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Government often acts as the largest buyer in an economy through government procurement. The allocation of procurement orders however is often distorted. We build a model with heterogeneous firms endogenously seeking government favors in procurement to show that misallocation of procurement orders further leads to misallocation of production factors. Using the enactment of the in 2003 as a natural experiment, we find that tighter regulation of procurement in China lowers the extent of resource misallocation in industries that rely more on government procurement. We further provide firm-level evidence in support of our model. [ABSTRACT FROM AUTHOR]

The metal-catalyzed dehydrogenation of alcohols without any oxidant or additive has been demonstrated as an atom-economic and environmentally friendly strategy for carboxylic acid synthesis. Among the various catalysts applied to this transformation, Ru-based homogeneous ones have been the most extensively studied owing to their remarkable catalytic activity. However, these catalysts required multiple complicated synthesis steps. In addition, they were either difficult to recycle or their recovery processes were relatively tedious. Therefore, a series of Ru-containing heterogeneous catalysts with zeolitic imidazolium frameworks (ZIFs)-derived materials were designed and fabricated. A thorough screening of various parameters was conducted, and it was found that the material obtained by loading a Ru concentration of 0.05 mol/L into Co species embedded in porous N-doped carbon (Ru0.05@Co-NC) had the best catalytic performance in this transformation, affording a handful of carboxylic acid products from the corresponding aromatic or aliphatic alcohols in moderate to high yields. Additionally, the catalyst showed remarkable recyclability as it could be recycled eight times with stable activity fluctuation (45–52%). It is noteworthy that catalyst recycling was convenient and fast, which could be realized simply by an external magnet. Moreover, the stable morphology and structure of Ru0.05@Co-NC, along with its high specific surface area, hierarchical pore structure, high porosity, and other properties, jointly contributed to its high catalytic activity and good recyclability. Furthermore, the stability and activity of Ru0.05@Co-NC were further evaluated through acid etching experiments, which revealed that some Ru species could stably exist in concentrated acids and play a pivotal role in promoting this catalytic process. [ABSTRACT FROM AUTHOR]

• G661R mutation of ADAMTS10 causing glaucoma introduced in mice using CRISPR/Cas9. • ADAMTS10 is expressed along optic nerve axons and in retinal ganglion cells. • ADAMTS10 is not colocalized with fibrillin microfibrils in retina and optic nerve. • ADAMTS10 could function independent of fibrillin. • ADAMTS10 regulates transforming growth factor beta signaling in developing retina. Glaucoma is a neurodegenerative disease that causes irreversible blindness due to loss of retinal ganglion cells (RGCs) and their axons. We previously identified a G661R mutation of ADAMTS10 (A Disintegrin And Metalloproteinase with ThromboSpondin type 1 motif 10) as the disease-causing mutation in a beagle model of glaucoma. ADAMTS10 is a secreted matrix metalloproteinase that belongs to the ADAMTS family which is involved in extracellular matrix (ECM) turnover. Previous studies have shown that ADAMTS10 binds fibrillin microfibrils, promotes their formation, and influences their fibrillin isoform composition. Here, we established a mouse model carrying the G661R mutation of ADAMTS10 (ADAMTS10G661R/G661R) to investigate its ocular phenotypes related to glaucoma and to explore possible functions of ADAMTS10. We found that ADAMTS10 was expressed in the inner retina and along RGC axons in the optic nerve. However, ADAMTS10 was not colocalized with fibrillin microfibrils in these tissues, suggesting fibrillin-independent function for ADAMTS10. In electroretinogram experiments, we found that ADAMTS10G661R/G661R mice had reduced amplitude of retinal responses to dim light stimulus, indicating RGC dysfunction. The reduced RGC function coincided with RGC axon structural changes manifested as smaller optic nerves and fewer optic nerve axons, which may contribute to glaucoma. The reduced number of optic nerve axons found for ADAMTS10G661R/G661R mice occurred early, suggesting developmental deficits. Subsequent experiments found increased apoptosis in the retina of ADAMTS10G661R/G661R mice during postnatal development, which could result in fewer RGCs produced, accounting for fewer optic nerve axons in adulthood. Consistent with a protective effect of transforming growth factor β (TGFβ) signaling against apoptosis during retinal development as shown previously by others, we found increased apoptosis accompanied by decreased TGFβ signaling in the developing retina of ADAMTS10G661R/G661R mice, suggesting a novel role for ADAMTS10 in regulating TGFβ signaling which could involve direct interaction between ADAMTS10 and latent TGFβ. [ABSTRACT FROM AUTHOR]

• Structural change increases the skill premium if the sector absorbing more labor is skill-intensive and decreases the skill premium otherwise. • Capital deepening and sectoral productivity growth may change the skill premium by driving structural change. • Variations in the skill premium along the process of structural change depend on sectoral differences in factor-augmenting technologies, capital-labor substitutability and factor intensity. • Within-sector labor-augmenting technological change significantly influences the skill premium through the mechanism of structural change in the U.S. economy. Unlike existing studies that highlight the role of directed technological change in causing variations in the skill premium, we argue that capital deepening and sectoral productivity growth—even when neither skill-biased nor unskilled-biased—may change the skill premium by driving structural change. Using a standard model of structural change with sectoral differences in factor-augmenting technologies, capital-labor substitutability and factor intensity, we show that a larger fraction of skilled labor may be reallocated to the less capital-intensive sector or the less flexible sector as the capital-labor ratio increases. The process may increase the skill premium if the sector absorbing more labor is skill-intensive and deceases the skill premium otherwise. Capital-augmenting or labor-augmenting technological change within a sector may also cause such changes, even when it is not skill-biased or unskilled-biased. We apply the model to the U.S. economy over the period 1977-2005. While the effects of capital deepening and within-sector capital-augmenting technological change are limited, within-sector labor-augmenting technological change significantly influences the skill premium through the mechanism of structural change. We find that without labor-augmenting technological change in the goods-producing sector, the skill premium decreases by about one quarter because the share of the services sector that is more skill-intensive than the goods-producing sector falls by more than half. [ABSTRACT FROM AUTHOR]

Though widely used to assess pathological scars, the modified Vancouver Scar Scale (mVSS) is neither convenient nor objective. Shear wave elastography (SWE) is used to evaluate the stiffness of pathological scars. We aimed to determine the correlation between mVSS score and elastic modulus (EM) measured by SWE for pathological scars. Clinical information including ultrasound (US) results of the enrolled patients with pathological scars was analyzed. The clinical severity of the pathological scars was evaluated by mVSS. Skin stiffness, as represented by EM, was calculated using SWE. The average EM of the whole scar (EMWHOLE), hardest part of the scar (EMHARDEST), and normal appearance of the skin around the scar (EMNORMAL) were also recorded. Enrolled in this study were 69 pathological scars, including 28 hypertrophic scars and 41 keloids. The univariable regression analyses showed that the EM of pathological scars was closely related to mVSS score, while the linear multivariable regression analyses showed no significantly correlation. Curve fitting and threshold effect analysis revealed that when EMWHOLE was less than 166.6 kPa or EMHARDEST was less than 133.07 kPa, EM was positively correlated with mVSS score. In stratified analysis, there was no significant linear correlation and threshold effect between EMWHOLE and mVSS score in hypertrophic scars or keloids. However, the fully adjusted smooth curves presented a linear association between mVSS score and EMHARDEST in keloids (the adjusted β [95% CI] was 0.010 [0.001, 0.018]), but a threshold and nonlinear association were found in hypertrophic scars. When EMHARDEST was less than 156.13 kPa, the mVSS score increased along with the hardest scar part stiffness; the adjusted β (95% CI) was 0.024 (0.009, 0.038). In conclusion, EM of pathological scars measured by SWE were correlated with mVSS within a threshold range, and showed different association patterns in hypertrophic scars and keloids. [ABSTRACT FROM AUTHOR]

