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The change of microvasculature is associated with the occurrence and development of many diseases. Ultrafast power Doppler imaging (uPDI) is an emerging technology for the visualization of microvessels due to the development of ultrafast plane wave (PW) imaging and advanced clutter filters. However, the low signal-to-noise ratio (SNR) caused by unfocused transmit of PW imaging deteriorates the subsequent imaging of microvasculature. Nonlocal means (NLM) filtering has been demonstrated to be effective in the denoising of both natural and medical images, including ultrasound power Doppler images. However, the feasibility and performance of applying an NLM filter on the ultrasound radio frequency (RF) data have not been investigated so far. In this study, we propose to apply an NLM filter on the spatiotemporal domain of clutter filtered blood flow RF data (St-NLM) to improve the quality of uPDI. Experiments were conducted to compare the proposed method with three different methods (under various similarity window sizes), including conventional uPDI without NLM filtering (Non-NLM), NLM filtering on the obtained power Doppler images (PD-NLM), and NLM filtering on the spatial domain of clutter filtered blood flow RF data (S-NLM). Phantom experiments, in vivo contrast-enhanced human spinal cord tumor experiments, and in vivo contrast-free human liver experiments were performed to demonstrate the superiority of the proposed St-NLM method over the other three methods. Qualitative and quantitative results show that the proposed St-NLM method can effectively suppress the background noise, improve the contrast between vessels and background, and preserve the details of small vessels at the same time. In the human liver study, the proposed St-NLM method achieves 31.05-, 24.49-, and 11.15-dB higher contrast-to-noise ratios (CNRs) and 36.86-, 36.86-, and 15.22-dB lower noise powers than Non-NLM, PD-NLM, and S-NLM, respectively. In the human spinal cord tumor, the full-width at half-maximums (FWHMs) of vessel cross Section are 76, 201, and [Formula: see text] for St-NLM, Non-NLM, and S-NLM, respectively. The proposed St-NLM method can enhance the microvascular visualization in uPDI and has the potential for the diagnosis of many microvessel-change-related diseases.

Dynamical controls on terahertz (THz) wavefronts are crucial for many applications, but available mechanism requests tunable elements with sub-micrometer sizes that are difficult to find in the THz regime. Here, different from the local-tuning mechanism, we propose an alternative approach to construct wavefront-control meta-devices combining specifically designed metasurfaces and globally tuned graphene layers. Coupled-mode-theory (CMT) analyses reveal that graphene serves as a tunable loss to drive the whole meta-device to transit from one functional phase to another passing through an intermediate regime, exhibiting distinct far-field (FF) reflection wavefronts. As a proof of concept, we design/fabricate a graphene meta-device and experimentally demonstrate that it can reflect normally incident THz wave to pre-designed directions with different polarizations under appropriate gating voltages. We finally design a graphene meta-device and numerically demonstrate that it can generate vectorial THz beams with continuously varying polarization distributions upon gating. These findings pave the road to realizing a wide range of THz applications, such as sensing, imaging, and wireless communications.

Achieving a pre-designed scattering pattern from an ultra-compact platform is highly desired for on-chip integration optics, but conventional techniques suffer from the limitations of bulky size, wavelength-scale modulation and low efficiency. Here, we propose a new strategy to efficiently generate arbitrary spin-polarized scattering far-field patterns from surface-wave (SW) excitations on a designer Pancharatnam–Berry (PB) metasurface. We find that a PB meta-atom serves as a subwavelength scatter to decouple impinging SW to a spin-polarized propagating wave (PW) with tailored amplitude and phase, and thus interference among PWs generated by scatterings at different PB meta-atoms can generate a tailored far-field pattern. As a proof of concept, we design and fabricate a series of PB metasurfaces in the microwave regime and experimentally demonstrate that they can generate desired radiation patterns within a broad frequency band, including unidirectional radiation, line/point focusing, vortex beam and hologram. These findings may stimulate important applications in on-chip integrated photonics.

