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Social media platforms allow users worldwide to create and share information, forging vast sensing networks that allow information on certain topics to be collected, stored, mined, and analyzed in a rapid manner. During the COVID-19 pandemic, extensive social media mining efforts have been undertaken to tackle COVID-19 challenges from various perspectives. This review summarizes the progress of social media data mining studies in the COVID-19 contexts and categorizes them into six major domains, including early warning and detection, human mobility monitoring, communication and information conveying, public attitudes and emotions, infodemic and misinformation, and hatred and violence. We further document essential features of publicly available COVID-19 related social media data archives that will benefit research communities in conducting replicable and reproducible studies. In addition, we discuss seven challenges in social media analytics associated with their potential impacts on derived COVID-19 findings, followed by our visions for the possible paths forward in regard to social media-based COVID-19 investigations. This review serves as a valuable reference that recaps social media mining efforts in COVID-19 related studies and provides future directions along which the information harnessed from social media can be used to address public health emergencies.

ObjectiveHemodynamic characteristics play critical roles in aneurysm initiation and growth. This study aims to explore the effect of common hemodynamic parameters on the formation of visceral artery aneurysms (VAAs), especially those from the pancreaticoduodenal arteries or other uncommon locations, using real patients’ models.MethodsThree-dimension vessel models of 14 VAAs from 13 patients were selected and constructed from computed tomography angiography (CTA) images. Aneurysms were manually removed to perform computational fluid dynamics (CFD) simulations of the models before aneurysm formation. Flow field characteristics were obtained and compared at the aneurysm forming and para-aneurysm areas. Aneurysm forming models were categorized into high-wall-shear stress (WSS) and low-WSS groups according to WSS value at aneurysm forming versus para-aneurysm areas.ResultsComputational fluid dynamics analysis revealed that the high WSS group had significantly higher WSSmax (P = 0.038), higher time average WSS (TAWSS) (P = 0.011), higher WSS gradient (WSSG) (p = 0.036), as well as lower oscillatory shear index (OSI) (P = 0.022) compared to the low WSS group. Significant higher WSSmax (P = 0.003), TAWSS (P = 0.003), WSSG (P = 0.041) and lower OSI (P = 0.021) was observed at the aneurysm forming site compared to both upstream and downstream areas.ConclusionBoth local increase and decrease of WSS and WSS gradient were observed for the visceral artery aneurysm forming area. Computational fluid dynamics analysis could shed light on the pathogenesis of visceral artery aneurysms at uncommon vessel locations.

Karst ecosystems represent a typical heterogeneous habitat, and it is ubiquitous with varying interactive patches of rock and soil associated with differential weathering patterns of carbonate rocks. Arbuscular mycorrhizae fungi (AMF) play an important role in regulating plant growth and nutrition in heterogeneous karst habitats. However, it remains unclear how AMF affects the growth and nutrition of plants in heterogeneous karst soil with varying patches and weathering gravel. A heterogeneous experiment with Bidens pilosa L. was conducted in a grid microcosm through patching karst soil with different gravel contents. The experimental treatments included the AMF treatments inoculated with (M+) or without (M-) fungus Glomus etunicatum; the substrate patchiness treatments involved different sizes of the homogeneous patch (Homo), the heterogeneous large patch (Hetl), and the heterogeneous small patch (Hets); the substrate gravel treatments in the inner patch involved the free gravel (FG), the low gravel (LG) 20% in 80% soil, and the high gravel (HG) 40% in 60% soil. Plant traits related to growth and nutrients were analyzed by comparing substrate gravel content and patch size. The results showed that AMF was more beneficial in increasing the aboveground biomass of B. pilosa under the LG and HG substrates with a higher root mycorrhizal colonization rate than under the FG substrate with a lower root mycorrhizal colonization rate. AMF enhanced higher growth and nutrients for B. pilosa under the LG and HG substrates than under the FG substrate and under the Hets than under the Hetl. Moreover, AMF alleviated the limited supply of N for B. pilosa under all heterogeneous treatments. Furthermore, the response ratio LnRR of B. pilosa presented that the substrate gravel promoted the highest growth, N and P absorption than the substrate patchiness with M+ treatment, and the gravel content had a more effect on plant growth and nutrition as compared to the patch size. Overall, this study suggests that plant growth and nutrition regulated by AMF mainly depend on the substrate gravel content rather than the spatial patchiness in the heterogeneous karst habitat.

BackgroundPostoperative delirium (POD) is a common aging-associated postoperative complication that has received increasing attention in the context of the aging global population and the number of articles published on POD is gradually increasing. This study aimed to quantify the basic information of scholarly publications on POD and identify the most impactful literature, trends, and hotspots in POD research.Materials and methodsWe searched articles on POD through the Science Citation Index Expanded databases published from 2000 to 2020. Bibliographic information, including year, country, authorship, type, journal, funding, affiliations, subject areas, and hotspots, was collected for further analysis.ResultsA total of 2,114 articles on POD from 2000 to 2020 were identified. The highest number of studies (n = 748) were published in the United States, comprising the most total citations (13,928), followed by China (n = 278), and Germany (n = 209). Inouye, Sharon K. was the most productive author, with 66 publications on POD. The Journal of the American Geriatrics Society published the highest number of articles (n = 80), with the most total citations (4,561) and average (57.01), followed by Anesthesia and Analgesia (n = 52), and the British Journal of Anaesthesia (n = 43). Harvard University was the most productive institute, with the highest H-index (n = 46) and highest degree centrality (n = 191). The top hotspots in the field of POD during this period were “elderly,” “cardiac surgery,” “cognitive impairment,” “hip fracture,” and “intensive care unit.”ConclusionThis study provides an overview of developments in the field of POD over the past 20 years using bibliometric analysis. Overall, research on POD has flourished worldwide. The United States (US) has a relatively high academic impact owing to its productive expertise and institutions in this field. Despite much research illustrating the diagnosis and management of POD in clinical practice, more basic research is needed.

Age has important implications for health, and understanding how age manifests in the human body is the first step for a potential intervention. This becomes especially important for cardiac health, since age is the main risk factor for development of cardiovascular disease. Data-driven modeling of age progression has been conducted successfully in diverse applications such as face or brain aging. While longitudinal data is the preferred option for training deep learning models, collecting such a dataset is usually very costly, especially in medical imaging. In this work, a conditional generative adversarial network is proposed to synthesize older and younger versions of a heart scan by using only cross-sectional data. We train our model with more than 14,000 different scans from the UK Biobank. The induced modifications focused mainly on the interventricular septum and the aorta, which is consistent with the existing literature in cardiac aging. We evaluate the results by measuring image quality, the mean absolute error for predicted age using a pre-trained regressor, and demonstrate the application of synthetic data for counter-balancing biased datasets. The results suggest that the proposed approach is able to model realistic changes in the heart using only cross-sectional data and that these data can be used to correct age bias in a dataset.

Orthopedic device-related infection (ODRI) caused by Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA) biofilm may lead to persist infection and severe inflammatory osteolysis. Previous studies have demonstrated that both isobavachalcone and curcumin possess antimicrobial activity, recent studies also reveal their antiosteoporosis, anti-inflammation, and immunoregulatory effect. Thus, this study aims to investigate whether the combination of isobavachalcone and curcumin can enhance the anti-S. aureus biofilm activity of gentamicin and alleviate inflammatory osteolysis in vivo. EUCAST and a standardized MBEC assay were used to verify the synergy between isobavachalcone and curcumin with gentamicin against planktonic S. aureus and its biofilm in vitro, then the antimicrobial and immunoregulatory effect of cocktail therapy was demonstrated in a femoral ODRI mouse model in vivo by μCT analysis, histopathology, quantification of bacteria in bone and myeloid-derived suppressor cell (MDSC) in bone marrow. We tested on standard MSSA ATCC25923 and MRSA USA300, 5 clinical isolated MSSA, and 2 clinical isolated MRSA strains and found that gentamicin with curcumin (62.5–250 μg/ml) and gentamicin with isobavachalcone (1.56 μg/ml) are synergistic against planktonic MSSA, while gentamicin (128 μg/ml) with curcumin (31.25–62.5, 250–500 μg/ml) and gentamicin (64–128 μg/ml) with isobavachalcone (1.56–12.5 μg/ml) exhibit synergistic effect against MSSA biofilm. Results of further study revealed that cocktail of 128 μg/ml gentamicin together with 125 μg/ml curcumin +6.25 μg/ml isobavachalcone showed promising biofilm eradication effect with synergy against USA300 biofilm in vitro. Daily intraperitoneal administration of 20 mg/kg/day isobavachalcone, 20 mg/kg/day curcumin, and 20 mg/kg/day gentamicin, can reduce inflammatory osteolysis and maintain microarchitecture of trabecular bone during orthopedic device-related MRSA infection in mice. Cocktail therapy also enhanced reduction of MDSC M1 polarization in peri-implant tissue, suppression of MDSC amplification in bone marrow, and Eradication of USA300 biofilm in vivo. Together, these results suggest that the combination of isobavachalcone and curcumin as adjuvants administrated together with gentamicin significantly enhances its antimicrobial effect against S. aureus biofilm, and can also modify topical inflammation in ODRI and protect bone microstructure in vivo, which may serve as a potential treatment strategy, especially for S. aureus induced ODRI.