Triple negative (TN) breast cancer is a subtype of breast cancer which is difficult for early detection and the prognosis is poor. In this paper, 910 benign and 934 malignant (110 TN and 824 NTN) B-mode breast ultrasound images were collected. A Resnet50 deep convolutional neural network was fine-tuned. The results showed that the averaged area under the receiver operating characteristic curve (AUC) of discriminating malignant from benign ones were 0.9789 (benign vs. TN), 0.9689 (benign vs. NTN). To discriminate TN from NTN breast cancer, the AUC was 0.9000, the accuracy was 88.89%, the sensitivity was 87.5%, and the specificity was 90.00%. It showed that the computer-aided system based on DCNN is expected to be a promising noninvasive clinical tool for ultrasound diagnosis of TN breast cancer. [ABSTRACT FROM AUTHOR]

To explore the predictive value of radiomics nomogram using pretreatment ultrasound for disease-free survival (DFS) after resection of triple negative breast cancer (TNBC). A total of 486 TNBC patients from 3 different institutions were consecutively recruited for this study. They were categorized into the primary cohort (n = 216), as well as the internal validation cohort (n = 108) and external validation cohort (n = 162). In primary cohort, least absolute shrinkage and selection operator logistic regression algorithm was used to select recurrence-related radiomics features extracted from the breast tumor and peritumor regions, and a radiomics signature was constructed derived from the grayscale ultrasound images. A radiomic nomogram integrating independent clinicopathological variables and radiomic signature was established with uni- and multivariate cox regressions. The predictive nomogram was validated using an internal cohort and an independent external cohort regarding abilities of discrimination, calibration and clinical usefulness. The patients with higher Rad-score had a worse prognostic outcome than those with lower Rad-score in primary cohort and two validation cohorts (All p < 0.05).The radiomics nomogram indicated more effective prognostic performance compared with the clinicopathological model and tumor node metastasis staging system (p < 0.01), with a training C-index of 0.75 (95% confidence interval (CI), 0.71–0.80), an internal validation C-index of 0.73 (95% CI, 0.69–0.78) and an external validation 0.71 (95% CI,0.66–0.76). Moreover, the calibration curves revealed a good consistency for survival prediction of the radiomics model. The ultrasound-based radiomics signature was a promising biomarker for risk stratification for TNBC patients. Furthermore, the proposed radiomics modal integrating the optimal radiomics features and clinical data provided individual relapse risk accurately. The radiomics model integrating radiomic signature and independent clinicopathological variables could improve individual prognostic evaluation and facilitate therapeutic decision-making, which demonstrated the incremental value of the radiomics signature for prognostic prediction in TNBC. [ABSTRACT FROM AUTHOR]

This paper proposed a non-segmentation radiological method for classification of benign and malignant thyroid tumors using B mode ultrasound data. This method aimed to combine the advantages of morphological information provided by ultrasound and convolutional neural networks in automatic feature extraction and accurate classification. Compared with the traditional feature extraction method, this method directly extracted features from the data set without the need for segmentation and manual operations. 861 benign nodule images and 740 malignant nodule images were collected for training data. A deep convolution neural network VGG-16 was constructed to analyze test data including 100 malignant nodule images and 109 benign nodule images. A nine fold cross validation was performed for training and testing of the classifier. The results showed that the method had an accuracy of 86.12%, a sensitivity of 87%, and a specificity of 85.32%. This computer-aided method demonstrated comparable diagnostic performance with the result reported by an experienced radiologist based on American college of radiology thyroid imaging reporting and data system (ACR TI-RADS) (accuracy: 87.56%, sensitivity: 92%, and specificity: 83.49%). The automation advantage of this method suggested application potential in computer-aided diagnosis of thyroid cancer. [ABSTRACT FROM AUTHOR]

Objectives. The present study is aimed at evaluating the diagnostic value of combining shear wave elastography (SWE) parameters and the thyroid imaging reporting and data system (TIRADS) for differentiating between benign and malignant thyroid nodules. Methods. Patients who underwent conventional ultrasonography (US) and SWE before surgery were enrolled in the current study. Each nodule was given a TIRADS risk score. The effectiveness of the SWE parameters was assessed by odds ratios (ORs). The SWE scoring risk stratification was proposed beyond 95% probability, and the desired values were obtained according to the log-normal distribution. The area under the receiver-operating characteristic (AUC) was used to compare the diagnostic performance between TIRADS-alone and TIRADS + SWE. Results. A total of 262 patients with 298 thyroid nodules were enrolled in our study. The pathological analyses were conducted on 121 benign and 177 malignant nodules. The AUC values for TIRADS-alone and TIRADS + SWE were 0.896 (accuracy 83.2%) and 0.917 (accuracy 84.2%), respectively. However, the TIRADS + SWE scores showed a higher specificity (88.4%) and positive predictive value (91.2%) as compared with the TIRADS-alone of 73.6% and 83.2%, respectively. Conclusions. Combining SWE and TIRADS improves the specificity of TIRADS-alone in differentiating between benign and malignant thyroid nodules. [ABSTRACT FROM AUTHOR]

• Rational design and fabrication of Co catalysts embedded in N-doped carbon. • Good activity and recyclability for the optimized catalyst (Co@NC700-H 2 /Ar). • The correlation of pyrolysis conditions with the catalytic activity. • Exploration of the oxidation states of Co in different catalysts. In this work, a series of Co catalysts (namely Co@NC) was designed and developed from the thermal treatment of ZIF-67. Through extensive screening of various parameters, Co@NC700-H 2 /Ar exhibited the best catalytic performance in the acceptorless alcohol dehydrogenation to carboxylic acids. It was worth noting that Co@NC700-H 2 /Ar enabled the efficient synthesis of various aromatic and aliphatic carboxylic acids in moderate to high yields. Besides, it was recyclable for 9 consecutive cycles without activity decay. Moreover, the effects of pyrolysis conditions on the catalytic performance of the resulting materials were thoroughly examined, and the rationale for the superiority of Co@NC700-H 2 /Ar over the other prepared materials was also provided. Specifically, the pyrolysis atmosphere applying 95% of Ar gas and 5% of H 2 gas (H 2 /Ar) resulted in the generation of ideal porosity and carbon nanotubes (CNTs), while utilizing 700 °C as the optimized pyrolysis temperature was ascribed to the comprehensive evaluation of materials crystallinity and defective structures. Furthermore, additional insights were gained by systematically exploring the oxidation states of Co in different catalysts. It was proposed that the Co–N species played a crucial role in this catalysis, while the contribution of other Co species, including Co0 and Co–O, could not be neglected. Finally, a plausible reaction mechanism was proposed based on the above observations and related literature reports. [Display omitted] [ABSTRACT FROM AUTHOR]