As a typical chronic kidney disease (CKD), hypertensive nephrosclerosis (HN) is a common syndrome of hypertension, characterized by chronic kidney microvascular damage. Early diagnosis of microvascular damage using conventional ultrasound imaging encounters challenges in sensitivity and specificity owing to the inherent diffraction limit. Ultrasound localization microscopy (ULM) has been developed to obtain microvasculature and microvascular hemodynamics within the kidney, and would be a promising tool for the early diagnosis of CKD.In this study, the advantage of quantitative indexes obtained by using ULM (mean arterial blood flow speeds of different segments of interlobular arteries) over indexes obtained using conventional clinical serum (β2-microglobulin, serum urea nitrogen, and creatinine) and urine (24-h urine volume and urine protein) tests and ultrasound Doppler imaging (peak systolic velocity [PSV], end-diastolic velocity [EDV], and resistance index [RI]) and contrast-enhanced ultrasound imaging (CEUS; rise time [RT], peak intensity [IMAX], mean transit time [mTT], and area under the time-intensity curve [AUC]) for early diagnosis of HN were investigated. Examinations were carried out on six spontaneously hypertensive rats (SHR) and five normal Wistar-Kyoto (WKY) rats at the age of 10 weeks.The experimental results show that the indicators derived from conventional clinical inspections (serum and urine tests) and ultrasound imaging (PSV, EDV, RI, RT, IMAX, mTT, and AUC) do not show significant difference between hypertensive and healthy rats (p 0.05), while the TTP of the SHR group (28.52 ± 5.52 s) derived from CEUS is significantly higher than that of the WKY group (18.68 ± 7.32 s; p 0.05). The mean blood flow speed in interlobular artery of SHR (12.47 ± 1.06 mm/s) derived from ULM is significantly higher than that of WKY rats (10.13 ± 1.17 mm/s; p 0.01).The advantages of ULM over conventional clinical inspections and ultrasound imaging methods for early diagnosis of HN were validated. The quantitative results show that ULM can effectively diagnose HN at the early stage by detecting the blood flow speed changes of interlobular arteries. ULM may promise a reliable technique for early diagnosis of HN in the future.

Alkali (Li/Na/K) metal anodes (AMAs), because of their remarkably high energy density and low redox potential, are considered as the most promising anodes for next-generation high-energy battery systems. Nevertheless, high reactivity and uncontrollable volume change of metal anodes during plating/striping inevitably generate dendritic metal and unstable solid electrolyte interphase, inducing low Coulombic efficiency, inferior cycling stability and even safety issues. Architecture design is emerged as an effective approach to address these fatal issues and plenty of attempts have been conducted so far. Instead of simply summarizing the structure-designing strategies to modify AMAs, the review is dedicated to overviewing and categorizing the strategies of architecture design towards the challenges of AMAs by their fundamental design principles from the perspective of electrochemical reaction. Besides, the similarities and differences of three types of alkali metals, in terms of mechanical and chemical properties, have been systematically discussed. Finally, we overviewed the existing challenges, perspectives on further development direction, and outlook for practical applications for AMAs.

Bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) eradication has a relatively high rate of side effects and high cost, thus the option of a high-dose dual therapy with a high eradication rate and fewer adverse events is a consideration. However, studies of dual therapy are still scarce and are mostly single-center studies with limited generalizability. Large-scale, multicenter studies are required. Our study investigated and compared the effectiveness, adverse events, patient compliance, and costs of high-dose dual therapy with those of bismuth-containing quadruple therapy in H. pylori-infected treatment-naive patients in a prospective, multicenter, open-label, randomized controlled trial.Treatment-naive patients infected with H. pylori were randomly assigned to receive high-dose dual therapy (esomeprazole 20 mg 4 times daily and amoxicillin 1000 mg 3 times daily, for 14 days) or bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all twice daily for 14 days). The effectiveness, adverse events, patient compliance, and costs of both groups were compared.A total of 700 patients were enrolled. The high-dose dual therapy group (N = 350) achieved eradication rates of 89.4% (intention-to-treat), 90.4% (modified intention-to-treat), and 90.6% (per-protocol), which were similar to rates in the bismuth-containing quadruple therapy group (N = 350), 84.6%, 88.0%, and 88.2%, respectively (p 0.05). The high-dose dual therapy group had a lower rate of adverse events (12.9% vs. 28.1%, p 0.001) and lower costs (¥590.2 vs. ¥723.22) compared with the quadruple therapy group, respectively. The compliance of both groups was satisfactory (97.7% high-dose dual vs. 96.8% quadruple, p 0.05).High-dose dual therapy for H. pylori eradication had similar efficacy and compliance, fewer adverse events, and lower costs than bismuth-containing quadruple therapy for treatment-naive patients.

Background Evidence has shown that the traditional Chinese herbal medicine Wumei decoction (WMD) has a protective effect on ulcerative colitis. Here, we studied the anti-inflammatory effects and potential mechanisms of WMD on chronic colitis in mice. Methods A dextran sulfate sodium (DSS)–induced chronic colitis model and CD45RBhighCD4+ T cell transfer model were established in mice. Body weight, Disease Activity Index, and colon length were assessed, and histopathology was confirmed by hematoxylin and eosin staining. Colon tissue samples were collected to detect the frequencies of various immune cells, expression of cytokines, and tight junction–related proteins using flow cytometry, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. 16S ribosomal DNA sequencing was performed to distinguish differential microbiota of fecal samples. Results Severe chronic colitis was observed in mice after DSS exposure and in Rag1-/- mice reconstituted with CD45RBhighCD4+ T cells, as manifested by weight loss, hematochezia, and shortening and thickening of the colon, which were reversed by WMD treatment. WMD markedly suppressed intestinal mucosal CD4+ T cell differentiation and the secretion of proinflammatory cytokines (eg, tumor necrosis factor α, interleukin-1β, interferon γ, and IL-17A) by flow cytometry, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Moreover, WMD promoted the expression of occludin, zonula occludens-1, and E-cadherin, thereby maintaining the epithelial barrier function. Additionally, 16S ribosomal DNA sequencing revealed that WMD regulated the dysbiosis of gut microbiota in CD45RBhighCD4+ T cell-reconstituted Rag1-/- mice, evidenced by an increase of Allobaculum and Bacteroides and a decrease of Ileibacterium. Conclusions WMD ameliorates chronic colitis in mice induced by DSS or reconstituted with CD45RBhighCD4+ T cells through suppressing Th1/Th17 cell differentiation and the secretion of proinflammatory cytokines, maintaining epithelial barrier function, and improving the dysbiosis.