RationaleFructose-1,6-bisphosphatase (FBP1) is a tumor suppressor and a key enzyme negatively regulating Warburg effect in cancer. However, regulation of FBP1 protein expression and its exact role in prostate cancer (PCa) is largely unclear. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumor suppressor genes in human PCa. However, the role of PTEN loss in aberrant Warburg effect in cancer remains poorly understood.MethodsExpression of PTEN and FBP1 was analyzed in several PCa cell lines and prostate tumor tissues in mice. Western blot (WB) and RT-PCR approaches were used to examine how PTEN regulates FBP1 expression. Co-immunoprecipitation (co-IP) and in vivo ubiquitination assays were used to define the regulatory mechanisms. A PCa xenograft model was employed to determine the impact of PTEN regulation of FBP1 on PCa growth in vivo.ResultWe demonstrated that in a manner dependent of PI3K/AKT signal pathway PTEN regulated FBP1 expression in various PCa cell lines and tumors in mice. We confirmed that this regulation took place at the protein level and was mediated by SKP2 E3 ubiquitin ligase. Mechanistically, we showed that serine 271 phosphorylation of FBP1 by cyclin-dependent kinases (CDKs) was essential for SKP2-mediated degradation of FBP1 protein induced by PTEN loss. Most importantly, we further showed that loss of PTEN expression enhanced Warburg effect and PCa growth in mice in a manner dependent, at least partially on FBP1 protein degradation.ConclusionsOur results reveal a novel tumor-suppressive feature of PTEN in restraining FBP1 degradation and the Warburg effect. These results also suggest that prohibiting FBP1 protein degradation could be a viable therapeutic strategy for PTEN-deficient PCa.

Conventional photocatalysts generate numerous active species—primarily hydroxyl radicals (•OH)—under solar light excitation to exert photocatalytic activity for especially antibacterial effects. However, the light dependence limits their competitiveness against other antimicrobial materials since they do not work at night. Herein, a P-g-C3N4/Sr2MgSi2O7:Eu2+,Dy3+ (P-g-C3N4/SMSO) composite day–night photocatalyst is synthesized, using a model methyl orange (MO) substrate, and the impacts of trace P doping and the SMSO composite on the activity of the photocatalyst in MO degradation is investigated; Its antibacterial effect against Escherichia coli and Staphylococcus aureus on ceramic surfaces is further examined. The morphology, structure, and composition of the photocatalyst are characterized by SEM, TEM, XRD, FT-IR, and UV–vis DRS. Finally, the photocatalytic mechanism is elucidated through active species capture experiments and ESR testing. P doping and the SMSO heterojunction structure reduce the width of the forbidden band of g-C3N4 and broaden its visible-light-response range. Moreover, SMSO acts as a light source to realize long-lasting photocatalytic performance of the composite, even in the dark. The photocatalytic process produces •O2-, 1O2, and h+ active species, with •O2- and 1O2 playing the dominant role—instead of •OH as previously thought.

Background and purposeIt is crucial to evaluate the efficacy, recurrence, and metastasis of liver tumors after clinical treatment. This study aimed to investigate the value of Introvoxel Incoherent Motion (IVIM) imaging in the evaluation of rabbit VX2 liver tumors treated with Transcatheter Arterial Embolization (TAE) combined with apatinib.MethodsTwenty rabbit VX2 liver tumor models were established and randomly divided into either the experimental group (n=15) or the control group (n=5). The experimental group was treated with TAE combined with oral apatinib after successful tumor inoculation, while no treatment was administered following inoculation in the control group. IVIM sequence scan was performed in the experimental group before treatment, at 7 and 14 days after treatment. All rabbits were sacrificed after the last scan of the experimental group. Marginal tissues from the tumors of both groups were excised for immunohistochemical analysis to observe and compare the expression of microvessel density (MVD). The alterations of IVIM-related parameters of tumor tissues in the experimental group, including Apparent Diffusion Coefficient (ADC), True Diffusion Coefficient (D), Pseudodiffusion Coefficient (D*), and Perfusion Fraction (f) were compared at different periods, and the correlation between these parameters and MVD was analyzed.ResultsAfter treatment, ADC and D values significantly increased, whereas D* and f values both decreased, with statistically significant differences.(P0.05).ConclusionIVIM imaging can be employed to evaluate the efficacy of TAE combined with apatinib in rabbit VX2 liver tumors. Alterations in D and f values were closely related to the MVD of liver tumor tissues.

This study aimed to better understand the development patterns of breast muscle and glycogen reserves in goslings during pre- and post-hatching periods. The timepoints for sampling were embryonic days 23 and 27 of hatching and days 1, 4, and 7 post hatching. We found that the body weight of goslings increased with age. The small intestine developed with age and remained reasonably constant on day 4 post hatching. The breast muscle development decreased with age and stayed relatively stable on day 1 post hatching. The diameter of myofiber increased prior to hatching and then decreased while hatching. The development patterns of breast muscle glycogen reserves were similar to the diameter of myofiber. In contrast, the contents of liver glycogen began to decrease before hatching and then increased rapidly after hatching. Moreover, the expression of Myf-5 increased with age. The expression of MSTN was maintained at high levels prior to hatching, dropped immediately after hatching, and then gradually increased with age. Additionally, we also observed that the glycogen content in the breast muscle was positively correlated with the diameter of the myofiber. The liver glycogen content was positively correlated to the relative weight of the breast muscle, the diameter of the myofiber, and the breast muscle glycogen content. The development pattern of the myofiber was synchronized with the change in the MSTN/Myf-5 ratio. This study provided a profile to understand the development patterns of breast muscle, glycogen reserves, and myogenic gene expression in goslings, which was beneficial to understanding the characteristics of energy reserves during the early life of goslings.

Cells communication in response to extracellular or biophysical stimulus relies on elaborated systems of signal transduction. In the course of most signal pathway, the cascades involve signal protein complexes, which are often assembled by adaptor proteins. Tumor necrosis factor receptor type 1-associated death domain protein (TRADD) is an adaptor molecule involved in various signal pathways and mediating multiple biological activities, including cell survival, cell proliferation, cell differentiation, apoptosis, necroptosis and inflammation. TRADD contains an N terminal tumor necrosis factor receptor-associated factor 2 (TRAF2) binding domain and a C terminal death domain (DD) for interacting with multiple DD-containing proteins. Following activation of specific receptors, such as tumor necrosis factor receptor 1 (TNFR1), death receptor 3 (DR3), tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAILR1, DR4), TRAILR1 (DR5), DR6 and p75 neurotrophin receptor (p75NTR)，TRADD can bind to the receptors, serving as a platform for the recruitment of the downstream molecules for signal propagating and thus mediating various physiological and pathological processes. In this review, we provide a brief overview of the current knowledge on TRADD and discuss the roles of TRADD in infectious and inflammatory diseases, cardiovascular diseases, central nervous system diseases, cancer, endometriosis, hepatocyte proliferation, preterm birth and perinatal development.

Chromosome 1q21 aberration is one of the most common cytogenetic abnormalities in multiple myeloma, and is considered an important prognostic factor. The present study analyzed the clinical relevance and prognostic impact of 1q21 gain in 194 patients with newly diagnosed multiple myeloma treated with bortezomib-based regimens. 1q21 gain was detected in 45.9% (89/194) of patients, and those with 1q21 gain had a worse prognosis. Strikingly, our results showed that excluding the effects of other coinciding genetic anomalies, patients carrying at least four copies of 1q21 had worse survival outcome. Moreover, del(13q) strongly correlates with 1q21 gain, and the coexistence of del(13q) and 1q21 gain plays an important role in reducing PFS and OS times. Therefore, 1q21 gain should be considered a high-risk feature in multiple myeloma patients treated with a bortezomib-based regimen.

With the support of national policies and continuous emergence and innovation of emerging technologies, digital finance has developed rapidly in China. Can digital finance become a new driving force to promote quality development of economic growth? This study empirically examined the effect mechanisms of digital finance on the quality of economic growth. The study used the entropy weight and technique for order preference by similarity to an ideal solution method to construct a comprehensive index system of economic growth quality. From 2011 to 2019, the panel data of 272 cities in China were collected. The study found that digital finance can promote the quality of China’s economic growth in the long run; when digital finance development increases by one unit, the quality of economic growth will increase by 0.013%, and the effect is more significant in less developed regions. The digital finance coverage, depth of use, and degree of digitalization had a significant impact on the quality of economic growth. The mechanisms showed that digital finance can promote the quality of economic growth by promoting and upgrading the industrial structure. In addition, we used the threshold model to test the non-linear relationship between digital finance and the quality of economic growth. Furthermore, the results showed that when digital finance was at a low level, it had a negative effect on the quality of economic growth. As digital finance developed further, it had a significant effect on the quality of economic growth, and this effect gradually slowed down. Moreover, we found that digital finance played a more significant role in promoting the quality of economic growth in central and western regions and areas where traditional finance was underdeveloped. Based on this study, developing countries should strengthen the construction of digital infrastructure and give full play to the role of digital finance in improving the quality of economic growth, so as to promote sustainable and healthy economic development.