The post-translational glycosylation of proteins by O-linked α-mannose is conserved from bacteria to humans. Due to advances in high-throughput mass spectrometry-based approaches, a variety of glycoproteins are identified to be O-mannosylated. Various proteins with O-mannosylation are involved in biological processes, providing essential necessity for proper growth and development. In this review, we summarize the process and regulation of O-mannosylation. The multi-step O-mannosylation procedures are quite dynamic and complex, especially when considering the structural and functional inspection of the involved enzymes. The widely studied O-mannosylated proteins in human include α-Dystroglycan (α-DG), cadherins, protocadherins, and plexin, and their aberrant O-mannosylation are associated with many diseases. In addition, O-mannosylation also contributes to diverse functions in lower eukaryotes and prokaryotes. Finally, we present the relationship between O-mannosylation and gut microbiota (GM), and elucidate that O-mannosylation in microbiome is of great importance in the dynamic balance of GM. Our study provides an overview of the processes of O-mannosylation in mammalian cells and other organisms, and also associated regulated enzymes and biological functions, which could contribute to the understanding of newly discovered O-mannosylated glycoproteins. [Display omitted] • O-mannosylation is conserved from mammalian cells to microorganisms. • The multi-step procedures are quite complex that involves many crucial enzymes. • Aberrant O-mannosylation is engaged in distinct pathological states. • O-mannosylation plays important roles in through gut microbiota. [ABSTRACT FROM AUTHOR]

Magnetic Fe 3 S 4 was facilely derived from MIL-100(Fe) as the precursor and thioacetamide (TAA) as the sulfur source under hydrothermal condition. The as-prepared Fe 3 S 4 was adopted as catalyst to promote the photo-Fenton process, in which sulfamethoxazole (SMX) was used as representative pollutant sample to test the oxidative degradation performance of Fe 3 S 4. The results showed that Fe 3 S 4 exhibited excellent photo-Fenton-like oxidation decomposition performances toward sulfamethoxazole (SMX) under both UV and visible light. A possible degradation mechanism over Fe 3 S 4 in the photo-Fenton reaction is put forward based on quenching experiments and electron spin resonance (ESR). About 41% total organic carbon (TOC) removal efficiency of sulfamethoxazole (SMX) over the as-prepared Fe 3 S 4 can be accomplished within 40 min. As well, different sulfonamide antibiotics (SAs) like sulfamethoxazole (SMX), sulfisoxazole (SIM) and sulfadiazine (SDZ) were selected to further investigate the oxidative degradation activity of Fe 3 S 4 in this photo-Fenton-like reaction system, in which the possible degradation pathways of SMX, SIM and SDZ were put forward based on UHPLC-MS analysis. This work provided a new strategy to prepare magnetic Fe 3 S 4 as catalyst for advanced oxidation process, which can be easily separated from the treated water samples to accomplish facile recovery and recyclability. [Display omitted] • The magnetic Fe 3 S 4 derived from MIL-100(Fe) was fabricated. • The sulfamethoxazole can be degraded over Fe 3 S 4 as photo-Fenton catalyst. • Fe 3 S 4 can be easily recovered for reuse under an external magnetic field. [ABSTRACT FROM AUTHOR]

Splicing of precursor messenger RNA (pre-mRNA) in eukaryotic cells is carried out by the spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs) and a number of accessory factors and enzymes. Each snRNP contains a ring-shaped subcomplex of seven proteins and a specific RNA molecule. The U6 snRNP contains a unique heptameric Lsm protein complex, which specifically recognizes the U6 small nuclear RNA at its 3′ end. Here we report the crystal structures of the heptameric Lsm complex, both by itself and in complex with a 3′ fragment of U6 snRNA, at 2.8 Å resolution. Each of the seven Lsm proteins interacts with two neighbouring Lsm components to form a doughnut-shaped assembly, with the order Lsm3-2-8-4-7-5-6. The four uridine nucleotides at the 3′ end of U6 snRNA are modularly recognized by Lsm3, Lsm2, Lsm8 and Lsm4, with the uracil base specificity conferred by a highly conserved asparagine residue. The uracil base at the extreme 3′ end is sandwiched by His 36 and Arg 69 from Lsm3, through π-π and cation-π interactions, respectively. The distinctive end-recognition of U6 snRNA by the Lsm complex contrasts with RNA binding by the Sm complex in the other snRNPs. The structural features and associated biochemical analyses deepen mechanistic understanding of the U6 snRNP function in pre-mRNA splicing. [ABSTRACT FROM AUTHOR]

• A lung ultrasonography algorithm using radiofrequency signal was proposed. • Analysis based on 2D spectrum is performed to improve lung diagnostic accuracy. • Frequency spectrum standard deviation slopes (FSSDS) were quantitatively analyzed. • FSSDS method is more sensitive and accurate than 4-point scaling method. Lung diseases are commonly diagnosed based on clinical pathological indications criteria and radiological imaging tools (e.g. , X-rays and CT). During a pandemic like COVID-19, the use of ultrasound imaging devices has broadened for emergency examinations by taking their unique advantages such as portability, real-time detection, easy operation and no radiation. This provides a rapid, safe, and cost-effective imaging modality for screening lung diseases. However, the current pulmonary ultrasound diagnosis mainly relies on the subjective assessments of sonographers, which has high requirements for the operator's professional ability and clinical experience. In this study, we proposed an objective and quantifiable algorithm for the diagnosis of lung diseases that utilizes two-dimensional (2D) spectral features of ultrasound radiofrequency (RF) signals. The ultrasound data samples consisted of a set of RF signal frames, which were collected by professional sonographers. In each case, a region of interest of uniform size was delineated along the pleural line. The standard deviation curve of the 2D spatial spectrum was calculated and smoothed. A linear fit was applied to the high-frequency segment of the processed data curve, and the slope of the fitted line was defined as the frequency spectrum standard deviation slope (FSSDS). Based on the current data, the method exhibited a superior diagnostic sensitivity of 98% and an accuracy of 91% for the identification of lung diseases. The area under the curve obtained by the current method exceeded the results obtained that interpreted by professional sonographers, which indicated that the current method could provide strong support for the clinical ultrasound diagnosis of lung diseases. [ABSTRACT FROM AUTHOR]