Background and Aims Non-invasive biomarkers in sera of patients with inflammatory bowel disease [IBD] are not currently available for rapidly and accurately diagnosing the disease. We aimed to investigate and validate the potential roles of anti-paratuberculosis-nocardia polypeptide antibodies [anti-pTNP] in the diagnosis of IBD. Methods Serum samples were collected from 502 patients with diagnosed Crohn’s disease [CD], 141 patients with ulcerative colitis [UC], and 109 healthy donors. The levels of anti-pTNPs and anti-Saccharomyces cerevisiae antibodies [ASCAs] were determined by enzyme-linked immunosorbent assay. The effects of each variable on the diagnosis were analysed by receiver operating characteristic [ROC] analysis. We also performed an estimate study by first developing a clinical prediction model, with external validation in CD patients from nine IBD medical centres in China. Results The levels of anti-pTNPs in sera of CD patients were higher than those in UC patients and healthy donors. The positive rates of anti-pTNPs were significantly higher in ileal CD patients than in ileocolonic and colonic CD patients, and the levels of anti-pTNP IgG in perianal patients were significantly higher than those in non-perianal CD patients. Of note, anti-pTNPs and perianal diseases were important predictors for active stage of CD patients. Discriminative ability to predict active CD patients was 0.918 (95% confidence interval [CI]:0.886–0.949). Conclusions Anti-pTNP functions as a novel biological marker for diagnosing CD and can be used to assess disease severity, particularly in those with lesion locations in the terminal ileum and stricturing and perianal diseases. A validated prediction model reveals that anti-pTNPs are useful for estimating the likelihood of active CD.

BACKGROUND Tissue resident memory T (TRM) cells have been reported to play a significant role in the pathogenesis and relapse of chronic eczema. AIM To compare the efficacy and safety of the intralesional injection of 5-fluorouracil (5-FU) and triamcinolone (TA) with those associated with TA alone for the treatment of chronic eczema. METHODS A total of 168 patients were randomized to 5-FU+TA or TA groups and received a one-time intralesional injection of 5-FU+TA or TA only. Biopsies were collected before and 2 wk after treatment for evaluation of histopathological changes. All patients were followed up monthly for up to 1 year. RESULTS No serious adverse event was observed in either group. Although the mean atopic dermatitis severity index scores and effective rates were comparable between the two groups after 2 wk of treatment, the relapse rate was significantly lower in the 5-FU+TA group than in the TA group. Histological examination showed significantly fewer CD8+ and CD103+ T cells but not CD4+ T cells in the 5-FU+TA group. CONCLUSION One-time intralesional injection of 5-FU+TA is effective and safe for chronic eczema treatment and can further reduce the retention of TRM cells in the lesional skin and the relapse rate of chronic eczema.

Specific patterns of lung ultrasound (LUS) images are used to assess the severity of coronavirus disease 2019 (COVID-19) pneumonia, while such assessment is mainly based on clinicians' qualitative and subjective observations. In this study, we quantitatively analyze the LUS images to assess the severity of COVID-19 pneumonia by characterizing the patterns related to the pleural line (PL) and B-lines (BLs). Twenty-seven patients with COVID-19 pneumonia, including 13 moderate cases, seven severe cases, and seven critical cases, are enrolled. Features related to the PL, including the thickness (TPL) and roughness of the PL (RPL), and the mean (MPLI) and standard deviation (SDPLI) of the PL intensities are extracted from the LUS images. Features related to the BLs, including the number (NBL), accumulated width (AWBL), attenuation coefficient (ACBL), and accumulated intensity (AIBL) of BLs, are also extracted. The correlations of these features with the disease severity are evaluated. The performances of the binary severe/non-severe classification are assessed for each feature and support vector machine (SVM) classifiers with various combinations of features as input. Several features, including the RPL, NBL, AWBL, and AIBL, show significant correlations with disease severity (all ). The classification performance is optimal using the SVM classifier using all the features as input (area under the receiver operating characteristic (ROC) curve = 0.96, sensitivity = 0.93, and specificity = 1). These findings demonstrate that the proposed method may be a promising tool for automatic grading diagnosis and follow-up of patients with COVID-19 pneumonia.