BackgroundElectronic health records (EHRs) with large sample sizes and rich information offer great potential for dementia research, but current methods of phenotyping cognitive status are not scalable. ObjectiveThe aim of this study was to evaluate whether natural language processing (NLP)–powered semiautomated annotation can improve the speed and interrater reliability of chart reviews for phenotyping cognitive status. MethodsIn this diagnostic study, we developed and evaluated a semiautomated NLP-powered annotation tool (NAT) to facilitate phenotyping of cognitive status. Clinical experts adjudicated the cognitive status of 627 patients at Mass General Brigham (MGB) health care, using NAT or traditional chart reviews. Patient charts contained EHR data from two data sets: (1) records from January 1, 2017, to December 31, 2018, for 100 Medicare beneficiaries from the MGB Accountable Care Organization and (2) records from 2 years prior to COVID-19 diagnosis to the date of COVID-19 diagnosis for 527 MGB patients. All EHR data from the relevant period were extracted; diagnosis codes, medications, and laboratory test values were processed and summarized; clinical notes were processed through an NLP pipeline; and a web tool was developed to present an integrated view of all data. Cognitive status was rated as cognitively normal, cognitively impaired, or undetermined. Assessment time and interrater agreement of NAT compared to manual chart reviews for cognitive status phenotyping was evaluated. ResultsNAT adjudication provided higher interrater agreement (Cohen κ=0.89 vs κ=0.80) and significant speed up (time difference mean 1.4, SD 1.3 minutes; P

AbstractAlthough pegmatites are volumetrically minor in the upper continental crust, these rocks host abundant rare metal deposits (e.g., Li, Be, Rb, Ta, and Nb). Pegmatites can be formed either by extensive fractional crystallization of granitic magmas or by low-degree partial melting of metasedimentary rocks. The Mao’ershan–Yuechengling composite batholith in the Nanling Range in the South China Block (SCB) is of early Paleozoic–Triassic age (440–381 and 236–204 Ma, respectively). Recently, hundreds of pegmatites associated with Nb, Ta, Be, Rb, and Li mineralization have been identified in this batholith. These pegmatites are hosted by granitic wall rocks. However, the relationships between the pegmatites and granitic wall rocks are not well constrained. To address this, we investigated the Mao’antang (MAT) and Tongzuo (TZ) pegmatites and their biotite granite wall rocks in the middle part of the Yuechengling pluton. Laser ablation inductively coupled plasma mass spectrometry zircon U–Pb ages revealed that the MAT pegmatites formed during the Permian (269 Ma) and Triassic (231 Ma) and that the MAT biotite granite wall rock records two stages of magmatic activity (271 and 231 Ma) that are coeval with the pegmatites. The TZ pegmatites probably formed during the Triassic (235 Ma), and the TZ biotite granite wall rock formed during the Silurian (435 Ma). The MAT biotite granite and pegmatites (εNdt=−12.0 to −10.6; εHft=−8.0 to −1.0), TZ pegmatites (εNdt=−10.4 to −6.1), and TZ biotite granites (εNdt=−9.1 to −8.7; εHft=−7.7 to −4.1) have enriched whole-rock Nd and zircon Hf isotopic compositions that are similar to those of early Paleozoic and Triassic S-type granites in the SCB. In addition, the whole-rock Pb isotopic compositions of the MAT and TZ pegmatites and granites are distributed along the upper crust evolution line. We suggest that the MAT and TZ biotite granites were mainly derived from Paleoproterozoic metasedimentary rocks in the middle crust. The MAT pegmatites are fractional crystallization products of the MAT biotite granites, whereas the TZ pegmatites were formed by fractional crystallization of hidden parental S-type granites. We propose that the MAT and TZ pegmatites have potential for rare metal (Nb, Ta, Be, and Li) mineralization, as they record high degrees of fractional crystallization. The MAT and TZ areas in the middle of the Yuechengling pluton are promising targets for rare metal exploration.

BackgroundCardiac power-to-left ventricular mass (power/mass) is an index reflecting the muscular hydraulic pump capability of the heart, and the E/e’ ratio is a specific indicator for identifying increased left ventricular filling pressure. Limited data exist regarding the prognostic value of incorporating power/mass and E/e’ ratio in heart failure with preserved ejection fraction (HFpEF).Materials and methodsIn total, 475 patients with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with complete baseline echocardiography data were included in our analysis. Patients were categorized into four groups according to power/mass and E/e’ ratio. The risk of outcomes was examined using Cox proportional hazards models and competing risk models.ResultsPatients with low power/mass and high E/e’ were more likely to be males (60.5%), with higher waist circumference, and had a higher prevalence of diabetes (52.1%), atrial fibrillation (50.4%), and lower estimated glomerular filtration rate (eGFR). Combined resting power/mass and E/e’ have graded correlations with left ventricular (LV) dysfunction and clinical outcomes in patients with HFpEF. After multivariable adjustments, an integrative approach combining power/mass and E/e’ remained to be a powerful prognostic predictor, with the highest HRs of clinical outcomes observed in patients with low power/mass and high E/e’ (all-cause mortality: HR 3.45; 95% CI: 1.69–7.05; P = 0.001; hospitalization for heart failure: HR 3.27; 95% CI: 1.60–6.67; P = 0.001; and primary endpoint: HR 3.07; 95% CI: 1.73–5.42; P < 0.001).ConclusionIn patients with HFpEF, an echo-derived integrated approach incorporating resting power/mass and E/e’ ratio remained to be a powerful prognosis predictor and may be useful to risk-stratify patients with this heterogeneous syndrome.Clinical Trial Registration[https://clinicaltrials.gov], identifier [NCT00094302].

CARD9-related inherited immune disorders are a major risk factor for chronic disseminated fungal infection. In addition to pathogens of Candida and dermatophytes, the environmental opportunists of the black yeast-like fungi are relatively frequent in this patient cohort. Particularly the genus Phialophora is overrepresented. We investigated two isolates of a strain of P. verrucosa residing in a CARD9 patient, sampled with a period of ten years apart. Genomes, melanization and antifungal susceptibility of progenitor and derived strains were compared, and potential adaptation to the host habitat was investigated with proteomic techniques using post-translational modification as a proxy. Global lactylation analysis was performed using high accuracy nano-LC-MS/MS in combination with enrichment of lactylated peptides from digested cell lysates, and subsequent peptide identification. The genome of the derived isolate had accumulated 6945 SNPs, of which 31 were detected in CDS. A large number of identified proteins were significantly enriched, e.g. in melanin biosynthesis. A total of 636 lactylation sites on 420 lactylated proteins were identified, which contained in 26 types of modification motifs. Lysine lactylation (Kla) was found in 23 constituent proteins of the ribosome, indicating an impact of Kla in protein synthesis. Twelve lactylated proteins participated in pathogenicity. A protein-protein interaction (PPI) network analysis suggested that protein lactylations are widely distributed influencing various biological processes. Our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in black fungi. Several large rearrangements and inversions were observed in the genome, but genomic changes could not be linked to adaptation or to known clinically relevant properties of progenitor to derived isolate; in vitro antifungal susceptibility had largely remained unaltered.

Background: It has been reported that diabetes mellitus affects 435 million people globally as a primary health care problem. Despite many therapies available, many diabetes remains uncontrolled, giving rise to irreversible diabetic complications that pose significant risks to patients’ wellbeing and survival. Scope of Review: In recent years, as much effort is put into elucidating the posttranscriptional gene regulation network of diabetes and diabetic complications; RNA binding proteins (RBPs) are found to be vital. RBPs regulate gene expression through various post-transcriptional mechanisms, including alternative splicing, RNA export, messenger RNA translation, RNA degradation, and RNA stabilization. Major Conclusions: Here, we summarized recent studies on the roles and mechanisms of RBPs in mediating abnormal gene expression in diabetes and its complications. Moreover, we discussed the potential and theoretical basis of RBPs to treat diabetes and its complications.

