized under the 65 nm CMOS process. The area is 0.117 mm2. The clock frequency is 526 MHz. A 576 bit modular multiplication and modular division are completed at 0.55 μs and 2.98 μs respectively.

Geological disaster data is a kind of multi-source heterogeneous data with multi-source, large quantity, multi-type, multi-format, multi-scale and multi-precision.It is a typical "big data".Relational database is the mainstream management method of geological disaster data at present.There are a large proportion of unstructured data in geological disaster data.Because it is difficult to manage unstructured data effectively by using relational model, the effect of this management method is not ideal.This weakness will be further amplified in the era of big data, and will have a certain impact on geological data mining and big data analysis.This paper focuses on the management mode of geological disaster data in the era of big data.Discusses the management of pan-structured geological data, application model and integration of distributed heterogeneous system.It is considered that the effective management of geological disaster data should combine file system, relational database and NoSQL, and a pan-structured geological data management and application mode based on the combination of double C model and middleware is proposed.The double C model has an implicit internal data access and management center and an explicit outer analysis and application center.Through the double C model, a variety of work can be integrated into a simple and orderly whole, such as geological data collection, management, statistics, calculation, retrieval, geological map compilation, three dimensional modeling, attribute analysis, spatial analysis and so on.

Collection of particles from a laser-driven accelerator into a conventional beamline requires careful manipulation of the beam to handle the wide energy spread, large angular divergence and short pulse lengths characteristic of laser-driven acceleration. Accurate simulation of the first few millimetres is crucial in order to optimise the collecting elements such as solenoids or quadrupole magnets. Experiments and simulations both show significant emittance growth in this collection region. We have developed a multi-particle beam dynamics model using impact-t that includes the characteristic exponentially-decaying laser-driven energy spectrum and accurately models the emittance growth due to the large energy spread. In this paper we present theoretical relationships between energy spread and emittance growth, and compare these with the simulated emittance growth. Results show excellent correspondence between theory and simulation. The effect is negligible for low-energy proton accelerators, but is important for electron accelerators and for proposed high-energy laser-driven proton accelerators.

As a critical ecosystem type, wetlands have received extensive attention from scholars worldwide. Previous studies have mostly taken the entire wetland as the research object, and there is a lack of differentiated research on wetland subsystems. Ponds are a vital component of wetland ecosystems, and they are widely distributed, provide high ecological service value, and are related to many ecosystem functions; however, they have not attracted sufficient scholarly attention. This study divided ponds into three categories according to differences in geographic location, surrounding land-use types, and ecological service functions: ponds surrounding farmland, ponds around lakes, and ponds near towns. Taking county-level cities in the Jianghuai Ecological Economic Zone as the research area, a comprehensive evaluation system was established based on the external dangers and internal vulnerabilities of pit ponds. This evaluation method was based on the current wetland evaluation system, which considers actual pond characteristics, introduces indicators that characterize pond pollution, and conducts ecological risk assessments of ponds with different ecological service functions. The results demonstrate that (1) the ecological risks of pond wetlands in the northern part of the study area are higher than those in the south; (2) the ecological risks of cultivated land and pond wetlands around towns are less than those around lakes; (3) The primary risk sources of ponds with different ecological service functions vary. The small number of ponds surrounding farmland and ponds near towns, and their unstable structure and internal fragility are the main factors affecting their ecological risk assessments. Ponds around lakes are predominately affected by natural man-made external risk factors.

Over 80% proteins consumed by the local people in Nujiang Prefecture of Southwest China, a remote and mountainous area in the Eastern Himalayas, are from pork, or Gaoligongshan pig (a landrace of Sus scrofa domestica Brisson). Previous research on the Gaoligongshan pig has focused on nutritional composition, production performance, and genetic resource characteristics, but neglected the reasons behind the local people’s practice. From 2019 to 2022, we have used ethnobiological research methods to comprehensively document the traditional rearing and management patterns and the traditional culture associated with Gaoligongshan pigs. The results show that Gaoligongshan pigs graze in mixed herds with cattle and sheep during the day and prefer to eat 23 wild plant species, in which 17 species have medicinal values. At night, the pigs are artificially fed and rest in the pigsty. The local Bai and Lisu people have developed a creative food culture, rituals, and festivals culture associated with Gaoligongshan pigs. Overall, the biocultural diversity of Gaoligongshan pig contributes to the in situ conservation of genetic diversity of this important hog landrace, and supports rural development in this remote area.