Sodium–glucose cotransporter 2 inhibitors, efficacious antidiabetic agents that have cardiovascular and renal benefits, can promote pancreatic β-cell regeneration in type 2 diabetic mice. However, the underlying mechanism remains unclear. In this study, we aimed to use multiomics to identify the mediators involved in β-cell regeneration induced by dapagliflozin. We showed that dapagliflozin lowered blood glucose level, upregulated plasma insulin level, and increased islet area in db/db mice. Dapagliflozin reshaped gut microbiota and modulated microbiotic and plasmatic metabolites related to tryptophan metabolism, especially l-tryptophan, in the diabetic mice. Notably, l-tryptophan upregulated the mRNA level of glucagon-like peptide 1 (GLP-1) production–related gene (Gcg and Pcsk1) expression and promoted GLP-1 secretion in cultured mouse intestinal L cells, and it increased the supernatant insulin level in primary human islets, which was eliminated by GPR142 antagonist. Transplant of fecal microbiota from dapagliflozin-treated mice, supplementation of l-tryptophan, or treatment with dapagliflozin upregulated l-tryptophan, GLP-1, and insulin or C-peptide levels and promoted β-cell regeneration in db/db mice. Addition of exendin 9-39, a GLP-1 receptor (GLP-1R) antagonist, or pancreatic Glp1r knockout diminished these beneficial effects. In summary, treatment with dapagliflozin in type 2 diabetic mice promotes β-cell regeneration by upregulating GLP-1 production, which is mediated via gut microbiota and tryptophan metabolism. Article Highlights: Sodium–glucose cotransporter 2 inhibitors, novel and efficacious antidiabetic agents, can preserve β-cell mass in type 2 diabetic animals, but the mechanism remains unclear. We find that dapagliflozin reshapes gut microbiota, improves microbiotic and plasmatic metabolites related to tryptophan metabolism, and increases glucagon-like peptide 1 (GLP-1) production mediated via tryptophan metabolism. GLP-1−GLP-1 receptor signaling participates in the dapagliflozin-induced β-cell regeneration. Our study reveals that the gut microbiota–tryptophan metabolism–GLP-1 axis is a novel mechanism of β-cell regeneration induced by dapagliflozin and provides experimental evidence for its β-cell protection in treating type 2 diabetes. [ABSTRACT FROM AUTHOR]

This study was aimed at evaluating the performance of perfusion patterns and the quantitative parameters of contrast-enhanced ultrasound (CEUS) in the detection of soft tissue tumors (STTs) and establishing a US workflow for STTs to improve patient management. Conventional ultrasound (US) and CEUS data were retrospectively collected from 156 soft tissue masses. Six perfusion patterns (P1-P6) were applied for CEUS qualitative analysis. Multivariate logistic regression was used to evaluate the performance of conventional US and qualitative and quantitative CEUS in distinguishing benign and malignant STTs. The malignancy rates of P1-P6 in STTs were 0%, 50.0%, 9.1%, 33.3%, 73.4% and 61.0%, respectively. For "non-P1" STTs, the predictive model combining quantitative CEUS parameters with conventional US features, including margin (odds ratio [OR] = 4.490, p = 0.000), vascular density (OR = 2.307, p = 0.013), 50% wash-out intensity (OR = 1.904, p = 0.032) and 50% wash-out time (OR = 1.031, p = 0.019), performed favorably in predicting malignancy, with an accuracy of 81.0% and an area under the receiver operating characteristic curve of 0.868. Furthermore, a US workflow for the detection of STTs based on conventional US and CEUS was established. CEUS with qualitative and quantitative analyses could be an effective tool for STT diagnosis. The US workflow in this study may improve the management of STT patients. [ABSTRACT FROM AUTHOR]

Early prediction of the onset, progression and prognosis of acute ischemic stroke (AIS) is helpful for treatment decision-making and proactive management. Although several biomarkers have been found to predict the progression and prognosis of AIS, these biomarkers have not been widely used in routine clinical practice. Xanthine oxidase (XO) is a form of xanthine oxidoreductase (XOR), which is widespread in various organs of the human body and plays an important role in redox reactions and ischemia‒reperfusion injury. Our previous studies have shown that serum XO levels on admission have certain clinical predictive value for AIS. The purpose of this study was to utilize serum XO levels and clinical data to establish machine learning models for predicting the onset, progression, and prognosis of AIS. We enrolled 328 consecutive patients with AIS and 107 healthy controls from October 2020 to September 2021. Serum XO levels and stroke-related clinical data were collected. We established 5 machine learning models—the logistic regression (LR), support vector machine (SVM), decision tree, random forest, and K-nearest neighbor (KNN) models—to predict the onset, progression, and prognosis of AIS. The area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, negative predictive value, and positive predictive value were used to evaluate the predictive performance of each model. Among the 5 machine learning models predicting AIS onset, the AUROC values of 4 prediction models were over 0.7, while that of the KNN model was lower (AUROC = 0.6708, 95% CI 0.576–0.765). The LR model showed the best AUROC value (AUROC = 0.9586, 95% CI 0.927–0.991). Although the 5 machine learning models showed relatively poor predictive value for the progression of AIS (all AUROCs <0.7), the LR model still showed the highest AUROC value (AUROC = 0.6543, 95% CI 0.453–0.856). We compared the value of 5 machine learning models in predicting the prognosis of AIS, and the LR model showed the best predictive value (AUROC = 0.8124, 95% CI 0.715–0.910). The tested machine learning models based on serum levels of XO could predict the onset and prognosis of AIS. Among the 5 machine learning models, we found that the LR model showed the best predictive performance. Machine learning algorithms improve accuracy in the early diagnosis of AIS and can be used to make treatment decisions. [ABSTRACT FROM AUTHOR]

Male infertility is one of the most common complications of diabetes mellitus (DM). Dapagliflozin is widely used to manage the type II DM. This study aimed to assess the dapagliflozin's effects on the spermatogenesis by administering either dapagliflozin (Dapa) or vehicle (db) to male db/db mice, and using littermate male db/m mice as the control (Con). We further performed the integrative analyses of the cecal shotgun metagenomics, cecal/plasmatic/testicular metabolomics, and testicular proteomics. We found that dapagliflozin treatment significantly alleviated the diabetes-induced spermatogenic dysfunction by improving sperm quality, including the sperm concentration and sperm motility. The overall microbial composition was reshaped in Dapa mice and 13 species (such as Lachnospiraceae bacterium 3–1) were regarded as potential beneficial bacteria. Metabolites exhibited modified profiles, in which adenosine, cAMP, and 2′-deoxyinosine being notably altered in the cecum, plasma, and testis, respectively. Testicular protein expression patterns were similar between the Dapa and Con mice. In vivo results indicated that when compared with db group, dapagliflozin treatment alleviated apoptosis and oxidative stress in testis tissues by down-regulating 2′-deoxyinosine. This was further validated by in vitro experiments using GC-2 cells. Our findings support the potential use of dapagliflozin to prevent the diabetes-induced impaired sperm quality and to treat diabetic male infertility. [ABSTRACT FROM AUTHOR]