Structural coal has low permeability and high gas content. The increase of mining depth seriously restricts the safe mining of deep mines. Hydraulic flushing is the main means of gas extraction. The shape of the hydraulic flushing hole is an important basis to determine the pumping radius, which is widely regarded as a cylinder. However, due to the differences in the stress level, water force, friction and external moisture, the pore morphology, and permeability evolution need to be further studied. At present, the hole shape for hydraulic punching is equivalent to a cylinder in drilling design and evaluation, which is one of the important bases to determine the effective extraction radius. However, the hole shape is affected by many factors, so the scientific equivalent to a cylinder remains to be discussed. The BR-PKN equation describing the hole shape is established by introducing and combining the Bergmark–Roos equation and PKN model, and the hole’s shape is shown by MATLAB. To verify its accuracy, YZD18.5 is used as an onsite logging tool for data acquisition and analysis, and the hole section is drawn. The BR-PKN equation and permeability evolution model are simulated by COMSOL Multiphysics, and the permeability evolution law of conventional cylinder with hydraulic flushing is compared and analyzed. The results show that 1) the shape of the hydraulic punch hole is ellipsoid with three different axes, and its horizontal section is approximately an ellipse; 2) within the influence range of quasi-ellipsoid holes, the permeability changes in the long and short axis of quasi-ellipsoid holes are similar. The permeability evolution curve of the coal first increases, then decreases, and finally, flattens with the increase of distance from borehole, and the permeability of the coal body increases with the extension of extraction time); 3) the permeability of the equivalent ellipsoid pore decreases with the increase in coal water content. The effective radius in the long and short axes of the minimum cross section of the quasi-ellipsoid hole is 0.89 and 0.95 times the effective extraction radius of the equivalent cylinder, which provides a basis for a drilling layout.

Glioblastoma (GBM) is the most malignant tumor of the central nervous system in adults. Irradiation (IR) and temozolomide (TMZ) play an extremely important role in the treatment of GBM. However, major impediments to effective treatment are postoperative tumor recurrence and acquired resistance to chemoradiotherapy. Our previous studies confirm that Yin Yang 1 (YY1) is highly expressed in GBM, whereby it is associated with cell dedifferentiation, survival, and therapeutic resistance. Targeted delivery of small interfering RNA (siRNA) without blood-brain barrier (BBB) restriction for eradication of GBM represents a promising approach for therapeutic interventions. In this study, we utilize the engineering technology to generate T7 peptide-decorated exosome (T7-exo). T7 is a peptide specifically binding to the transferrin receptor. T7-exo shows excellent packaging and protection of cholesterol-modified Cy3-siYY1 while quickly releasing payloads in a cytoplasmic reductive environment. The engineered exosomes T7-siYY1-exo could deliver more effciently to GBM cells both in vitro and in vivo. Notably, in vitro experiments demonstrate that T7-siYY1-exo can enhance chemoradiotherapy sensitivity and reverse therapeutic resistance. Moreover, T7-siYY1-exo and TMZ/IR exert synergistic anti-GBM effect and significantly improves the survival time of GBM bearing mice. Our findings indicate that T7-siYY1-exo may be a potential approach to reverse the chemoradiotherapy resistance in GBM.

Background and objectiveGrowth differentiation factor-15 (GDF-15) and fibroblast growth factor-23 (FGF-23) are considered predictors of the incidence of cardiovascular diseases. The present meta-analysis aimed to elucidate the associations between GDF-15 and FGF-23 in the risk of atrial fibrillation (AF).MethodsAn electronic search was conducted in the Cochrane Library, PubMed, and Embase databases from inception until February 27, 2021. The study protocol was registered in the PROSPERO database (CRD42020182226).ResultsIn total, 15 studies that enrolled 36,017 participants were included. Both serum FGF-23 and GDF-15 were elevated in patients with AF. Analysis of categorical variables showed higher serum FGF-23 levels were associated with an increased risk of AF [relative risk (RR) = 1.28, 95% confidence interval (CI): 1.05–1.56]. In contrast, this association was not found with GDF-15 (RR = 0.91, 95% CI: 0.20–4.04). In dose-response analysis, a linear positive association was noted between serum FGF-23 levels and the risk of AF (P nonlinear = 0.9507), with a RR elevation of 7% for every 20 pg/ml increase in the serum FGF-23 levels (95% CI: 1.02–1.13). No remarkable relationship was found between serum GDF-15 levels and the risk of AF, and the overall RR for the association between a 100 ng/L increment in GDF-15 levels and AF was 1.01 (95% CI: 0.998–1.02).ConclusionOur study showed a positive linear correlation between serum FGF-23 levels and the risk of AF. However, no significant association was found between GDF-15 and the risk of AF. Further studies are warranted to clarify whether serum FGF-23 levels may be considered in predicting the risk of AF.Systematic Review Registration:http:www.york.ac.uk/inst/crd, identifier CRD42020182226.

Although there is an increasing debate about ecological consequences of environmental predictability for plant phenotype and fitness, the effect of predictability of parental environments on the offspring is still indefinite. To clarify the role of environmental predictability in maternal effects and the growth strategy of clonal offspring, a greenhouse experiment was conducted with Glechoma longituba. The parental ramets were arranged in three ultraviolet-B (UV-B) conditions, representing two predictable environments (regular and enhanced UV-B) and an unpredictable environment (random UV-B), respectively. The offspring environments were the same as their parent or not (without UV-B). At the end of experiment, the growth parameters of offspring were analyzed. The results showed that maternal effects and offspring growth were regulated by environmental predictability. Offspring of unpredictable environmental parents invested more resources in improving defense components rather than in rapid growth. Although offspring of predictable parents combined two processes of defense and growth, there were still some differences in the strategies between the two offspring, and the offspring of regular parent increased the biomass allocation to roots (0.069 g of control vs. 0.092 g of regular), but that of enhanced parent changed the resource allocation of nitrogen in roots and phosphorus in blade. Moreover, when UV-B environments of parent and offspring were matched, it seemed that maternal effects were not adaptive, while the growth inhibition in the predictable environment was weaker than that in unpredictable environment. In the predictable environment, the recovered R/S and the increased defense substances (flavonoid and anthocyanin) contributed to improving offspring fitness. In addition, when UV-B environments of parent and offspring were mismatched, offspring growth was restored or improved to some extent. The offspring performance in mismatched environments was controlled by both transgenerational effect and within-generational plasticity. In summary, the maternal effects affected growth strategies of offspring, and the differences of strategies depended on the predictability of parental UV-B environments, the clone improved chemical defense to cope with unpredictable environments, while the growth and defense could be balanced in predictable environments. The anticipatory maternal effects were likely to improve the UV-B resistance.

BackgroundObesity could paradoxically improve prognosis in patients with heart failure (HF), termed the “obesity paradox.” Whether HF etiology could modify the “obesity paradox” is still controversial. In the present study, we aimed to assess the relationship between obesity and death in patients with heart failure with preserved ejection fraction (HFpEF) with non-ischemic versus ischemic etiologies.MethodsWe analyzed 3,360 HFpEF patients from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Cox regression models were used to assess the association of obesity assessed by body mass index (BMI) with short-term and long-term death risk.ResultsOverweight and obesity were associated with a lower risk of long-term all-cause death in patients with non-ischemic HFpEF, even in those with class III obesity (adjusted HR: 0.61, 95% CI 0.38–0.97). However, in the ischemic subgroup, as obesity advanced, this paradoxical relationship was gradually attenuated and disappeared in class III obesity (adjusted HR: 0.93, 95% CI 0.56–1.57). Restricted cubic spline analyses confirmed the differential relationship of baseline BMI with risk of long-term death with a BMI higher than 30 kg/m2 in non-ischemic versus ischemic HFpEF. In the short-term follow-up, the beneficial effects of overweight and obesity on survival were consistently observed in all the BMI categories, with the nadirs of all-cause death risk at class III obesity category both in non-ischemic and ischemic subgroups.Conclusion“Obesity paradox” was evident both in non-ischemic and ischemic HFpEF during short-term follow-up, even in those with class III obesity. However, the beneficial effect of class III obesity disappeared during long-term follow-up in ischemic HFpEF.Clinical Trial Registration[https://clinicaltrials.gov], identifier [NCT00094302].

Background: Lung adenocarcinoma with the classical EGFR 19 deletion and exon 21 L858R point mutations has exhibited good responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. However, the sensitivity of uncommon EGFR exon 20 insertion mutation to third-generation EGFR-TKIs has not been determined. Although emerging targeted therapies for EGFR exon 20 insertion mutation have been reported in recent years, such patients still have a poorer prognosis than those with typical or wild-type EGFR mutations.Case summary: Here, we report the case of a 57-year-old man with advanced non-small cell lung cancer (NSCLC) with a rare EGFR exon 20 N771_P772insH mutation. The patient was treated with furmonertinib as second-line therapy. Although his pleural effusion was more than before that during treatment, various examination results showed that the pleural effusion was closely related to hypoproteinemia; thus, local progression was not considered. His cough was significantly alleviated, and the dose was well tolerated. The patient was evaluated for a remarkable progression-free survival (PFS) of 10.0 months, a duration of response (DOR) of 8.0 months, and an overall survival (OS) of 22.0 months, which had not previously been achieved.Conclusion: The present study indicated that furmonertinib might be a good treatment option for first-line progressive NSCLC patients with EGFR exon 20 insertion mutation.