Background: Induction of anesthesia with propofol is associated with a disturbance in hemodynamics, in part due to its effects on parasympathetic and sympathetic tone. The impact of propofol on autonomic function is unclear. In this study, we investigated in detail the changes in the cardiac autonomic nervous system (ANS) and peripheral sympathetic outflow that occur during the induction of anesthesia.Methods: Electrocardiography and pulse photoplethysmography (PPG) signals were recorded and analyzed from 30 s before to 120 s after propofol induction. The spectrogram was derived by continuous wavelet transform with the power of instantaneous high-frequency (HFi) and low-frequency (LFi) bands extracted at 1-s intervals. The wavelet-based parameters were then divided into the following segments: (1) baseline (30 s before administration of propofol), (2) early phase (first minute after administration of propofol), and (3) late phase (second minute after administration of propofol) and compared with the same time intervals of the Fourier-based spectrum [high-frequency (HF) and low-frequency (LF) bands]. Time-dependent effects were explored using fractional polynomials and repeated-measures analysis of variance.Results: Administration of propofol resulted in reductions in HFi and LFi and increases in the LFi/HFi ratio and PPG amplitude, which had a significant non-linear relationship. Significant between-group differences were found in the HFi, LFi, and LFi/HFi ratio and Fourier-based HF and LF after dividing the segments into baseline and early/late phases. On post hoc analysis, changes in HFi, LFi, and the LFi/HFi ratio were significant starting from the early phase. The corresponding effect size (partial eta squared) was > 0.3, achieving power over 90%; however, significant decreases in HF and LF were observed only in the late phase. The PPG amplitude was increased significantly in both the early and late phases.Conclusion: Propofol induction results in significant immediate changes in ANS activity that include temporally relative elevation of cardiac sympathovagal balance and reduced sympathetic activity.Clinical Trial Registration: The study was approved by the Institutional Review Board of Taipei Veterans General Hospital (No. 2017-07-009CC) and is registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03613961).

Oesophageal liposarcomas are particularly rare, accounting for 1.2–1.5% of all gastrointestinal liposarcomas. Surgical resection is the usual treatment. Endoscopic resection is minimally invasive but still controversial. This current case report describes a rare case of a large oesophageal liposarcoma in a 52-year-old male that presented with 10-year history of dysphagia for dry and solid food that was exacerbated by a recent common cold. Thoracoscopic and laparoscopic oesophagectomy was performed. He did not have any dysphagia or dyspnoea 1 week postoperatively. The excised specimen consisted of a polypoid mass measuring 21.0 cm × 5.1 cm. Histological examination confirmed that it was an oesophageal liposarcoma. At 1-year postoperatively, there was no sign of recurrence. Thoracoscopy and laparoscopy can be used to treat large oesophageal masses. Long-term follow-up is required as oesophageal liposarcomas tend to recur.