Sarcopenia is a common geriatric disorder characterized by decreased muscle strength, low muscle mass and poor physical performance. This aging-related skeletal muscle deterioration leads to adverse outcomes and severely impairs the quality of life of patients. The accumulation of dysfunctional mitochondria with aging is an important factor in the occurrence and progression of sarcopenia. Mitochondrial quality control (MQC) fundamentally ensures the normal mitochondrial functions and is comprised of four main parts: proteostasis, biogenesis, dynamics and autophagy. Therefore, any pathophysiologic factors compromising the quality control of homeostasis in the skeletal muscle may lead to sarcopenia. However, the specific theoretical aspects of these processes have not been fully elucidated. Current therapeutic interventions using nutritional and pharmaceutical treatments show a modest therapeutic efficacy; however, only physical exercise is recommended as the first-line therapy for sarcopenia, which can ameliorate skeletal muscle deficiency by maintaining the homeostatic MQC. In this review, we summarized the known mechanisms that contribute to the pathogenesis of sarcopenia by impairing normal mitochondrial functions and described potential interventions that mitigate sarcopenia through improving MQC.

The demand for emerging applications at the terahertz frequencies motivates the development of novel and multifunctional devices for the generation and manipulation of terahertz waves. In this work, we report the realization of multifunctional spintronic-metasurface emitters, which allow simultaneous beam-steering and full polarization control over a broadband terahertz beam. This is achieved through engineering individual meta-atoms with nanoscale magnetic heterostructures and, thus, implementing microscopical control over the laser-induced spin and charge dynamics. By arranging the spintronic meta-atoms in the metagrating geometry, the generated terahertz beam can be flexibly steered in space between different orders of diffraction. Furthermore, we demonstrate a simultaneous control over the terahertz polarization states at different emission angles and show that the two control capabilities are mutually independent of each other. The nanoengineered multifunctional terahertz emitter demonstrated in this work can provide a solution to the challenge associated with a growing variety of applications of terahertz technology.

Background. Breast cancer is the most common cancer in women. miR-520b had binding sites with PTEN through the bioinformatics prediction. But few studies have been conducted on miR-520b and PTEN in breast cancer. We aimed to explore the effect of miR-520b and PTEN on breast cancer and the mechanisms involved. Methods. Clinical samples of breast cancer were collected. Bioinformatics analysis was performed to screen the differentially expressed miRNAs. CD4 T cells and CD8 T cells were cocultured with MCF-7 cells in the Transwell system. Moreover, MCF-7 cells and M0 macrophage cocultured cell lines were constructed. qRT-PCR, IF, western blot, flow cytometry, and ELISA were performed to detect related factors expression. Starbase and dual-luciferase reporter assay verified the binding of miR-520b to PTEN. The tumor formation model was established to study miR-520b and PTEN effects in vivo. Results. The differentially expressed miR-520b was screened via miRNAs sequencing and cell verification. miR-520b expression was high, PTEN was low in tumor tissues, T cells and NK cells were inhibited, and macrophages were transformed into M2 type, promoting immune escape. In addition, miR-520b bound to PTEN. Then, splenic CD4 T cells and CD8 T cells were successfully sorted. During CD4 T cell differentiation to Th1 and Treg, Th1 was inhibited, and Treg was activated. We found the polarization of macrophages was related to breast cancer. The proportion of CD206 cells increased and CD68 cells decreased in the miR-520b mimics group compared with the mimic NC group. Compared with the inhibitor NC group, the proportion of CD206 cells decreased, and CD68 cells increased in the miR-520b inhibitor group. In vivo experiments showed that miR-520b inhibitor inhibited tumor growth and promoted PTEN expression. The proportion of CD3, CD4, CD8, NK1.1, CD4+IFNγ, and CD68 cells increased, while FOXP3 and CD206 cells decreased in the miR-520b inhibitor group compared with the inhibitor NC group. However, the proportion of CD3, CD4, CD8, NK1.1, CD4+IFNγ, and CD68 cells decreased, while FOXP3 and CD206 cells increased after the addition of siPTEN. Conclusions. miR-520b inhibited PTEN and aggravated breast tumors. miR-520b inhibitor enhanced CD4 and CD8 cell populations in the tumor immune microenvironment and inhibited tumor growth.

Timely diagnosis of apple tree nutrition is very important for efficient utilization of nutrients and improvement of apple yield and quality. This study aims to establish an accurate prediction model of nitrogen (N), phosphorus (P), and potassium (K) contents in apple tree leaves based on canopy hyperspectral reflectance. Two-year field experiments with four levels of N application were conducted in 2018 and 2019. The data, including canopy scale hyperspectral reflectance and leaf N, P, and K contents, were collected from young fruit stage to fruit enlargement stage. The stacked ensemble model was applied to build prediction model. The extreme learning machine (ELM) optimized by differential evolution (DE) or self-adaptive differential evolution (SaDE) algorithm and the unoptimized ELM were used to build sub-models, and the weighting strategy based on RMSE or partial least squares (PLS) was applied to combine the sub-models. Results showed that, the stacked ensemble model based on optimized ELM had achieved better prediction results, but the results of model optimized by DE algorithm were prone to over fitting. In the sub-model combination process, PLS could provide the optimal weigh to combine sub-models and correct the over fitting problem. The stacked ensemble SaDE_ELM and PLS (SE-SaDE_ELM-PLS) method for predicting N, P, K contents in apple tree leaves had achieved the best results (N, R2P = 0.844, RMSEP = 1.709 g kg−1, RRMSE = 7.654%; P, R2P = 0.931, RMSEP = 0.137 g kg−1, RRMSE = 6.402%; K, R2P = 0.725, RMSEP = 1.071 g kg−1, RRMSE = 8.747%). The SE-SaDE_ELM-PLS method was reliable for in-situ prediction of N, P, and K contents in apple tree leaves.