Background B‐type natriuretic peptide (BNP) is a well‐known biomarker for prognosis in heart failure with patients with preserved ejection fraction. However, the clinical predictive ability of BNP for the risk of stroke in HFpEF is not clear. Methods and Results A total of 799 patients with HFpEF from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial were included. Association of baseline BNP with risk of stroke was assessed using the Cox proportional hazard model. The discriminatory ability of BNP was expressed using the C index. The improvement in 5‐year stroke prediction was assessed by C statistic, categorical net reclassification improvement index, and relative integrated discrimination improvement. A total of 34 (4.3%) patients among the 799 patients with HFpEF experienced stroke events over a median of 2.85 years of follow‐up. The stroke group showed a higher BNP level than the nonstroke group (375 pg/mL versus 241 pg/mL, respectively; P=0.006). Higher BNP levels were associated with increased risk of stroke after multivariable adjustment (hazard ratio, 3.29 [95% CI, 1.51–7.16]) and had a moderate performance for stroke prediction (C index, 0.67). Adding BNP to CHADS2/CHA2DS2‐VASc/R2CHADS2 scores improved their predictive value for stroke (CHADS2: C index, 0.67; BNP+CHADS2: C index, 0.77; net reclassification improvement, 40.9%; integrated discrimination improvement, 3.0%; CHA2DS2‐VASc: C index, 0.64; BNP+CHA2DS2‐VASc: C index, 0.74; net reclassification improvement, 41.4%; integrated discrimination improvement, 2.2%; R2CHADS2: C index, 0.70; BNP+R2CHADS2: C index, 0.78; net reclassification improvement, 40.9%; integrated discrimination improvement, 3.2%). Conclusions BNP is associated with an increased risk of stroke in patients with HFpEF and may be a valuable biomarker for stroke prediction in HFpEF.

The present study investigated the configuration effect of human capital, social capital, and psychological capital on job performance. The human capital questionnaire, social capital scale, psychological capital scale, and job performance scale were used to survey 458 employees. Results revealed that four antecedent configurations could achieve high task performance, and three antecedent configurations can achieve high contextual performance. The high job performance driving path was characterized by “all roads lead to Rome.” Human capital, social capital, and psychological capital affected job performance in the form of configuration, which reflected the asymmetric causal relationship.

Silicon has become the most promising anode material for industrial application to replace the currently utilized graphite because of its large capacity and abundant reserves. However, its poor electronic conductivity and slow Li-ionic diffusion capability along with severe volume expansion impede its high-rate performace. To resolve these issues, we develop a ternary BiSbSi compound with a layered lattice, which presents significantly improved reaction kinetics of 300 mA h g−1 at 20 A g−1 enabled by faster electronic conduction and lithium ion diffusion and simultaneously reduce the volume variation, thus leading to longer cycling stability of remaining 561 mA h g−1 after 1000 cycles at 2 A g−1, compared with Si counterparts. Broadly the ternary layered Si-based anodes hold great promises to be applied in the near future.

At present, the structural changes of extruded materials under thermal-mechanical stress during high-moisture extrusion are still unclear. In this study, the transglutaminase (TG) treatments on the structure of pea protein isolate (PPI) under conditions relevant to high-moisture extrusion processing (50 wt% PPI at 30°C, 120°C and heated to 120°C and subsequently cooled to 30°C) was studied by using a closed cavity rheometer. Strain and frequency sweeping were carried out under various temperature conditions, and the information obtained was drawn into a texture map. Lissajous curves combined with energy dissipation ratio were introduced to characterize the nonlinear response of the samples. The results showed that the storage modulus of PPI increased with the increase of TG concentration during heat treatment. After cooling to 30°C, PPI with 0.25–1%TG could enhance the elasticity, but treating by 2% TG could inhibit the formation of disulfide bonds, the uniform development of the protein network, thus showing the “tough” character. These findings can help to better understand the relationships of material-structure during the extrusion process, and also provide help for further optimization of the quality of meat substitutes.

There are different environmental pressures in coastal and inland wetlands resulting in phenotypic variation among plant populations, which might be related to epigenetic modifications. Phragmites australis is a widespread plant in coastal and inland wetlands, and the phenotype of the population is selected by salinity, but the reasons for the population differences in salt tolerance and phenotype are unclear. We investigated coastal and inland P. australis populations grown under two salinities and two manipulated DNA methylation levels in common gardens. The plants were sprayed with 5-azacytidine (DNA demethylation agent) regularly, and the physiological and morphological traits of reeds were measured. Plant height, density, and basal stem of reeds from different sources were significantly different and correlated with soil conductivity of sampling sites (P < 0.05). Salinity significantly decreased the biomass (37.04%, P < 0.05) and plant height (24.68%, P < 0.05) of inland reeds but had no significant effect on coastal populations (13.48%). P. australis responds to salt stress through phenotypic plasticity, and inland wetland populations exhibit local adaptation to freshwater. Increased salt tolerance in inland populations following DNA demethylation, particularly biomass, plant height, and basal stems (increased 23.62%; 13.08%; 5.35%, respectively), could provide more opportunities in adverse environments. This study will provide important insights into the highly adaptive mechanisms of the large non-model plant.

Background: Prepared rhubarb was obtained by steaming raw rhubarb with wine. Different from raw rhubarb with a purgative effect, prepared rhubarb shows effects of promoting blood circulation and removing blood stasis. However, the mechanisms of its action through regulating endogenous metabolites remain unclear.Purpose: The purpose of this study was to explore active chemical components in prepared rhubarb for its activity on noxious heat blood stasis syndrome (NHBS) by comprehensive metabolomics profiling.Study design: Plant extracts usually show their activities in a synergistic way; therefore, integrated omics was developed as a rational way for a better understanding of their biological effects and potential active compounds.Methods: The activities of prepared rhubarb were evaluated by biochemical and metabolomic analysis; meanwhile, serum chemical profiles were sought using UHPLC-Q-TOF-MS. Gray correlation analysis (GCA) was used for calculating the underlying correlations between them.Results: The metabolomics profiles of rat plasma from model and control groups were significantly different, with 31 endogenous metabolites changed by NHBS. Then, after the administration of prepared rhubarb, 18 of them were regulated. Multiple metabolic pathways were disturbed after NHBS modeling and restored by prepared rhubarb, among which had a greater impact on sphingolipid metabolism. A total of 28 compounds from prepared rhubarb absorbed into the plasma were identified, including nine prototypes and 19 metabolites. Statistical results suggested that rhein and its metabolites accounted for half of the top 10 active compounds in prepared rhubarb for its biomedical activities.Conclusion: This study presented evidence for the therapeutic effects and active chemicals of prepared rhubarb on NHBS in the way of metabolomics.

As an intestinal organism settled long-term within the gut of marine fish, Vibrio scophthalmi is a potential object for the bacterium genetic variation and adaptation research. The genetic diversity, antimicrobial resistance phenotype, and genotype of 33 V. scophthalmi isolated from diseased marine fish intestines between 2002 and 2020 were evaluated. The results showed that all isolates were frequently resistant to penicillins, cephalosporins, aminoglycosides, and macrolides and displayed multidrug-resistant (MDR) phenotype in vitro. Thirty percent of isolates were resistant to more than 20 different drugs. The average insensitive (resistant and intermediate) rate of V. scophthalmi isolates was 49.5%~81.8% between 2002 and 2020, but the t-test revealed that there was no significant difference in the drug-resistance rate of V. scophthalmi isolates with typical interannual variability. Eleven antimicrobial resistance genes (strB, strA, ant(3 ˝)-I, mphA, blaPSE, qnrS, tetC, tetE, tetM, tetS, and int1) were detected in these isolates, but the antimicrobial resistance phenotypes and genotypes of these isolates were not consistent. Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) analysis indicated that 33 isolates could be divided into two clusters (G1 and G3) and two single isolates (G2 and G4), and the G2 cluster was isolated from South Sea C. undulates with typical geographical species differences. There was no significant correlation between the drug susceptibility and the genetic types of V. scophthalmi isolates. The results reveal the mismatch phenomenon between antimicrobial resistance and genotype of inherent V. scophthalmi in the marine fish intestines, and the antimicrobial susceptibility isolates might be a potential risk source for storage and transmission of resistance genes.