Objective: Although previous studies postulated that physical and cognitive decline codeveloped in preclinical dementia, the interconnected relationship among subjective cognitive complaints (SCCs), objective cognitive performance, and physical activity remained hazy. We investigated the mediating roles of physical activity between subjective and objective cognition. Diffusion tensor imaging (DTI) was utilized to test our hypothesis that brain white matter microstructural changes underlie the physical-cognitive decline in subjective cognitive decline (SCD).Methods: We enrolled cognitively normal older adults aged > 50 years in the Community Medicine Research Center of Keelung Chang Gung Memorial Hospital during 2017–2020. Regression models analyzed mediation effects of physical activity between subjective and objective cognition. The self-reported AD8 questionnaire assessed SCCs. The SCD group, defined by AD8 score ≥ 2, further underwent diffusion MRI scans. Those who agreed to record actigraphy also wore the SOMNOwatch™ for 72 h. Spearman's correlation coefficients evaluated the associations of diffusion indices with physical activity and cognitive performance.Results: In 95 cognitively normal older adults, the AD8 score and the Montreal Cognitive Assessment (MoCA) score were mediated partially by the metabolic equivalent of the International Physical Activity Questionnaire-Short Form (IPAQ-SF MET) and fully by the sarcopenia score SARC-F. That is, the relation between SCCs and poorer cognitive performance was mediated by physical inactivity. The DTI analysis of 31 SCD participants found that the MoCA score correlated with mean diffusivity at bilateral inferior cerebellar peduncles and the pyramids segment of right corticospinal tract [p < 0.05, false discovery rate (FDR) corrected]. The IPAQ-SF MET was associated with fractional anisotropy (FA) at the right posterior corona radiata (PCR) (p < 0.05, FDR corrected). In 15 SCD participants who completed actigraphy recording, the patterns of physical activity in terms of intradaily variability and interdaily stability highly correlated with FA of bilateral PCR and left superior corona radiata (p < 0.05, FDR corrected).Conclusions: This study addressed the role of physical activity in preclinical dementia. Physical inactivity mediated the relation between higher SCCs and poorer cognitive performance. The degeneration of specific white matter tracts underlay the co-development process of physical-cognitive decline in SCD.

Climate and land use/land cover (LULC) changes alter ecosystem services that directly and indirectly affect human well-being. The impacts of management scenarios and different climate scenarios on water-related ecosystem services are uncertain in the context of future LULC and climate change interactions. Therefore, here, we analyzed the impact of future climate change and land management scenarios on water-related ecosystem services by 2030 in the Jianghuai Ecological Economic Zone (JHEEZ). Water yield and water purification were modelled for 2030, and the models were built on LULC scenarios and climate scenarios by using the Integrated Valuation of Ecosystem Services Trade-offs (InVEST) model. We used the Beijing Normal University Earth system model (BNU-ESM) for the representative concentration pathway (RCP) 4.5 and RCP8.5 scenarios, and we simulated four LULC scenarios using the future LULC simulation (FLUS) model. Four 2030 LULC scenarios, including rapid urbanization (RUS), farmland protection (FPS), ecological protection (EPS), and returning farmland to lakes scenario (RLS), were designed and compared with the year 2015 as the baseline. We found that the water yield of each LULC scenario under RCP4.5 had a decreasing trend: 10.41% (RUS), 12.43% (FPS), 13.69% (EPS), and 13.83% (RLS). However, the water yield increased under RCP8.5 and were 5.92%, 3.77%, 2.35%, and 2.18%, respectively. Water purification increased more in all LULC scenarios under the RCP8.5 than under RCP4.5. The water purification of all land-use scenarios from small to large was FPS, RUS, EPS, and RLS. Our results indicated that climate change had a greater impact than LULC on water yield, but LULC change had a greater impact on water purification. Our results provide scientific guidance for decision makers to develop better LULC policies to achieve sustainable water resource management in watershed-dominated regions. The integrated assessment approach to climate and land management also applies to other conditions to help achieve sustainable management.

An extrahepatic manifestation of nephropathies can be a feature of the chronic hepatitis C virus (HCV) infection. Albuminuria is a major risk factor for nephropathies and chronic kidney disease (CKD). The correlation between HCV genotypes and albuminuria is still unclear. In this study, investigations have been done for the biomedical tools and methodologies used in the National Health and Nutrition Examination Survey (NHANES) public database. We searched the 2007–2016 NHANES public database to retrieve data regarding the different HCV genotypes and clinical scenarios. This study attempted to investigate the impacts of HCV genetic diversity, associated comorbidities, and racial differences on albuminuria. The urine albumin/creatinine ratio (ACR) was the primary endpoint. Among 40,856 participants, 336 participants with positive and 237 with negative HCV RNA tests were analyzed, excluding 14,454 participants with negative HCV antibodies and 25,828 which were missed. After controlling for sex, race, education level, smoking, diabetes mellitus, hepatitis B, alcohol use, and body mass index (BMI) with a generalized linear equation, HCV genotype 2 was more likely than any other genotype to cause albuminuria based on the urine ACR (p < 0.001). The generalized linear equation also demonstrated a significantly higher urine ACR, including hepatitis B (p < 0.001), diabetes mellitus (p < 0.001), and smoking (p = 0.026). In summary, the patients with HCV genotype 2 presented with increased albuminuria in comparison with other HCV genotypes in this 10-year retrospective analysis. HCV infection could be a risk factor of CKD; early diagnosis and appropriate treatment may improve clinical outcomes.