Background We evaluated the application value of copy number variation sequencing (CNV-seq) to analyze chromosomal abnormalities in products of conception (POCs) from first- and second- trimester miscarriages. Methods Approximately 650 POCs from spontaneous abortion were collected from April 2018 to May 2020. CNV-seq and QF-PCR were performed to determine the characteristics and frequencies of copy number variants (CNVs) with clinical significance. Clinical features were recorded. Results Clinically significant chromosomal abnormalities were identified in 355 (54.6%) POCs, including 217 (33.4%) autosomal trisomies, 42(6.5%) chromosomal monosomy and 40 (6.2%) pathogenic CNVs (pCNVs). Chromosomal trisomy mainly occurred on chromosomes 16, 22, 21, 18, and 15. Gestational week was a negative correlative factor for chromosome abnormality.Maternal age was the positive correlative factor of chromosome abnormality. However the occurrence of monosomy X was not related to maternal or gestational age. The frequency of chromosomal abnormalities in women with a normal live birth history was 55.3%, vs 54.4% in women without a normal live birth history (P > 0.05). There were no significant differences among women without, with 1, and ≥ 2 previous miscarriages history regarding the rate of chromosomal abnormalities (P > 0.05); CNVs were less frequently detected in women with advanced maternal age than in women aged ≤ 29 years and 30–34 years (P

Localized senile pruritus is a continued health problem for the elderly. This study aimed to evaluate the efficacy and safety of artemether emulsion on localized senile pruritus.Sixty patients diagnosed with senile pruritus were randomized into the artemether emulsion (1%) group or emulsion base group in a 1:1 ratio (the artemether group vs the control group). The patients used artemether emulsion or emulsion base for pruritus twice daily for 2 weeks. The pruritus visual analog scale (VAS) and the rate of adverse events were evaluated in week 0 and week 2.The VAS scores in week 2 after treatment decreased significantly compared with those before treatment in both groups (P .05). After treatment, patients receiving the artemether emulsion had significantly lower mean VAS scores compared to those who received the emulsion base (1.21 ± 1.64 vs 3.67 ± 2.97, P .05). When the VAS scores were compared between the 2 groups before treatment, the effective rate of the artemether group was significantly higher than that of the control group (χ2 = 55, P .05) in week 2 after treatment. Besides, no adverse events occurred in both groups.Both artemether emulsion and emulsion base were effective in treating localized senile pruritus, and artemether emulsion was superior to emulsion base.

We examined hypothalamic–pituitary–adrenal stress reactivity as an indicator of differential susceptibility in moderating the links between family socioeconomic status (SES) and executive function (EF) in three-year-old urban Chinese children. The participants included 77 children (36 girls) and their families. Family income, parents’ education, and level of occupation were reported by the mothers and aggregated into a composite index of family SES. We assessed the children’s biological reactivity by salivary cortisol responses to a mild stressor, which we calculated by the area under the curve with respect to increase. We measured EF skills with a series of laboratory tasks. The results revealed significant interactive effects of SES and cortisol reactivity on children’s cognitive inhibitory control. More specifically, SES was significantly related to cognitive inhibitory control for children with higher cortisol reactivity. Conversely, for children with lower cortisol reactivity, there were no significant correlations between SES and cognitive inhibitory control. Region of significance analyses indicated a moderating effect supporting the “bright side” of differential susceptibility, meaning that high cortisol reactive children were more likely to benefit from high levels of SES. The results also manifested a direct association between SES and children’s working memory, and this association was not dependent on the features of cortisol reactivity. SES did not relate to hot EF. The results highlight the SES disparity in different EF elements and may help in the development of targeted interventions.