BackgroundSeveral published studies have examined the association of coffee consumption with atrial fibrillation (AF) risk, but their findings are still controversial. Therefore, we performed a systematic review and dose–response meta-analysis of prospective studies to determine the relationship between coffee consumption and the risk of incident AF.MethodsWe systematically retrieved the PubMed and Embase databases until October 2021 for pertinent studies that reported the association of coffee consumption (caffeinated or decaffeinated coffee) with AF risk. A cubic spline random-effects model was used to fit the potential dose–response curve. The effect estimates were expressed as adjusted risk ratios (RRs) and 95% CIs.ResultsA total of 10 prospective studies (11 cohorts) involving 30,169 AF events and 723,825 participants were included. In the dose–response analysis, there was a linear inverse association between coffee intake and risk of AF although not statistically significant (Pnon–linearity = 0.25). Compared with participants with no coffee consumption, the RRs (95% CI) of AF risk estimated directly from the dose–response curve were 1.01 (0.98–1.03), 1.00 (0.97–1.04), 0.99 (0.92–1.02), 0.95 (0.89–1.01), 0.94 (0.87–1.01), 0.89 (0.79–1.02), and 0.87 (0.76–1.02) for 1–7 cups of coffee per day, respectively. One cup per day increased in coffee consumption was associated with a 2% reduced risk of AF (RR = 0.98, 95% CI: 0.97–1.00, P = 0.02).ConclusionsOur evidence from this meta-analysis suggested that coffee consumption had a trend toward reducing the risk of AF in a dose–response manner. Further studies could be conducted to reinforce our findings.

As one of the most important enteric viruses, sapovirus (SaV) can infect humans and a variety of animals. Until now, 19 SaV genogroups have been identified, among which 4 from human (GI, GII, GIV, and GV) and 8 from swine (GIII, GV–GXI). Porcine sapovirus (PoSaV) GIII has been prevalent in China; however, the status of PoSaV infection in Yunnan province remains unknown. In this study, 202 fecal samples were collected from piglets associated with outbreaks of acute diarrhea in Yunnan between January and May 2020. PoSaV detection revealed that the total PoSaV infection rate in Yunnan was 35.2%, with 21 PoSaV strains determined and phylogenetically analyzed. The phylogenetic tree analyses demonstrated that twenty PoSaV strains belonged to GIII and fell into five genotypes, whereas one PoSaV strain (YNQB) belonged to GV. Sequence alignments revealed deletions in VP2 region in 10 of the 20 GIII strains, as well as deletions and insertions in VP1 region of the GV strain (YNQB). Furthermore, genomic recombination analyses showed that two GIII strains (YNAN and YNJD) were recombinants, closely related to reference sequences MK965898 and LC215880, MK965898 and FJ387164, respectively. In summary, PoSaV-GIII strains were identified in Yunnan in 2020, and for the first time, a PoSaV-GV strain was identified from China, whereas the comprehensive analyses illustrated high genetic diversity of Yunnan PoSaV strains. This study may shed new light on the current PoSaV infections in Yunnan and pave the way toward further control of the PoSaV infections in China.

BackgroundPapillary thyroid cancer (PTC) is the most common thyroid tumor, and early diagnosis and treatment can effectively improve prognosis. Many controversies surround the treatment method of T1N0M0 PTC. Recently, thermal ablation (TA) has shown some benefits in the treatment of PTC patients, but the safety and efficacy of its treatment remain controversial. This article performs a meta-analysis of TA in patients with T1aN0M0 and T1bN0M0 PTC.MethodsThe PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for retrospective or prospective studies of TA for treating patients with T1N0M0 PTC from the database establishment to May 1, 2022. Data on volume reduction rate (VRR), disease progress, and complication rate were collected. In addition, a meta-analysis was performed using the Stata 12.0 and Review Manager 5.3.ResultsA total of 9 eligible studies were included. Our study demonstrated the effectiveness of VRR and disease progress. The VRR was reduced after 3 months (−75.90%; 95% CI [−118.46–33.34%]), 6 months (34.33%; 95% CI [15.01–53.65%]), 12 months (78.69%; 95% CI [71.69–85.68%]), and 24 months (89.97%; 95% CI [84.00–95.94%]). The disease progress was 1.9% (95% CI [1.1–3.0]). Safety is justified by the complication rate, which was 6.5% (95% CI [3.5–10.2]). Pain and hoarseness were the most common complications, and no life-threatening complications were reported. Egger’s test demonstrated that publication bias was acceptable.ConclusionsTA is an effective and safe method for managing T1aN0M0 and T1bN0M0 papillary thyroid nodules.

Biogeography (body site) is known to be one of the main factors influencing the composition of the skin microbial community. However, site-associated microbial variability at a fine-scale level was not well-characterized since there was a lack of high-resolution recognition of facial microbiota across kingdoms by shotgun metagenomic sequencing. To investigate the explicit microbial variance in the human face, 822 shotgun metagenomic sequencing data from Han Chinese recently published by our group, in combination with 97 North American samples from NIH Human Microbiome Project (HMP), were reassessed. Metagenomic profiling of bacteria, fungi, and bacteriophages, as well as enriched function modules from three facial sites (forehead, cheek, and the back of the nose), was analyzed. The results revealed that skin microbial features were more alike in the forehead and cheek while varied from the back of the nose in terms of taxonomy and functionality. Analysis based on biogeographic theories suggested that neutral drift with niche selection from the host could possibly give rise to the variations. Of note, the abundance of porphyrin-producing species, i.e., Cutibacterium acnes, Cutibacterium avidum, Cutibacterium granulosum, and Cutibacterium namnetense, was all the highest in the back of the nose compared with the forehead/cheek, which was consistent with the highest porphyrin level on the nose in our population. Sequentially, the site-associated microbiome variance was confirmed in American populations; however, it was not entirely consistent. Furthermore, our data revealed correlation patterns between Propionibacterium acnes bacteriophages with genus Cutibacterium at different facial sites in both populations; however, C. acnes exhibited a distinct correlation with P. acnes bacteriophages in Americans/Chinese. Taken together, in this study, we explored the fine-scale facial site-associated changes in the skin microbiome and provided insight into the ecological processes underlying facial microbial variations.

ObjectiveTo further understand the influence of regional and ethnic factors on blood routine indicators.MethodsThe routine blood test (RBT) results of 617 healthy men aged 18–45 years old of the Li, Tibet, and Han nationalities living in the city of Sanya, Hainan Province (200 m), the city of Xining, Qinghai Province (2,300 m), and Maduo County of Qinghai Province (4,300 m) for a long time were studied. Eight indexes, such as the red blood cell (RBC), hemoglobin (Hb), and platelet (PLT) counts, were compared and analyzed.ResultsWith an increase in altitude, the RBT index values and change trends of the different ethnic groups were different. When the altitude increased by 2,000 m, the RBC and Hb increased by 6.6 and 8.1%, respectively, and the PLT decreased by 16.8%. However, the RBC, Hb, and PLT of the Tibetan subjects decreased by 7.4, 5.1, and 3.0%, respectively. In the same region, there were also significant differences in the RBT index values among the ethnic groups. The RBC increased, Hb decreased, and PLT did not change in the Li nationality in Sanya compared with the Han nationality. The RBC, Hb, and PLT of Tibetans in the Xining area were significantly higher than those of the Han population. Referring to the current RBT reference value range in China, the abnormal rates of the various RBT index values of the enrolled population were high. By utilizing Hb as an example, 27.7% of the Li nationality in Sanya was low, 67.0% of the Tibetan nationality in Xining was high, and 89.4% of the Maduo Han nationality was high. The PLT was lower in the Sanya Li nationality (13.8%) and the Maduo Han nationality (88.3%).ConclusionRegional and ethnic factors have a significant impact on the RBT, and the current range of normal values of the RBT in China needs to be revised and adjusted.

ObjectiveLarge body of studies described individuals with obesity experiencing a worse prognosis in COVID-19. However, the effects of obesity on the prognosis of COVID-19 in patients without comorbidities have not been studied. Therefore, the current study aimed to provide evidence of the relationship between obesity and clinical outcomes in COVID-19 patients without comorbidities.MethodsA total of 116 hospitalized COVID-19 patients without comorbidities from the ORCHID study (Patients with COVID-19 from the Outcomes Related to COVID-19 Treated with Hydroxychloroquine among Inpatients with Symptomatic Disease) were included. Obesity is defined as a BMI of ≥30 kg/m2. A Cox regression analysis was used to estimate the hazard ratio (HR) for discharge and death after 28 days.ResultsThe percentage of obesity in COVID-19 patients without comorbidities was 54.3% (63/116). Discharge at 28 days occurred in 56/63 (84.2%) obese and 51/53 (92.2%) non-obese COVID-19 patients without comorbidities. Four (3.4%) COVID-19 patients without any comorbidities died within 28 days, among whom 2/63 (3.2%) were obese and 2/53 (3.8%) were non-obese. Multivariate Cox regression analyses showed that obesity was independently associated with a decreased rate of 28-day discharge (adjusted HR: 0.55, 95% CI: 0.35–0.83) but was not significantly associated with 28-day death (adjusted HR: 0.94, 95% CI: 0.18–7.06) in COVID-19 patients without any comorbidities.ConclusionsObesity was independently linked to prolonged hospital length of stay in COVID-19 without any comorbidity. Larger prospective trials are required to assess the role of obesity in COVID-19 related deaths.