Atrial fibrillation (AF) is largely underdiagnosed. Previous studies using deep neural networks with large datasets have shown that screening AF with a 12-lead electrocardiogram (ECG) during sinus rhythm (SR) is possible. However, the poor availability of these trained models and the small size of the retrievable datasets limit its reproducibility. This study proposes an approach to generate explainable features for detecting AF during SR with limited data. We collected 94,224 12-lead ECGs from 64,196 patients from Taipei Medical University Hospital. We selected ECGs during SR from 213 patients before AF diagnosis and randomly selected 247 age-matched participants without AF records as the controls. We developed a signal-processing technique, MA-UPEMD, to isolate P waves, and quantified the spatial and temporal features using principal component analysis and inter-lead relationships. By combining these features, the machine learning models yielded AUC of 0.64. We showed that, even with this limited dataset, the P wave, representing atrial electrical activity, is depicted by our proposed approach. The extracted features performed better than the bandpass filter-extracted P waves and deep neural network model. We provided a physiologically explainable and reproducible approach for classifying patients with AF during SR.

Flooding is constantly threatening the growth and yield of crops worldwide. When flooding kicks in, the soil becomes water-saturated and, therefore, the roots are the first organs to be exposed to excess water. Soon after flooding, the soil turns anoxic and the roots can no longer obtain molecular oxygen for respiration from the rhizosphere, rendering the roots dysfunctional. Rice, however, is a semi-aquatic plant and therefore relatively tolerant to flooding due to adaptive traits developed during evolution. In the present review, we have identified three key root traits, viz. cortical aerenchyma formation, a barrier to radial oxygen loss and adventitious root growth. The understanding of the physiological function, the molecular mechanisms, and the genetic regulation of these three traits has grown substantially and therefore forms the backbone of this review. Our synthesis of the recent literature shows each of the three key root traits contributes to flood tolerance in rice. One trait, however, is generally insufficient to enhance plant tolerance to flooding. Consequently, we suggest comprehensive use of all three adaptive traits in a pyramiding approach in order to improve tolerance to flooding in our major crops, in general, and in rice, in particular.

Prefabricated composite shear walls (PCSW) consisting of steel plate clapped by single-sided or double-sided prefabricated reinforced concrete (RC) panels have enormous advantages for application as lateral-resisting structures in prefabricated high-rising residential buildings. In this paper, three 1/3-scaled PCSW were manufactured and tested to investigate the seismic performance of PCSW with single-sided or double-sided prefabricated RC panels. The experimental results, including hysteretic and skeleton curves, stiffness and strength degradation, ductility, energy dissipation capability and steel frame effects, were interpreted, compared and summarized. In spite of the RC panels being the same thickness, PCSW with double-sided RC panels had the most outstanding lateral-resisting properties: the highest yield strength and bearing capacity, adequate ductility, plumper and stable hysteresis loop and excellent energy absorption capacity. Finally, a simple predicting equation with a modification coefficient to calculate the effects of boundary steel frame was summarized and proposed to calculate the lateral yield load of the PCSW. All efforts were made to give reliable technical references for the design and construction of the PCSW.

Surgery combined with chemotherapy and precision medicine is the only potential treatment for patients with colorectal cancer liver metastases (CRLM). The use of modern molecular biotechnology to identify suitable biomarkers is of great significance for predicting prognosis and formulating individualized treatment plans for these patients. BRAF mutations, particularly V600E, are widely believed to be associated with poor prognosis in patients with metastatic CRC (mCRC). However, it is unclear which specific factors affect the prognosis of CRLM patients with BRAF mutations. It is also unknown whether patients with resectable CRLM and BRAF mutations should undergo surgical treatment since there is an increased recurrence rate after surgery in these patients. In this review, we combined the molecular mechanism and clinical characteristics of BRAF mutations to explore the prognostic significance and potential targeted therapy strategies for patients with BRAF-mutated CRLM.