The effect of Eurasian spring snowmelt on surface air temperature (SAT) in late spring (April–May) and early summer (June–July) and the relevant physical mechanisms during 1981–2016 are investigated. Results show that the first mode of the inter-annual Eurasian spring snowmelt represents an east–west dipole anomaly pattern, with an intense center over Siberia and another moderate center around eastern Europe. The European spring snowmelt shows an insignificant relation to the local SAT, whereas the Siberian spring snowmelt has a significant impact on the SAT in late spring and early summer. More Siberian spring snowmelt contributes to higher SAT in late spring and lower SAT in early summer via different mechanisms. In late spring, increased Siberian spring snowmelt corresponds to less local surface albedo and cloud cover, leading to the surface absorbing more shortwave radiation and thereby higher SAT. The sub-surface and deep soil moisture anomalies generated from Siberian spring snowmelt can persist into early summer. Excessive Siberian spring snowmelt corresponds to positive soil moisture anomalies, contributing to decreased sensible heat and increased cloud cover in early summer. Increased cloud cover leads to the surface receiving less shortwave radiation. Thus, lower SAT appears over Siberia in early summer due to reduced sensible heat and shortwave radiation. However, the simulation of Eurasian spring snowmelt variability and its influences on SAT via the snow hydrological effect is still a challenge for the climate models that participated in the Coupled Model Intercomparison Project phase 6.

Jiuling Deng,1,* Ying Ma,2,* Yuqiong He,1,* Hong Yang,2 Yanhong Chen,2 Liang Wang,1 Doudou Huang,1 Shi Qiu,1,* Xia Tao,2 Wansheng Chen1 1Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wansheng ChenInstitute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaTel +64 021 81886182Email chenwansheng@shutcm.edu.cnXia TaoDepartment of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of ChinaTel +64 021 81886182Email taoxia2003@126.comPurpose: Isatis indigotica (Ii) is a cruciferous herb that is widely distributed in China, and its roots and leaves have been used in two renowned antipyretic detoxicate crude drugs in Chinese Pharmacopoeia, Radix (R) and Folium (F) Isatidis. However, the pharmacodynamic material basis and underlying mechanisms of the herbal efficacy remained to be elucidated.Methods: Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was adopted for the chemical profiling of R and F Isatidis. The active ingredients were screened out through the prediction of gastrointestinal absorption and druglikeness analysis using SwissADME. A herb-ingredient-target network was constructed through target prediction of the herbal active ingredients and anti-inflammation or anti-viral properties, followed by protein–protein interaction analysis. Then, the potential relevant signaling pathways were predicted by pathway enrichment. Finally, for verification, RAW 264.7 cell line was adopted to examine the anti-inflammatory and anti-viral activities of 6 representative ingredients in Ii.Results: Seventy-three compounds have been identified from Ii through UPLC-Q-TOF-MS. A total of 17 potential active ingredients were screened through pharmacokinetics and drug-likeness evaluation using SwissADME. It was shown that key targets might include TNF, AKT1, SRC, IL2, CASP9, and CASP3 in our herb-ingredient-target network, and isovitexin, a flavonoid, tended to participate in the inflammatory response, indoles were more likely to affect the cell proliferation processes, and lignans might have a broader affinity to key targets than the other active ingredients, such as regulating immune system (targeting IL-2) and PI3K-Akt signaling pathway. In vitro, indigo and secoisolariciresinol diglucoside markedly reduced TNF-α expression in Poly (I: C)-incubated cells. Isovitexin significantly inhibited TNF-α expression, and isatin treatment markedly reduced IL-1β expression in LPS-incubated cells.Conclusion: As the pharmacodynamics material basis of Ii, indoles, lignans, and flavonoids are believed to confer beneficial properties through various cellular aspects with multiple signaling pathways involved.Keywords: Isatis indigotica, UPLC-Q-TOF-MS, network analysis, bioassay analysis

The present study aimed to investigate the associations between the trajectory of blood pressure (BP) change and the risk of subsequent dementia and to explore the differences in age, gender, and hypertension subgroups. We included 10,660 participants aged ≥ 60 years from 1998 to 2018 waves of the Chinese Longitudinal Healthy Longevity Survey. Latent growth mixture models were used to estimate BP trajectories. Cox-proportional hazard models were used to analyze the effects of BP trajectories on the risk of dementia. According to the results, stabilized systolic BP (SBP) was found to be associated with a higher risk of dementia compared with normal SBP [adjusted hazard ratio (aHR): 1.62; 95% confidence interval (CI): 1.27-2.07] and elevated SBP (aHR: 2.22; 95% CI: 1.51-3.28) in and only in the subgroups of the oldest-old, women, and subjects without hypertension at baseline. Similarly, stabilized pulse pressure (PP) was associated with a higher risk of dementia compared with normal PP (aHR: 1.52; 95% CI: 1.24-1.88) and elevated PP (aHR: 2.12; 95% CI: 1.48-3.04) in and only in the subgroups of the oldest-old, women, and subjects with hypertension at baseline. These findings suggest that stabilized SBP and PP have predictive significance for the occurrence of dementia in late life, and the factors of age, gender, and late-life hypertension should be considered when estimating the risk of BP decline on dementia.

Adopting a “pluralistic model” of trauma, the present study combines trauma theory with a theory of place to study Elizabeth Bowen’s unique way of representing trauma, namely, her utilization of place as a dimension to register trauma. It interprets The House in Paris as a reproduction of traumatic spatial experience of flux and dislocation in the interwar period. It argues that in The House in Paris (1935), places, especially houses, become alive, not only demonstrating the haunting of trauma and mimicking the traumatic psychology of the protagonists, but also revealing historical contexts behind trauma—in particular, the exclusion and isolation of Jews and people with mixed Jewish identities in the interwar period. For Bowen, the voyage of subjectivity in the interwar period renders her protagonists traumatized rather than enabling them to find an attachment to place. So detrimental is the effect that it is impossible for them to “work through” their trauma.