Summary: We demonstrate the successful implementation of a terahertz (THz) quantum-well photodetector (QWP) for effective signal collection in a scattering-type scanning near-field optical microscope (s-SNOM) system. The light source is an electrically pumped THz quantum cascade laser (QCL) at 4.2 THz, which spectrally matches with the peak photoresponse of THz QWP. The sensitive THz QWP has a low noise equivalent power (NEP) of about 1.1 pW/Hz0.5 and a spectral response range from 2 to 7 THz. The fast-responding capability of the THz QWP is vital for detecting the rapidly tip-modulated THz light which can effectively suppress the background noise. The THz images of the nanostructure demonstrate a spatial resolution of about 95 nm, corresponding to ∼λ/752 at 4.2 THz. We experimentally investigate and theoretically interpret the formation of the fringes which appear at the edge position of a gold stripe in the THz near-field image.

The 21st Conference of the Parties (COP 21) was a significant attempt by governments to make and monitor commitments to limit global warming. However, COP 23 “sought to continue the global momentum to decouple output from greenhouse gas (GHG) emissions.” Among the GHGs, carbon dioxide (CO2) is the major one most countries worry about. This paper examines the decoupling situations of China’s CO2 emissions and economic growth, considering the country’s progress situation from the year 2000 to 2019. For this, we employed two models: the environmental Kuznets curve (EKC) model for exploring the long-run decoupling status and the influence factors of CO2 emissions and the Tapio model for the short-run decoupling status. Later, the Tapio model was extended to analyze the influence of industrial structure, energy structure, and population structure. The long-term results suggest that China’s CO2 emissions have not decoupled yet, but the emission’s intensity has decoupled in mid-2006. The short-term decoupling results revealed that the degree of decoupling changed to weak from strong in the last five years. According to the influencing structure’s results, the industrial and energy structures inhibited CO2 emissions, but their influence was not strong enough to offset the impact of economic growth; however, the population structure indorsed CO2 emissions. Lastly, we found an unusual verdict that is the change of EKC into a U-shape from an inverted U-shape, and the observed reason is the control variable introduction. We also observed that the turning point became greater after introducing the industrial structure separately. Overall, from the perspective of the observed decoupling trends, it is suggested that China should strengthen and further optimize its energy structure to match the industrial structure.

Water is the source of life and the fundamental element of ecology, and climate is inseparable from water. To evaluate the influence of water-adaptive space in a traditional Weizi (polder village) settlement on its microclimate, the authors analyzed the morphological characteristics of such a polder village and applied the ENVI-met model to simulate the impact of water bodies and village morphological elements on human thermal comfort. This paper demonstrates the positive impact of water bodies on improving the thermal environment of a village and regulating its microclimate by quantifying the impact of morphological elements of the settlement on microclimate. The results indicate that: 1) The simulation model fits the actual measurements well, and the simulation accurately reflects experimental results; 2) In summer, the cooling effect of water bodies is better in the afternoon than in the morning, especially from 12:00 to 15:00. The cooling effect is significantly correlated with the distance to water bodies, i.e., the closer, the better; 3) Building density and man-made underlying surface are negatively correlated with temperature, humidity, and Physiological Equivalent Temperature value, while greening rate and water body rate are positively correlated with microclimate. Overall, water bodies can improve outdoor comfort in summer and thus should be protected and developed in rural planning and design. Villages can be built around water bodies for a maximized cooling effect, and microclimate comfort can be effectively improved by increasing green plants near the village center, and reducing man-made underlying surface and building density. The results of this study will guide the improvement of the habitat environment in the process of rural revitalization, as well as the protection and re-development of traditional villages.

Alkenes and their related analogs are ideal starting materials for organic synthesis, and the selective difunctionalization of alkenes, which allows the simultaneous introduction of two neighboring bonds, has gained considerable attention in recent years. In particular, the photoredox-catalyzed difunctionalization of alkenes has also been accomplished, which has been regarded as an increasingly powerful tool for the synthesis of miscellaneous interesting molecular scaffolds in an environmentally benign and economical manner. Several exquisite strategies have been developed to facilitate this transformation, such as photosensitizer-catalyzed redox reactions, electron donor-acceptor (EDA) complexes-mediated photoreactions, and atom transfer radical addition (ATRA) reactions. This literature review briefly describes the most recent key progress on the photoredox-catalyzed 1,2-difunctionalization of various structurally diverse alkenes, including 1,2-dicarbofunctionalization, 1,2-carboheterofunctionalization, and 1,2-diheterofunctionalization, with a special emphasis on the mechanistic details.

In recent years, edge-based intelligent UAV delivery systems have attracted significant interest from both the academic and industrial sectors. One key obstacle faced by these smart UAV delivery systems is data privacy, as they rely on vast amounts of data from users and UAVs for training machine learning models for person re-identification (ReID) purposes. To tackle this issue, federated learning (FL) has been extensively adopted as a promising solution since it only involves sharing and updating model parameters with a central server, without transferring raw data. However, traditional FL still suffers from the problem of having a single point of failure. In this study, we present a performance optimization method for federated person re-identification using benchmark analysis in blockchain-powered edge-based smart UAV delivery systems. Our method integrates a decentralized FL mechanism enabled by blockchain, which eliminates the necessity for a central server and stores private data on a decentralized permissioned blockchain, thus preventing a single point of failure. We employ the person ReID application in intelligent UAV delivery systems as a representative example to drive our research and examine privacy concerns. Additionally, we introduce the Federated Re-identification Consensus (FRC) protocol to address the scalability issue of the blockchain in supporting UAV delivery systems. The efficiency of our proposed method is illustrated through experiments on energy efficiency, confirmation time, and throughput. We also explore the effects of the incentive mechanism and analyze the system’s resilience under various security attacks. This study offers valuable insights and potential solutions for addressing data privacy and security challenges in the fast-growing domain of smart UAV delivery systems.

The study aims to explore the medical prospect of melatonin (MLT) and the underlying therapeutic mechanism of MLT-mediated macrophage (Mφ) polarization on the function of nucleus pulposus (NP) in intervertebral disc degeneration (IDD). RAW 264.7 Mφs were induced by lipopolysaccharide (LPS) to simulate Mφ polarization and the inflammatory reaction of Mφs with or without MLT were detected. Conditioned medium (CM) collected from these activated Mφs with or without MLT treatment were further used to incubate NP cells. The oxidative stress, inflammation and extracellular matrix (ECM) metabolism in NP cells were determined. Then, the changes in SIRT1/Notch signaling were detected. The agonist (SRT1720) and inhibitor (EX527) of SIRT1 were used to further explore the association among MLT. The interaction between SIRT1 and NICD was detected by immunoprecipitation (IP). Finally, puncture-induced rat IDD models were established and IDD degrees were clarified by X-ray, MRI, H&E staining and immunofluorescence (IF). The results of flow cytometry and inflammation detection indicated that LPS could induce M1-type Mφ polarization with pro-inflammatory properties. MLT significantly inhibited the aforementioned process and inhibited M1-type Mφ polarization, accompanied by the alleviation of inflammation. Compared with those without MLT, the levels of oxidative stress, pro-inflammatory cytokines and ECM catabolism in NP cells exposed to CM with MLT were markedly downregulated in a dose-dependent manner. The inhibition of SIRT1 and the enhancement of Notch were observed in activated Mφs and they can be reversed after MLT treatment. This prediction was further confirmed by using the SRT1720 and EX527 to activate or inhibit the signaling. The interaction between SIRT1 and NICD was verified by IP. In vivo study, the results of MRI, Pfirrmann grade scores and H&E staining demonstrated the degree of disc degeneration was significantly lower in the MLT-treated groups when compared with the IDD control group. The IF data showed M1-type Mφ polarization decreased after MLT treatment. MLT could inhibit M1-type Mφ polarization and ameliorate the NP cell injury caused by inflammation in vitro and vivo, which is of great significance for the remission of IDD. The SIRT1/Notch signaling pathway is a promising target for MLT to mediate Mφ polarization.