L-Tryptophan (Trp) is a high-value aromatic amino acid with diverse applications in food and pharmaceutical industries. Although production of Trp by engineered Escherichia coli has been extensively studied, the need of multiple precursors for its synthesis and the complex regulations of the biosynthetic pathways make the achievement of a high product yield still very challenging. Metabolic flux analysis suggests that the use of a phosphoenolpyruvate:sugar phosphotransferase system (PTS) independent glucose uptake system, i.e. the galactose permease/glucokinase (GalP/Glk) system, can theoretically double the Trp yield from glucose. To explore this possibility, a PTS− and GalP/Glk-dependent E. coli strain was constructed from a previously rationally developed Trp producer strain S028. However, the growth rate of the S028 mutant was severely impaired. To overcome this problem, promoter screening for modulated gene expression of GalP/Glk was carried out, following by a batch mode of adaptive laboratory evolution (ALE) which resulted in a strain K3 with a similar Trp yield and concentration as S028. In order to obtain a more efficient Trp producer, a novel continuous ALE system was developed by combining CRISPR/Cas9-facilitated in vivo mutagenesis with real-time measurement of cell growth and online monitoring of Trp-mediated fluorescence intensity. With the aid of this automatic system (auto-CGSS), a promising strain T5 was obtained and fed-batch fermentations showed an increase of Trp yield by 19.71% with this strain compared with that obtained by the strain K3 (0.164 vs. 0.137 ​g/g). At the same time, the specific production rate was increased by 52.93% (25.28 vs. 16.53 ​mg/g DCW/h). Two previously engineered enzyme variants AroGD6G−D7A and AnTrpCR378F were integrated into the strain T5, resulting in a highly productive strain T5AA with a Trp yield of 0.195 ​g/g and a specific production rate of 28.83 ​mg/g DCW/h.

Early accurate diagnosis of patellofemoral pain syndrome (PFPS) is important to prevent the further development of the disease. However, traditional diagnostic methods for PFPS mostly rely on the subjective experience of doctors and subjective feelings of the patient, which do not have an accurate-unified standard, and the clinical accuracy is not high. With the development of artificial intelligence technology, artificial neural networks are increasingly applied in medical treatment to assist doctors in diagnosis, but selecting a suitable neural network model must be considered. In this paper, an intelligent diagnostic method for PFPS was proposed on the basis of a one-dimensional convolutional neural network (1D CNN), which used surface electromyography (sEMG) signals and lower limb joint angles as inputs, and discussed the model from three aspects, namely, accuracy, interpretability, and practicability. This article utilized the running and walking data of 41 subjects at their selected speed, including 26 PFPS patients (16 females and 10 males) and 16 painless controls (8 females and 7 males). In the proposed method, the knee flexion angle, hip flexion angle, ankle dorsiflexion angle, and sEMG signals of the seven muscles around the knee of three different data sets (walking data set, running data set, and walking and running mixed data set) were used as input of the 1D CNN. Focal loss function was introduced to the network to solve the problem of imbalance between positive and negative samples in the data set and make the network focus on learning the difficult-to-predict samples. Meanwhile, the attention mechanism was added to the network to observe the dimension feature that the network pays more attention to, thereby increasing the interpretability of the model. Finally, the depth features extracted by 1D CNN were combined with the traditional gender features to improve the accuracy of the model. After verification, the 1D CNN had the best performance on the running data set (accuracy = 92.4%, sensitivity = 97%, specificity = 84%). Compared with other methods, this method could provide new ideas for the development of models that assisted doctors in diagnosing PFPS without using complex biomechanical modeling and with high objective accuracy.