To investigate the predictive role of dynamic changes of plasma biomarkers in patients with viral and mycoplasma community-acquired pneumonia (CAP).From January 2020 to June 2020, 141 patients with viral and mycoplasma CAP in People's Hospital of Ningxia Hui Autonomous Region were enrolled. Pneumonia severity index (PSI) scores [grade I-II (PSI score ≤ 70), grade III (PSI score 71-90) and grade IV-V (PSI score ≥ 91)], serum amyloid A (SAA), hypersensitive C-reactive protein (hs-CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) on the 1 day after admission were compared between the different pathogens (viral and mycoplasma) or different disease severity. The change in level of SAA, hs-CRP on the third day (ΔThe level of SAA in mycoplasma group (43 cases) was significantly higher than that in virus group (98 cases) on the 1 day after admission. There were no significant differences in other plasma biomarkers between the two groups. The more severe the illness, the higher the SAA level on the 1 day after admission. The trends of other plasma biomarkers in the two groups were consistent with SAA. The levels of SAA in the patients with exacerbation of the virus group and mycoplasma group (12 cases, 9 cases) were significantly higher than those of the improved group (57 cases, 26 cases) and the stable group (29 cases, 8 cases). SAA increased gradually in the exacerbation group, decreased gradually in the improved group, and slightly increased in the stable group. ΔSAASAA is a sensitive and valuable indicator for CAP patients with viruses and mycoplasma. Dynamic monitoring of SAA can evaluate the patient's progression, prognosis, and assist diagnosis and treatment.

The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection.The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared.Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar.Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.

Mutation spectrum of TP53 in gastric cancer (GC) has been investigated world-widely, but a comparison of mutation spectrum among GCs from various regions in the world are still sparsely documented. In order to identify the difference of TP53 mutation spectrum in GCs in Eastern Europe and in East Asia, we sequenced TP53 in GCs from Eastern Europe, Lujiang (China), and Yokohama, Kanagawa (Japan) and identified the feature of TP53 mutations of GC in these regions.In total, 689 tissue samples of GC were analyzed: 288 samples from East European populations (25 from Hungary, 71 from Poland and 192 from Romania), 268 from Yokohama, Kanagawa, Japan and 133 from Lujiang, Anhui province, China. DNA was extracted from FFPE tissue of Chinese, East European cases; and from frozen tissue of Japanese GCs. PCR products were direct-sequenced by Sanger method, and in ambiguous cases, PCR product was cloned and up to 8 clones were sequenced. We used No. NC_000017.11(hg38) as the reference sequence of TP53. Mutation patterns were categorized into nine groups: six base substitutions, insertion, deletion and deletion-insertion. Within G:C A:T mutations the mutations in CpG and non-CpG sites were divided. The Cancer Genome Atlas data (TCGA, ver.R20, July, 2019) having somatic mutation list of GCs from Whites, Asians, and other ethnicities were used as a reference for our data.The most frequent base substitutions were G:C A:T transition in all the areas investigated. The G:C A:T transition in non-CpG sites were prominent in East European GCs, compared with Asian ones. Mutation pattern from TCGA data revealed the same trend between GCs from White (TCGA category) vs Asian countries. Chinese and Japanese GCs showed higher ratio of G:C A:T transition in CpG sites and A:T G:C mutation was more prevalent in Asian countries.The divergence in mutation spectrum of GC in different areas in the world may reflect various pathogeneses and etiologies of GC, region to region. Diversified mutation spectrum in GC in Eastern Europe may suggest GC in Europe has different carcinogenic pathway of those from Asia.

Global warming and its climatic and environmental effects have mainly been investigated in terms of the absolute warming rate. Little attention has been paid to the contribution of absolute warming rate to variability on various time scales of surface air temperature (SAT), which may be a more direct index for measuring the ecoclimatic effect of warming trend. The present study analyzed the role of secular warming trend in the variations of global land SAT for 1901–2016. Less than one-third of annual SAT variations were contributed by the warming trend over large parts of the globe generally. The ratios were up to two-thirds over eastern South America, parts of South Africa and the regions around the southwestern Mediterranean and Sunda islands where the absolute warming rate was moderate but the endemic species were undergoing exceptional loss of habitat. The ratios also exhibited smallest seasonal difference over these regions. Therefore, the ratio of the warming trend to the SAT variations may be a better measure compared to the absolute warming rate for the local ecoclimate. We should also pay more attention to the regions with high ratio, not only the regions with the high absolute warming rate.