Purpose: The accurate preoperative histopathological grade diagnosis of adult gliomas is of great significance for the formulation of a surgical plan and the implementation of a subsequent treatment. The aim of this study is to establish a predictive model for classifying adult gliomas into grades 2–4 based on preoperative conventional multimodal MRI radiomics. Patients and Methods: Patients with pathologically confirmed gliomas at Huashan Hospital, Fudan University, between February 2017 and July 2019 were retrospectively analyzed. Two regions of interest (ROIs), called the maximum anomaly region (ROI1) and the tumor region (ROI2), were delineated on the patients’ preoperative MRIs utilizing the tool ITK-SNAP, and Pyradiomics 3.0 was applied to execute feature extraction. Feature selection was performed utilizing a least absolute shrinkage and selection operator (LASSO) filter. Six classifiers, including Gaussian naive Bayes (GNB), random forest (RF), K-nearest neighbor (KNN), support vector machine (SVM) with a linear kernel, adaptive boosting (AB), and multilayer perceptron (MLP) were used to establish predictive models, and the predictive performance of the six classifiers was evaluated through five-fold cross-validation. The performance of the predictive models was evaluated using the AUC and other metrics. After that, the model with the best predictive performance was tested using the external data from The Cancer Imaging Archive (TCIA). Results: According to the inclusion and exclusion criteria, 240 patients with gliomas were identified for inclusion in the study, including 106 grade 2, 68 grade 3, and 66 grade 4 gliomas. A total of 150 features was selected, and the MLP classifier had the best predictive performance among the six classifiers based on T2-FLAIR (mean AUC of 0.80 ± 0.07). The SVM classifier had the best predictive performance among the six classifiers based on DWI (mean AUC of 0.84 ± 0.05); the SVM classifier had the best predictive performance among the six classifiers based on CE-T1WI (mean AUC of 0.85 ± 0.06). Among the six classifiers, based on ROI1, the MLP classifier had the best prediction performance (mean AUC of 0.78 ± 0.07); among the six classifiers, based on ROI2, the SVM classifier had the best prediction performance (mean AUC of 0.82 ± 0.07). Among the six classifiers, based on the multimodal MRI of all the ROIs, the SVM classifier had the best prediction performance (average AUC of 0.85 ± 0.04). The SVM classifier, based on the multimodal MRI of all the ROIs, achieved an AUC of 0.81 using the external data from TCIA. Conclusions: The prediction model, based on preoperative conventional multimodal MRI radiomics, established in this study can conveniently, accurately, and noninvasively classify adult gliomas into grades 2–4, providing certain assistance for the precise diagnosis and treatment of patients and optimizing their clinical management.

Ti4+-ion-doped (n + 1)SrO − nCeO2 (n = 2) ceramic systems were prepared with the conventional solid-state reaction method, and the effects of the phase structures and compositions, sintering behaviors, microstructures and microwave dielectric properties of these ceramic systems were investigated in detail as a function of TiO2 content. The analytical results of the XRD patterns show that the pure (n + 1)SrO − nCeO2 (n = 2) system is a composite-phase ceramic system with coexisting SrCeO3 and Sr2CeO4 phases (represented as a SrCeO3 + Sr2CeO4 system), which belong to the orthogonal structures of the Pmcn (62) and Pbam (55) space groups, respectively. For the xTiO2-(1 − x) (SrCeO3 + Sr2CeO4) (x = 0.1–0.4) ceramic samples, the secondary phase Sr2TiO4 can also be detected within the range of the investigated components. Meanwhile, the Raman spectroscopy, SEM-EDS, and HRTEM (SAED) analysis results also verified the correctness and consistency of the phase structures and compositions for all the given specimens. In addition, complex impedance spectroscopy was used to detect the conductive behavior of these compound ceramic systems, and the calculation results show that the appropriate addition of Ti4+-ions can make the SrCeO3 + Sr2CeO4 system have better thermal stability. The composition of x = 0.2 multiphase structural ceramic sample sintered at 1330 °C for 4 h has a near zero τf value of ~−4.6 ppm/°C, a moderate εr of ~40.3 and a higher Q × f~44,020 GHz (at 6.56 GHz). The relatively superior-performing ceramics developed in this work are expected to provide a promising microwave dielectric material for communication components.

Metastasis, particularly brain metastasis, continues to puzzle researchers to this day, and exploring its molecular basis promises to break ground in developing new strategies for combatting this deadly cancer. In recent years, the research focus has shifted toward the earliest steps in the formation of metastasis. In this regard, significant progress has been achieved in understanding how the primary tumor affects distant organ sites before the arrival of tumor cells. The term pre-metastatic niche was introduced for this concept and encompasses all influences on sites of future metastases, ranging from immunological modulation and ECM remodeling to the softening of the blood–brain barrier. The mechanisms governing the spread of metastasis to the brain remain elusive. However, we begin to understand these processes by looking at the earliest steps in the formation of metastasis. This review aims to present recent findings on the brain pre-metastatic niche and to discuss existing and emerging methods to further explore the field. We begin by giving an overview of the pre-metastatic and metastatic niches in general before focusing on their manifestations in the brain. To conclude, we reflect on the methods usually employed in this field of research and discuss novel approaches in imaging and sequencing.

WTe2, a low-symmetry transition metal dichalcogenide, has broad prospects in functional device applications due to its excellent physical properties. When WTe2 flake is integrated into practical device structures, its anisotropic thermal transport could be affected greatly by the substrate, which matters a lot to the energy efficiency and functional performance of the device. To investigate the effect of SiO2/Si substrate, we carried out a comparative Raman thermometry study on a 50 nm-thick supported WTe2 flake (with κzigzag = 62.17 W·m−1·K−1 and κarmchair = 32.93 W·m−1·K−1), and a suspended WTe2 flake of similar thickness (with κzigzag = 4.45 W·m−1·K−1, κarmchair = 4.10 W·m−1·K−1). The results show that the thermal anisotropy ratio of supported WTe2 flake (κzigzag/κarmchair ≈ 1.89) is about 1.7 times that of suspended WTe2 flake (κzigzag/κarmchair ≈ 1.09). Based on the low symmetry nature of the WTe2 structure, it is speculated that the factors contributing to thermal conductivity (mechanical properties and anisotropic low-frequency phonons) may have affected the thermal conductivity of WTe2 flake in an uneven manner when supported on a substrate. Our findings could contribute to the 2D anisotropy physics and thermal transport study of functional devices based on WTe2 and other low-symmetry materials, which helps solve the heat dissipation problem and optimize thermal/thermoelectric performance for practical electronic devices.

Newcastle disease (ND) and infectious bursal disease (IBD) are two key infectious diseases that significantly threaten the health of the poultry industry. Although existing vaccinations can effectively prevent and treat these two diseases through multiple immunizations, frequent immunization stresses significantly impact chicken growth. In this study, three recombinant adenoviruses, rAd5-F expressing the NDV (genotype VII) F protein, rAd5-VP2 expressing the IBDV VP2 protein, and rAd5-VP2-F2A-F co-expressing F and VP2 proteins, were constructed using the AdEasy system. The F and VP2 genes of the recombinant adenoviruses could be transcribed and expressed normally in HEK293A cells as verified by RT-PCR and Western blot. The three recombinant viruses were shown to have similar growth kinetics as rAd5-EGFP. Compared with the PBS and rAd5-EGFP groups, SPF chickens immunized with recombinant adenoviruses produced higher antibody levels, more significant lymphocyte proliferation, and significantly higher CD4+/CD3+ and CD8+/CD3+ cells in peripheral blood. The survival rate of SPF chickens immunized with rAd5-F and rAd5-VP2-F2A-F after the challenge with DHN3 was 100%, and 86% of SPF chickens showed no viral shedding at 7 dpc. The survival rate of SPF chickens immunized with rAd5-VP2 and rAd5-VP2-F2A-F after the challenge with BC6/85 was 86%. rAd5-VP2 and rAd5-VP2-F2A-F significantly inhibited bursal atrophy and pathological changes compared to the rAd5-EGFP and PBS groups. This study provides evidence that these recombinant adenoviruses have the potential to be developed into safe and effective vaccine candidates for the prevention and control of ND and IBD.

Taraxacum kok-saghyz Rodin (TKS) has great potential as an alternative natural-rubber (NR)-producing crop. The germplasm innovation of TKS still faces great challenges due to its self-incompatibility. Carbon-ion beam (CIB) irradiation is a powerful and non-species-specific physical method for mutation creation. Thus far, the CIB has not been utilized in TKS. To better inform future mutation breeding for TKS by the CIB and provide a basis for dose-selection, adventitious buds, which not only can avoid high levels of heterozygosity, but also further improve breeding efficiency, were irradiated here, and the dynamic changes of the growth and physiologic parameters, as well as gene expression pattern were profiled, comprehensively. The results showed that the CIB (5–40 Gy) caused significant biological effects on TKS, exhibiting inhibitory effects on the fresh weight and the number of regenerated buds and roots. Then,15 Gy was chosen for further study after comprehensive consideration. CIB-15 Gy resulted in significant oxidative damages (hydroxyl radical (OH•) generation activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and malondialdehyde (MDA) content) and activated the antioxidant system (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX)) of TKS. Based on RNA-seq analysis, the number of differentially expressed genes (DEGs) peaked at 2 h after CIB irradiation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DNA-replication-/repair- (mainly up-regulated), cell-death- (mainly up-regulated), plant-hormone- (auxin and cytokinin, which are related to plant morphogenesis, were mainly down-regulated), and photosynthesis- (mainly down-regulated) related pathways were involved in the response to the CIB. Furthermore, CIB irradiation can also up-regulate the genes involved in NR metabolism, which provides an alternative strategy to elevate the NR production in TKS in the future. These findings are helpful to understand the radiation response mechanism and further guide the future mutation breeding for TKS by the CIB.