Background: Intellectual disability (ID) is characterized by an IQ < 70, which implies below-average intellectual function and a lack of skills necessary for daily living. ID may occur due to multiple causes, such as metabolic, infectious, and chromosomal causes. ID affects approximately 1–3% of the population; however, the cause can be identified in only 25% of clinical patients. Methods: To find the cause of genetic ID in a family, we performed whole-exome sequencing and Sanger sequencing to confirm the presence of a SETBP1 variant and real-time quantitative polymerase chain reaction to detect SETBP1 expression in the proband and normal controls. Results: A novel variant, c.942_943insGT (p. Asp316TrpfsTer28), was found in SETBP1. Furthermore, we observed that SETBP1 expression in patients was only 20% that of normal controls (P < 0.05). Conclusion: A heterozygous variant in SETBP1 associated with ID was found. This report provides further evidence for its genetic basis and support for clinical genetic diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the predictive performance of the deep learning radiomics (DLR) model integrating pretreatment ultrasound imaging features and clinical characteristics for evaluating therapeutic response after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Methods: A total of 603 patients who underwent NAC were retrospectively included between January 2018 and June 2021 from three different institutions. Four different deep convolutional neural networks (DCNNs) were trained by pretreatment ultrasound images using annotated training dataset (n = 420) and validated in a testing cohort (n = 183). Comparing the predictive performance of these models, the best one was selected for image-only model structure. Furthermore, the integrated DLR model was constructed based on the image-only model combined with independent clinical-pathologic variables. Areas under the curve (AUCs) of these models and two radiologists were compared by using the DeLong method. Results: As the optimal basic model, Resnet50 achieved an AUC and accuracy of 0.879 and 82.5% in the validation set. The integrated DLR model, yielding the highest classification performance in predicting response to NAC (AUC 0.962 and 0.939 in the training and validation cohort), outperformed the image-only model and the clinical model and also performed better than two radiologists' prediction (all p < 0.05). In addition, predictive efficacy of the radiologists was improved under the assistance of the DLR model significantly. Conclusion: The pretreatment US-based DLR model could hold promise as a clinical guidance for predicting NAC response of patients with breast cancer, thereby providing benefit of timely treatment strategy adjustment to potential poor NAC responders. Key Points: • Multicenter retrospective study showed that deep learning radiomics (DLR) model based on pretreatment ultrasound image and clinical parameter achieved satisfactory prediction of tumor response to neoadjuvant chemotherapy (NAC) in breast cancer. • The integrated DLR model could become an effective tool to guide clinicians in identifying potential poor pathological responders before chemotherapy. • The predictive efficacy of the radiologists was improved under the assistance of the DLR model. [ABSTRACT FROM AUTHOR]

Aims: To put forward a scientific hypothesis about the progression of insulin-injection-induced lipohypertrophy (LH) according to the high-frequency ultrasonic imaging of insulin injection sites and the blood glucose control of patients. Methods: A total of 344 patients were screened for LH by means of high-frequency ultrasound scanning. The results of their ultrasound examination were described in detail and categorized into several subtypes. Seventeen patients with different subtypes of LH were followed up to predict the progression of LH. To further verify our hypothesis, the effects of different types of LH on glycemic control of patients were observed by comparing glycated hemoglobin A1c (HbA1C) and other glycemic-related indicators. Results: LH was found in 255 (74.1%) patients. According to the high-frequency ultrasonic imaging characteristics, LH can be categorized into three subtypes in general. Among all the LHs, the most common type observed was nodular hyperechoic LH (n = 167, 65.5%), followed by diffuse hyperechoic LH (n = 70, 27.5%), then hypoechoic LH (n = 18, 7.0%). At the follow-up after six months, all 10 patients with nodular hyperechoic LH had LH faded away. Of the five patients with diffuse hyperechoic LH, two had inapparent LH, and three had diffuse hyperechoic parts which had shrunk under ultrasound. No obvious changes were observed in the two cases of hypoechoic LH. Compared with the LH-free group, the mean HbA1C of the nodular hyperechoic LH group increased by 0.8% (9 mmol/mol) (95% CI:−1.394~−0.168, p = 0.005), that of the diffuse hyperechoic LH group increased by 2.0% (21 mmol/mol) (95% CI: −2.696~−1.20, p < 0.001), and that of the hypoechoic LH group increased by 1.5% (16 mmol/mol) (95% CI: −2.689~−0.275, p = 0.007). Conclusions: It was hypothesized that the earlier stage of LH is nodular hyperechoic LH. If nodular LH is not found in time and the patient continues to inject insulin at the LH site and/or reuse needles, LH will develop into a diffuse type or, even worse, a hypoechoic one. Different subtypes of LH may represent differences in severity when blood glucose control is considered as an important resolution indicator. Further studies are needed to confirm our hypothesis on the progression and reversion of insulin-induced lipohypertrophy. [ABSTRACT FROM AUTHOR]

(1) Background: Non-obstructive azoospermia (NOA) is a complex multifactorial disease and the causes of most NOA cases remain unknown. (2) Methods: Here, we performed comprehensive clinical analyses and gut microbial profiling using shotgun metagenomic sequencing in patients with NOA and control individuals. (3) Results: The gut microbial alpha and beta diversity significantly differed between patients with NOA and controls. Several microbial strains, including Bacteroides vulgatus and Streptococcus thermophilus, were significantly more abundant in the NOA group, whereas Bacteroides thetaiotaomicron and Parabacteroides sp. CT06 were enriched in the control group. Moreover, functional pathway analysis suggested that the altered microbiota in NOA suppressed the carbohydrate metabolism pathway, while amino acid metabolism and methane metabolism pathways were enhanced. We observed that the differential microbial species, such as Acinetobacter johnsonii, had a strong correlation with clinical parameters, including age, body mass index, testosterone, and follicle-stimulating hormone. Communication and interplay among microbial genera were significantly increased in NOA than in the control group. (4) Conclusions: Altered microbial composition and functional pathways in the NOA group were revealed, which highlight the utility of gut microbiota in understanding microbiota-related pathogenesis of NOA and might be helpful to the clinical management of NOA. [ABSTRACT FROM AUTHOR]

INTRODUCTION Many smokers have not accessed professional smoking cessation assistance due to limited smoking cessation services. We developed a novel mHealth-based integrated modality for smoking cessation (WeChat + Quitline modality, WQ modality) and applied it to a large public welfare project (China Western-QUIT Program) in western China. This study evaluated the usage, acceptability, and preliminary effectiveness of the WQ modality in the population of western China. METHODS A prospective cohort study was conducted between April and August 2021. Smokers or their relatives were recruited through online advertisements and medical staff referrals. After using the services of the WQ modality for one month, the self-reported awareness, use, and satisfaction with each service among the participants were collected by a telephone interview. We also evaluated the self-reported 7-day point prevalence of abstinence (PPA) and quit attempt rate among baseline current smokers. The usage data of each service were downloaded from quitline and WeChat platforms. RESULTS Of the 17326 people from western China using the WQ modality, the largest number of users was WeChat official account (11173), followed by WeChat mini program (3734), WeChat group (669), and quitline (541 inbound calls, 605 outbound calls). At one month follow-up, over 70% of participants who completed the baseline survey (n=2221) were aware of WeChat-based services, and over 50% used them. However, the awareness rate (11.1%) and utilization rate (0.5%) of quitline were relatively low. The median satisfaction scores across all services were 9 out of 10 points (IQR: 8-9). Among the baseline current smokers (n=1257), self-reported 7-day PPA was 41.8% (526/1257), and another 225 smokers (17.9%) reported making a quit attempt. CONCLUSIONS The WQ modality could be well used and accepted, and it has great potential to motivate and aid short-term smoking cessation in smokers from western China. [ABSTRACT FROM AUTHOR]