Cancer stem cell (CSC) is thought to be the major cause of radio-resistance and relapse post radiotherapy (RT). Recently ultra-high dose rate “FLASH-RT” evokes great interest for its decreasing normal tissue damages while maintaining tumor responses compared with conventional dose rate RT. However, the killing effect and mechanism of FLASH irradiation (FLASH-IR) on CSC and normal cancer cell are still unclear. Presently the radiation induced death profile of CSC and normal cancer cell were studied. Cells were irradiated with FLASH-IR (∼109 Gy/s) at the dose of 6–9 Gy via laser-accelerated nanosecond particles. Then the ratio of apoptosis, pyroptosis and necrosis were determined. The results showed that FLASH-IR can induce apoptosis, pyroptosis and necrosis in both CSC and normal cancer cell with different ratios. And CSC was more resistant to radiation than normal cancer cell under FLASH-IR. Further experiments tracing lysosome and autophagy showed that CSCs had higher levels of lysosome and autophagy. Taken together, our results suggested that the radio-resistance of CSC may associate with the increase of lysosome-mediated autophagy, and the decrease of apoptosis, necrosis and pyroptosis. To our limited knowledge, this is the first report shedding light on the killing effects and death pathways of CSC and normal cancer cell under FLASH-IR. By clarifying the death pathways of CSC and normal cancer cell under FLASH-IR, it may help us improve the understanding of the radio-resistance of CSC and thus help to optimize the future clinical FLASH treatment plan.

Ultra-high dose rate FLASH irradiation (FLASH-IR) has got extensive attention since it may provide better protection on normal tissues while maintain tumor killing effect compared with conventional dose rate irradiation. The FLASH-IR induced protection effect on normal tissues is exhibited as radio-resistance of the irradiated normal cells, and is suggested to be related to oxygen depletion. However, the detailed cell death profile and pathways are still unclear. Presently normal mouse embryonic fibroblast cells were FLASH irradiated (∼109 Gy/s) at the dose of ∼10–40 Gy in hypoxic and normoxic condition, with ultra-fast laser-generated particles. The early apoptosis, late apoptosis and necrosis of cells were detected and analyzed at 6, 12, and 24 h post FLASH-IR. The results showed that FLASH-IR induced significant early apoptosis, late apoptosis and necrosis in normal fibroblast cells, and the apoptosis level increased with time, in either hypoxic or normoxic conditions. In addition, the proportion of early apoptosis, late apoptosis and necrosis were significantly lower in hypoxia than that of normoxia, indicating that radio-resistance of normal fibroblast cells under FLASH-IR can be enhanced by hypoxia. To further investigate the apoptosis related profile and potential pathways, mitochondria dysfunction cells resulting from loss of cytochrome c (cyt c–/–) were also irradiated. The results showed that compared with irradiated normal cells (cyt c+/+), the late apoptosis and necrosis but not early apoptosis proportions of irradiated cyt c–/– cells were significant decreased in both hypoxia and normoxia, indicating mitochondrial dysfunction increased radio-resistance of FLASH irradiated cells. Taken together, to our limited knowledge, this is the first report shedding light on the death profile and pathway of normal and cyt c–/– cells under FLASH-IR in hypoxic and normoxic circumstances, which might help us improve the understanding of the FLASH-IR induced protection effect in normal cells, and thus might potentially help to optimize the future clinical FLASH treatment.

Abstract. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the third zoonotic coronavirus to have an outbreak in the first two decades of the 21st century. Human-to-human transmission of this virus has threatened thousands of lives around the world. SARS-CoV-2 shares 79% and 50% sequence homology with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Like SARS-CoV and MERS-CoV infection, evidence has shown that SARS-CoV-2 infection also causes acute tissue damage due to a pathological immune response, particularly in severe cases. T cells play an important role in virus clearance and prevention, and in this paper, we summarize dynamic changes in the T cell count, subsets, phenotype, and function in Coronavirus Disease 2019 (COVID-19) patients based on current clinical reports. This review may help to better understand the pathological immune response of T cells and facilitate making better therapeutic strategies for patients with SARS-CoV-2 infection.