BACKGROUND Liver cancer is one of the most common malignant tumors, and ranks as the fourth leading cause of cancer death worldwide. Microvascular invasion (MVI) is considered one of the most important factors for recurrence and poor prognosis of liver cancer. Thus, accurately identifying MVI before surgery is of great importance in making treatment strategies and predicting the prognosis of patients with hepatocellular carcinoma (HCC). Radiomics as an emerging field, aims to utilize artificial intelligence software to develop methods that may contribute to cancer diagnosis, treatment improvement and evaluation, and better prediction. AIM To investigate the predictive value of computed tomography radiomics for MVI in solitary HCC ≤ 5 cm. METHODS A total of 185 HCC patients, including 122 MVI negative and 63 MVI positive patients, were retrospectively analyzed. All patients were randomly assigned to the training group (n = 124) and validation group (n = 61). A total of 1351 radiomic features were extracted based on three-dimensional images. The diagnostic performance of the radiomics model was verified in the validation group, and the Delong test was applied to compare the radiomics and MVI-related imaging features (two-trait predictor of venous invasion and radiogenomic invasion). RESULTS A total of ten radiomics features were finally obtained after screening 1531 features. According to the weighting coefficient that corresponded to the features, the radiomics score (RS) calculation formula was obtained, and the RS score of each patient was calculated. The radiomics model exhibited a better correction and identification ability in the training and validation groups [area under the curve: 0.72 (95% confidence interval: 0.58-0.86) and 0.74 (95% confidence interval: 0.66-0.83), respectively]. Its prediction performance was significantly higher than that of the image features (P < 0.05). CONCLUSION Computed tomography radiomics has certain predictive value for MVI in solitary HCC ≤ 5 cm, and the predictive ability is higher than that of image features.

With inherent orthogonality, both the spin angular momentum (SAM) and orbital angular momentum (OAM) of photons have been utilized to expand the dimensions of quantum information, optical communications, and information processing, wherein simultaneous detection of SAMs and OAMs with a single element and a single-shot measurement is highly anticipated. Here, a single azimuthal-quadratic phase metasurface-based photonic momentum transformation (PMT) is illustrated and utilized for vortex recognition. Since different vortices are converted into focusing patterns with distinct azimuthal coordinates on a transverse plane through PMT, OAMs within a large mode space can be determined through a single-shot measurement. Moreover, spin-controlled dual-functional PMTs are proposed for simultaneous SAM and OAM sorting, which is implemented by a single spin-decoupled metasurface that merges both the geometric phase and dynamic phase. Interestingly, our proposed method can detect vectorial vortices with both phase and polarization singularities, as well as superimposed vortices with a certain interval step. Experimental results obtained at several wavelengths in the visible band exhibit good agreement with the numerical modeling. With the merits of ultracompact device size, simple optical configuration, and prominent vortex recognition ability, our approach may underpin the development of integrated and high-dimensional optical and quantum systems.

Vectorial optical fields (VOFs) exhibiting arbitrarily designed wavefronts and polarization distributions are highly desired in photonics. However, current methods to generate them either require complicated setups or exhibit limited functionalities, which is unfavorable for integration-optics applications. Here, we propose a generic approach to efficiently generate arbitrary VOFs based on metasurfaces exhibiting full-matrix yet inhomogeneous Jones-matrix distributions. We illustrate our strategy with analytical calculations on a model system and an experimental demonstration of a meta-device that can simultaneously deflect light and manipulate its polarization. Based on these benchmark results, we next experimentally demonstrate the generation of a far-field VOF exhibiting both a vortex wavefront and an inhomogeneous polarization distribution. Finally, we design/fabricate a meta-device and experimentally demonstrate that it can generate a complex near-field VOF—a cylindrically polarized surface plasmon wave possessing orbital angular momentum—with an efficiency of ~34%. Our results establish an efficient and ultracompact platform for generating arbitrary predesigned VOFs in both the near- and far-fields, which may find many applications in optical manipulation and communications.

This paper introduces the experimental designs and outputs of the Diagnostic, Evaluation and Characterization of Klima (DECK), historical, Scenario Model Intercomparison Project (MIP), and Paleoclimate MIP (PMIP) experiments from the Nanjing University of Information Science and Technology Earth System Model version 3 (NESM3). Results show that NESM3 reasonably simulates the modern climate and the major internal modes of climate variability. In the Scenario MIP experiment, changes in the projected surface air temperature (SAT) show robust “Northern Hemisphere (NH) warmer than Southern Hemisphere (SH)” and “land warmer than ocean” patterns, as well as an El Niño-like warming over the tropical Pacific. Changes in the projected precipitation exhibit “NH wetter than SH” and “eastern hemisphere gets wetter and western hemisphere gets drier” patterns over the tropics. These precipitation patterns are driven by circulation changes owing to the inhomogeneous warming patterns. Two PMIP experiments show enlarged seasonal cycles of SAT and precipitation over the NH due to the seasonal redistribution of solar radiation. Changes in the climatological mean SAT, precipitation, and ENSO amplitudes are consistent with the results from PMIP4 models. The NESM3 outputs are available on the Earth System Grid Federation nodes for data users.