[Display omitted] • The first MOF catalyst was developed for the alcohol dehydrogenation to carboxylates. • The Zn-based MOF catalyst was prepared in a facile and environmental-friendly manner. • The catalyst could be reused at least 5 consecutive times without activity decay. • Aldehyde as a key intermediate and [Zn-N] as the active sites were proposed. Zeolitic imidazolate framework-8 (ZIF-8) is a representative Zn-based metal–organic framework (MOF) featuring high porosity, good stability, and large surface area. Owing to these fascinating properties, ZIF-8 exhibits promising potential in catalysis. With our continuous interest in catalyst development of alcohol-involving green transformations, we intended to exploit the capability of ZIF-8 in catalyzing the acceptorless dehydrogenation of alcohols to carboxylates. The preparation of ZIF-8 at room temperature possesses advantages such as environmental friendliness and easy operation. Subsequently, various techniques were adopted to characterize the structures, morphology, and chemical states of both fresh and reused catalysts. Notably, the catalyst displayed good reusability since it could be reused at least 5 times without considerable loss of catalytic activity. It was also perceived that KOH was an indispensable component of this catalytic process. More specifically, KOH not only worked as one of the starting materials but also provided the basic environment to promote this catalysis. Furthermore, the aldehyde was confirmed as a key intermediate for this catalytic process. Based on additional experiments and literature reports, we proposed [Zn–N] as the active sites and presented a plausible catalytic cycle. [ABSTRACT FROM AUTHOR]

Background: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China.Methods: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation.Conclusions: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653. [ABSTRACT FROM AUTHOR]

Background: Chordomas are rare, slow-growing and locally aggressive bone sarcomas. At present, chordomas are difficult to manage due to their high recurrence rate, metastasis tendency and poor prognosis. The underlying mechanisms of chordoma tumorigenesis and progression urgently need to be explored to find the effective therapeutic targets. Our previous data demonstrates that EGFR plays important roles in chordoma development and CKLF-like MARVEL transmembrane domain containing (CMTM)3 suppresses gastric cancer metastasis by inhibiting the EGFR/STAT3/EMT signaling pathway. However, the roles and mechanism of CMTM3 in chordomas remain unknown. Methods: Primary chordoma tissues and the paired adjacent non-tumor tissues were collected to examine the expression of CMTM3 by western blot. The expression of CMTM3 in chordoma cell lines was tested by Real-time PCR and western blot. CCK-8 and colony forming unit assay were performed to delineate the roles of CMTM3 in cell proliferation. Wound healing and Transwell assays were performed to assess cell migration and invasion abilities. A xenograft model in NSG mice was used to elucidate the function of CMTM3 in vivo. Signaling pathways were analyzed by western blot and IHC. RNA-seq was performed to further explore the mechanism regulated by CMTM3 in chordoma cells. Results: CMTM3 expression was downregulated in chordoma tissues compared with paired normal tissues. CMTM3 suppressed proliferation, migration and invasion of chordoma cells in vitro and inhibited tumor growth in vivo. CMTM3 accelerated EGFR degradation, suppressed EGFR/STAT3/EMT signaling pathway, upregulated TP53 expression and enriched the TP53 signaling pathway in chordoma cells. Conclusions: CMTM3 inhibited tumorigenesis and development of chordomas through activating the TP53 signaling pathway and suppressing the EGFR/STAT3 signaling pathway, which suppressed EMT progression. CMTM3 might be a potential therapeutic target for chordomas. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical application of high-frequency ultrasound in the screening of lipohypertrophy (LH). Methods This was a cross-section study. A total of 548 diabetic patients who received insulin injection more than six months were recruited from November 2016 to September 2020 in the First Affiliated Hospital of Nanjing Medical University. Clinical data and insulin injection duration of patients were collected, the patients were examined through visual and palpation and ultrasound. The t-test, nonparametric test or Chi square test was used to compare the count data between groups. Results Of the 548 patients, 418 patients were found to have LH detected by clinical examination, 478 patients by ultrasound, 390 patients both by clinical examination and ultrasound. The detectable rate of LH by high-frequency ultrasound was higher than that by the clinical examination [76.3% (418/548) vs. 87.2% (478/548), χ² =59.998, P<0.01]. Compared with those detected by ultrasound only, the mean depth, median length, median width and median area of LH detected both by clinical examination and ultrasound examination were higher, with a statistically significant difference in the width diameter (P<0.05). The imaging features of LH included three types ( hyperechoic, isoechoic, hypoechoic) and five subtypes. Among them, the most common type was hyperechoic type, which had no blood flow, no capsule, and uniform mass with unclear boundary, accounting for 65.9% (315/478). Compared with LH detected by high-ultrasound only, the mean deep diameter, length diameter, width diameter and area of LH detected both by clinical examination and ultrasound examination were all increased, and the difference of width diameter was statistically significant [8.67 (7.66, 13.21) mm vs. 13.47 (8.70, 18.22) mm, Z=-2.135, P<0.05]. Conclusion In addition to the traditional clinical examination (visualization and palpation), high-frequency ultrasound can be used as an important supplement to the examination of insulin injection site in diabatic patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the epidemiology, clinical features, treatment and outcome of Noninvasive ventilation (NIV)‐treated acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients in secondary hospitals of Shanghai. Method: Relying on Shanghai alliances for respiratory diseases, a retrospective observational study was performed in 34 secondary hospitals of Shanghai. The AECOPD patients treated with NIV and admitted to the respiratory department or respiratory intensive care unit were recruited between December 1, 2016, and November 30, 2017. Results: There were 555 patients finally recruited in this study. The age was 75.8 ± 9.6 years old and 380 patients (68.5%) were male. 70.5% of all patients had respiratory acidosis (pH <7.35). 55.3% of all patients received nebulised bronchodilator and 77.7% were treated with systemic or inhaled corticosteroids during hospitalisation. 525 patients (94.6%) recovered successfully and the mortality was 3.2%. The hospitalisation was 15.3 ± 6.7 days and hospital expenses were 22 911 ± 13 595 RMB. Inadequate and nonstandard drug treatments were the most important problems during management. Conclusion: The NIV can be successfully used for AECOP patients in local hospitals of Shanghai, but accompanied by high costs and long hospital stays. However, the treatments for exacerbation and stable COPD patients are still insufficient. [ABSTRACT FROM AUTHOR]