Abstract Glaucoma is a leading cause of blindness characterized by progressive degeneration of retinal ganglion cells (RGCs). A well-established risk factor for the development and progression of glaucoma is elevation of intraocular pressure (IOP). However, how elevated IOP leads to RGC degeneration remains poorly understood. Here, we fabricate a facile, tunable hydrostatic pressure platform to study the effect of increased hydrostatic pressure on RGC axon and total neurite length, cell body area, dendritic branching, and cell survival. The hydrostatic pressure can be adjusted by varying the height of a liquid reservoir attached to a three-dimensional (3D)-printed adapter. The proposed platform enables long-term monitoring of primary RGCs in response to various pressure levels. Our results showed pressure-dependent changes in the axon length, and the total neurite length. The proportion of RGCs with neurite extensions significantly decreased by an average of 38 ± 2% (mean ± SEM) at pressures 30 mmHg and above (p

Microstrip line and coaxial are the two common transmission lines in microwave systems. The common interconnection method between the two transmission lines at the low frequency band is direct soldering. The coaxial inner conductor is soldered on the metal strip line of the microstrip line. The outer conductor is mounted on the ground plane of the microstrip line. This connection has little effect on the transmission of microwave signals in the low frequency band. In the millimeter wave band, this connection will result in an increase loss of the millimeter-wave signal. Therefore, a millimeter-wave band microstrip coaxial transition structure is designed. This transition structure adds a transition hole structure between the microstrip line and the coaxial, which can effectively reduce the voltage standing wave ratio and insertion loss of the microstrip-to-coaxial transition structure, and improve the performance of the overall system.

Abstract Background Antimicrobial peptides (AMPs) are essential components of the innate immune system and can protect the host from various pathogenic bacteria. The marine environment is known to be one of the richest sources for AMPs. Effective usage of AMPs and their derivatives can greatly improve the immunity and breeding survival rate of aquatic products. It is highly desirable to develop computational tools for rapidly and accurately identifying AMPs and their functional types, for the purpose of helping design new and more effective antimicrobial agents. Results In this study, we made an attempt to develop an advanced machine learning based computational approach, MAMPs-Pred, for identification of AMPs and its function types. Initially, SVM-prot 188-D features were extracted that were subsequently used as input to a two-layer multi-label classifier. In specific, the first layer is to identify whether it is an AMP by applying RF classifier, and the second layer addresses the multi-type problem by identifying the activites or function types of AMPs by applying PS-RF and LC-RF classifiers. To benchmark the methods,the MAMPs-Pred method is also compared with existing best-performing methods in literature and has shown an improved identification accuracy. Conclusions The results reported in this study indicate that the MAMP-Pred method achieves high performance for identifying AMPs and its functional types.The proposed approach is believed to supplement the tools and techniques that have been developed in the past for predicting AMPs and their function types.

The surface of EA4T steel was repaired by ultrasonic vibration assisted laser cladding.The influence of ultrasonic vibration on the forming quality, microstructure and phase composition of laser cladding of EA4T steel were compared and analyzed by optical microscopy (OM),scanning electron microscopy(SEM),X ray diffraction(XRD),and the microhardness of the cladding layer and matrix was tested by microhardness tester.The results show that the cladding forming quality is improved, and the dendritic structure with strong original orientation is broken under the effect of ultrasonic vibration,which reduces the segregation of dendrites within the cladding layer.At the same time,ultrasonic vibration refined grain, promotes the precipitation of Cr23C6 carbide on the dendrites, but it does not change the phase composition of cladding layer.Compared with that without ultrasonic vibration applied,the microhardness distribution of cladding layer is more uniform under the ultrasonic vibration, the average microhardness of cladding layer is increased by 126.2HV0.2,and the average microhardness of heat-affected zone is decreased by 31.2HV0.2.

Abstract Background Bradykinin, a vasoactive peptide, has many biological functions. For example, it accelerates angiogenesis. Thus, we studied the effects of bradykinin on the survival of perforator flaps. Methods Averagely, 50 male Sprague–Dawley rats were divided into control and bradykinin groups and underwent procedures to the multiterritory perforator flap. Areas of flap survival were tested 7 days later. Flap perfusion was evaluated by laser Doppler imaging. We assessed the extent of autophagy by determining LC3-II/I, Beclin 1, and p62. Flap angiogenesis was assessed by immunohistochemistry and H&E staining. We measured the level of vascular endothelial growth factor (VEGF) protein using western blot. We assessed oxidative stress by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) levels. The apoptotic index was also evaluated by western blot, and we determined nitric oxide (NO) production using an NO assay kit. Results The bradykinin group exhibited significantly larger areas of flap survival, higher blood supply, and more neovascularization. The bradykinin group also had higher SOD activity, higher VEGF expression and NO content, and reduced MDA compared to the control group. Rats treated with bradykinin also had lower levels of apoptosis and autophagy relative to the control group. Conclusion Our results suggest that bradykinin promotes the survival of multiterritory perforator flaps by increasing angiogenesis, promoting the release of NO, suppressing apoptosis, reducing oxidative stress, and inhibiting autophagy.