Background: Copy number variation (CNV) suggests genetic changes in malignant tumors. Abnormal expressions of long non-coding RNAs (lncRNAs) resulted from genomic and epigenetic abnormalities play a driving role in tumorigenesis of cervical cancer. However, the role of lncRNAs-related CNV in cervical cancer remained largely unclear.Methods: The data of messenger RNAs (mRNAs), DNA methylation, and DNA copy number were collected from 292 cervical cancer specimens. The prognosis-related subtypes of cervical cancer were determined by multi-omics integration analysis, and protein-coding genes (PCGs) and lncRNAs with subtype-specific expressions were identified. The CNV pattern of the subtype-specific lncRNAs was analyzed to identify the subtype-specific lncRNAs. A prognostic risk model based on lncRNAs was established by least absolute shrinkage and selection operator (LASSO).Results: Multi-omics integration analysis identified three molecular subtypes incorporating 617 differentially expressed lncRNAs and 1395 differentially expressed PCGs. The 617 lncRNAs were found to intersect with disease-related lncRNAs. Functional enrichment showed that 617 lncRNAs were mainly involved in tumor metabolism, immunity and other pathways, such as p53 and cAMP signaling pathways, which are closely related to the development of cervical cancer. Finally, according to CNV pattern consistent with differential expression analysis, we established a lncRNAs-based signature consisted of 8 lncRNAs, namely, RUSC1-AS1, LINC01990, LINC01411, LINC02099, H19, LINC00452, ADPGK-AS1, C1QTNF1-AS1. The interaction of the 8 lncRNAs showed a significantly poor prognosis of cervical cancer patients, which has also been verified in an independent dataset.Conclusion: Our study expanded the network of CNVs and improved the understanding on the regulatory network of lncRNAs in cervical cancer, providing novel biomarkers for the prognosis management of cervical cancer patients. [ABSTRACT FROM AUTHOR]

What are the proteomic and phosphoproteomic differences between the endometrium of women with recurrent pregnancy loss (RPL) and the endometrium of healthy control women during the proliferative and secretory phases of the menstrual cycle? In total, 54 endometrial samples were collected during the proliferative and secretory phases from women with RPL (n = 28) and healthy controls (n = 26). Comprehensive proteomic and phosphoproteomic analyses were conducted using label-free liquid chromatography-tandem mass spectrometry (n = 44), and verified through Western blotting (n = 10). Three comparison groups were established: total RPL endometrium versus total control endometrium; RPL proliferative endometrium versus control proliferative endometrium; and RPL secretory endometrium versus control secretory endometrium. Differentially expressed proteins and differentially phosphorylated proteins were identified in the three comparison groups. Combining pathway enrichment, network analysis and soft clustering analysis, the insulin/cyclic nucleotide signalling pathway and AMPK/mTOR signalling pathway were identified as the major contributors to the aberration of RPL endometrium. Western blotting verified altered expression of four proteins: cAMP-dependent protein kinase type I-β regulatory subunit, adenylate cyclase type 3, 5'-AMP-activated protein kinase catalytic subunit α-2 and phosphatidate phosphatase LPIN2. This exploratory study provides insights into the differentiated protein expression and phosphorylation profiles of the endometrium of women with RPL in both the proliferative and sectretory phases of the menstrual cycle. The results highlight potential proteins associated with the pathogenesis of RPL that may serve as potential indicators for RPL. The findings contribute to the identification of potential targets for RPL treatment as well as its pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between KLOTHO expression and diminished ovarian reserve (DOR).Design: A case-control study.Setting: Reproductive medicine center.Patient(s): A total of 157 patients with DOR and 159 control women were recruited from the Centre of Reproductive Medicine, Peking University Third Hospital.Intervention(s): None.Main Outcome Measure(s): The granulosa cells were isolated from follicular fluid after oocyte retrieval, and the KLOTHO level of granulosa cell was measured using a modified quantitative polymerase chain reaction technique. The serum KLOTHO level was measured by solid-phase sandwich enzyme-linked immunosorbent assay.Result(s): In both granulosa cells and serum derived from women with DOR, KLOTHO expressions were significantly lower compared with normal ovarian reserve controls. Moreover, KLOTHO expression diminished with advancing age.Conclusion(s): Diminished KLOTHO expression was associated with DOR. Further longitudinal studies in a similar population accompanying disease progression and mechanism exploration are needed to substantiate the rules of KLOTHO in reproductive aging. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are central effector cells in allergic reactions that are often mediated by immunoglobulin E (IgE). Allergies commonly start at an early age, and both MCs and IgE are detectable in fetuses. However, the origin of fetal IgE and whether fetal MCs can degranulate in response to IgE-dependent activation are presently unknown. Here, we show that human and mouse fetal MCs phenotypically mature through pregnancy and can be sensitized by maternal IgE. IgE crossed the placenta, dependent on the fetal neonatal Fc receptor (FcRN), and sensitized fetal MCs for allergen-specific degranulation. Both passive and active prenatal sensitization conferred allergen sensitivity, resulting in postnatal skin and airway inflammation after the first allergen encounter. We report a role for MCs within the developing fetus and demonstrate that fetal MCs may contribute to antigen-specific vertical transmission of allergic disease. [ABSTRACT FROM AUTHOR]

MIL-68, a typical In-based MOF, has been studied in many fields due to its excellent performance. Facile preparation of MIL-68, suitable for scalable preparation and industrial applications, is of great significance. In this work, a method for the room-temperature preparation of rod-like MIL-68 at the nano- and micro-scales was developed for the first time, in which water or salts such as NaF, sodium formate, sodium acetate and sodium propionate were used as modulating reagents. It appears that these modulating reagents can promote the deprotonation of terephthalic acid and the hydrolysis of indium salt to accelerate crystal nucleation. The size of MIL-68 can be controlled by changing the modulating reagents. Hollow porous In 2 S 3 particles composed of assembled ultrathin nanosheets were obtained via sulfidation treatment using MIL-68 as a self-sacrifice template, and the obtained In 2 S 3 exhibited excellent photocatalytic activity toward Cr(VI) reduction and methyl orange degradation under LED visible light irradiation. Furthermore, the photocatalytic mechanism and reusability were studied. Image 1 • A facile preparation method of MIL-68 was developed using water or salts as modulating reagents. • The sizes of MIL-68 can be controlled by changing the modulating reagents. • Hollow In 2 S 3 with assembled ultrathin nanosheets derived from MIL-68 was obtained. • The In 2 S 3 exhibited excellent photocatalytic performance under LED visible light. • The photocatalytic mechanism was proposed. [ABSTRACT FROM AUTHOR]

Background and purpose: A higher Totaled Health Risks in Vascular Events (THRIVE) score has been shown to predict poor functional outcome in patients with acute ischemic stroke (AIS) and anterior circulation large vessel occlusions undergoing thrombectomy treatment. We attempted to evaluate the value of the THRIVE score in predicting the outcome of thrombectomy treatment in AIS patients with basilar artery occlusion (BAO). Methods: A total of 68 AIS patients with BAO who underwent thrombectomy treatment from May 2014 to August 2018 were included in the present study. Multivariable logistic regression was performed to determine the predictive value of the THRIVE score for poor functional outcome (defined as modified Rankin Scale score ≥ 3), all‐cause mortality, and hemorrhage transformation (HT) at 3 months. Results: A total of 42 (61.8%) participants experienced poor functional outcomes, 25 (36.8%) patients died from all causes, and 21 (30.9%) patients had HT during the 3‐month follow‐up. Multivariable logistic regression showed that a higher THRIVE score was significantly associated with poor functional outcome (odds ratio [OR] 5.86, 95% confidence interval [CI], 2.28–14.91, p < .001) as well as all‐cause mortality (OR 2.40, 95% CI, 1.32–4.34, p = .004) but not HT (p = .607). The C‐statistic of the THRIVE score was significantly larger than that of the NIHSS score for predicting poor functional outcome (AUC = 0.913; cutoff > 5; sensitivity, 88.5%; specificity, 83.3%, p = .007) and all‐cause mortality (AUC = 0.768; cutoff > 5; sensitivity, 92.0%; specificity, 65.1%, p = .018). Conclusions: A high THRIVE score was independently associated with an increased risk of poor functional outcome and all‐cause mortality in AIS patients with BAO who underwent thrombectomy treatment. Moreover, the THRIVE score appeared to be a better predictor of clinical outcome than the NIHSS score. [ABSTRACT FROM AUTHOR]