Empirical mode decomposition (EMD) is an extensively utilized tool in a time-frequency analysis. However, disturbances, such as impulse noise, can result in a mode-splitting effect, in which one physically meaningful component is split into two or more intrinsic mode functions (IMFs). In this paper, we propose a novel method, minimum arclength EMD (MA-EMD), to robustly decompose time series data with impulse-like noises. The idea is to apply a minimum arclength criterion to adjust the knot positions of impulses during the sifting process in EMD. In this way, the impulse-like artifact is extracted with the first IMF, and the mode splitting effect of the latter decomposition is alleviated. Furthermore, when the first IMF contains the desired information, we separate the spikes and the first IMF by adding a pair of masking signals. For using this masking-aided MA-EMD (MAMA-EMD) method, we also mathematically derived the appropriate ranges of the frequency and the amplitude of the masking signal. The MAMA-EMD is utilized to deal with the simulated Duffing wave and four real-world data, including electrical current, vibration signals, the cyclic alternating pattern in sleep EEG (electroencephalography), and circadian of core body temperature. The results show that the MA-EMD and MAMA-EMD have a sound improvement when encountering impulse noises.

Propofol and fentanyl are commonly used agents for the induction of anesthesia, and are often associated with hemodynamic disturbances. Understanding pharmacodynamic impacts is vital for parasympathetic and sympathetic tones during the anesthesia induction period. Inspired by the thermodynamic interaction between drug concentrations and effects, we established a machine-learning-based response surface model (MLRSM) to address this predicament. Then, we investigated and modeled the biomedical phenomena in the autonomic nervous system. Our study prospectively enrolled 60 patients, and the participants were assigned to two groups randomly and equally. Group 1 received propofol first, followed by fentanyl, and the drug sequence followed an inverse procedure in Group 2. Then, we extracted and analyzed the spectrograms of electrocardiography (ECG) and pulse photoplethysmography (PPG) signals after induction of propofol and fentanyl. Eventually, we utilized the proposed MLRSM to evaluate the relationship between anesthetics and the integrity/balance of sympathetic and parasympathetic activity by employing the power of high-frequency (HF) and low-frequency (LF) bands and PPG amplitude (PPGA). It is worth emphasizing that the proposed MLRSM exhibits a similar mathematical form to the conventional Greco model, but with better computational performance. Furthermore, the MLRSM has a theoretical foundation and flexibility for arbitrary numbers of drug combinations. The modeling results are consistent with the previous literature. We employed the bootstrap algorithm to inspect the results’ consistency and measure the various statistical fluctuations. Then, the comparison between the modeling and the bootstrapping results was used to validate the statistical stability and the feasibility of the proposed MLRSM.

The highly contagious nature and 100% fatality rate contribute to the ongoing and expanding impact of the African swine fever virus (ASFV), causing significant economic losses worldwide. Herein, we developed a cascaded colorimetric detection using the combination of a CRISPR/Cas14a system, G-quadruplex DNAzyme, and microfluidic paper-based analytical device. This CRISPR/Cas14a-G4 biosensor could detect ASFV as low as 5 copies/μL and differentiate the wild-type and mutated ASFV DNA with 2-nt difference. Moreover, this approach was employed to detect ASFV in porcine plasma. A broad linear detection range was observed, and the limit of detection in spiked porcine plasma was calculated to be as low as 42-85 copies/μL. Our results indicate that the developed paper platform exhibits the advantages of high sensitivity, excellent specificity, and low cost, making it promising for clinical applications in the field of DNA disease detection and suitable for popularization in low-resourced areas.

Sandwich structures such as corrugated cardboard offer low weight and high bending stiffness, but they are difficult to produce at the nanoscale. Here, the authors combine webbing and perforation to produce alumina ‘nanocardboard’ with ultralow areal density that recovers without damage from extreme deformation.