Acute exacerbation (AE) is the main cause of increased disability and mortality for patients with Chronic Obstructive Pulmonary Disease (COPD). Short-term re-exacerbation after discharge is common for in-hospital patients with AECOPD. Thus, we aimed to design a scoring system to effectively predict the 30-day re-exacerbation using simple and easily accessible variables. We retrospectively enrolled 686 cases hospitalized for AECOPD in two Chinese hospitals from 2005 to 2017. A variety of parameters were collected like demographics, clinical manifestations and treatments in stable and AE period. The optimal subset of covariates in the multivariate logistic analysis was identified by the smallest Akaike Information Criterion (AIC) and was further used to develop a practical and reliable nomogram to predict the 30-day re-exacerbation. The efficacy of the nomogram was internally validated by concordance index (C-index) and a calibration plot. The incidence of 30-day re-exacerbation was 15.8%. Based on the smallest AIC, eight easily-accessible parameters were included in the nomogram, including sex, COPD assessment test (CAT) scores, AE with respiratory failure in the previous year, new purulent sputum, new cardiovascular events, combined antibiotic therapy, theophylline therapy for AE and ICU admission. Our nomogram revealed good discriminative ability with the C-index of 0.702. The calibration curve showed good agreement between nomogram-predicted probability and actual observation. Incorporating eight common variables, a nomogram for 30-day re-exacerbation after discharge with high predictive performance was constructed for patients with AECOPD, which was helpful in predicting individualized risk of re-exacerbation and offering individualized post-discharge support. [ABSTRACT FROM AUTHOR]

Summary Mechanistic understanding of pre-mRNA splicing requires detailed structural information on various states of the spliceosome. Here we report the cryo electron microscopy (cryo-EM) structure of the human spliceosome just before exon ligation (the C ∗ complex) at an average resolution of 3.76 Å. The splicing factor Prp17 stabilizes the active site conformation. The step II factor Slu7 adopts an extended conformation, binds Prp8 and Cwc22, and is poised for selection of the 3′-splice site. Remarkably, the intron lariat traverses through a positively charged central channel of RBM22; this unusual organization suggests mechanisms of intron recruitment, confinement, and release. The protein PRKRIP1 forms a 100-Å α helix linking the distant U2 snRNP to the catalytic center. A 35-residue fragment of the ATPase/helicase Prp22 latches onto Prp8, and the quaternary exon junction complex (EJC) recognizes upstream 5′-exon sequences and associates with Cwc22 and the GTPase Snu114. These structural features reveal important mechanistic insights into exon ligation. [ABSTRACT FROM AUTHOR]

Brain macrophage populations include parenchymal microglia, border-associated macrophages, and recruited monocyte-derived cells; together, they control brain development and homeostasis but are also implicated in aging pathogenesis and neurodegeneration. The phenotypes, localization, and functions of each population in different contexts have yet to be resolved. We generated a murine brain myeloid scRNA-seq integration to systematically delineate brain macrophage populations. We show that the previously identified disease-associated microglia (DAM) population detected in murine Alzheimer's disease models actually comprises two ontogenetically and functionally distinct cell lineages: embryonically derived triggering receptor expressed on myeloid cells 2 (TREM2)-dependent DAM expressing a neuroprotective signature and monocyte-derived TREM2-expressing disease inflammatory macrophages (DIMs) accumulating in the brain during aging. These two distinct populations appear to also be conserved in the human brain. Herein, we generate an ontogeny-resolved model of brain myeloid cell heterogeneity in development, homeostasis, and disease and identify cellular targets for the treatment of neurodegeneration. [Display omitted] • M-Verse as a global cross-comparison of developing and adult murine brain macrophages • DAM correspond to a fetal-like reprogramming similar to Youth-Associated Microglia • DIMs appear during aging and increase in neurodegenerative diseases • DAM are embryonic derived, whereas DIMs are TREM2-independent monocyte derived Through 6 scRNA-seq brain dataset integration, the authors generated a myeloid map called M-Verse to delineate macrophage population heterogeneity. M-Verse revealed two distinct macrophage populations expressing published disease-associated microglia (DAM) signature: embryonically derived TREM2-dependent DAM and monocyte-derived TREM2-independent disease inflammatory macrophages (DIMs). [ABSTRACT FROM AUTHOR]

Background: An inverse association between socioeconomic status and pulmonary function has emerged in many studies. However, the mediating factors in this relationship are poorly understood, and might be expected to differ between countries. We sought to investigate the relationship between socioeconomic status and lung function in China, a rapidly industrializing nation with unique environmental challenges, and to identify potentially-modifiable environmental mediators.Methods: We used data from the Shanghai Putuo Study, a cross-sectional study performed in Shanghai, China. Participants completed a questionnaire and spirometry. The primary exposure was socioeconomic status, determined by education level. The primary outcomes were FEV1 and FVC percent predicted. Multiple linear regressions were used to test this association, and the percent explained by behavioral, environmental, occupational, and dietary variables was determined by adding these variables to a base model.Results: The study population consisted of a total of 22,878 study subjects that were 53.3 % female and had a mean age of 48. In the final multivariate analysis, the effect estimates for FEV1 and FVC percent predicted for low socioeconomic status (compared to high) were statistically significant at a p-value of <0.01. Smoking, biomass exposure, mode of transportation to work, a diet low in fruits or vegetables, and occupational category partially attenuated the relationship between SES and lung function. In a fully-adjusted age-stratified analysis, the socioeconomic disparity in lung function widened with increasing age.Conclusions: We found cross-sectional evidence of socioeconomic disparities in pulmonary function in Shanghai. These differences increased with age and were partially explained by potentially modifiable exposures. [ABSTRACT FROM AUTHOR]

Aims: The mechanisms underlying numerous biological roles of hydrogen sulfide (H2S) remain largely unknown. We have previously reported an inhibitory role of H2S in the L-type calcium channels in cardiomyocytes. This prompts us to examine the mechanisms underlying the potential regulation of H2S on the ion channels. Results: H2S showed a novel inhibitory effect on Ito potassium channels, and this effect was blocked by mutation at the Cys320 and/or Cys529 residues of the Kv4.2 subunit. H2S broke the disulfide bridge between a pair of oxidized cysteine residues; however, it did not modify single cysteine residues. H2S extended action potential duration in epicardial myocytes and regularized fatal arrhythmia in a rat model of myocardial infarction. H2S treatment significantly increased survival by ∼1.4-fold in the critical 2-h time window after myocardial infarction with a protection against ventricular premature beats and fatal arrhythmia. However, H2S did not change the function of other ion channels, including IK1 and INa. Innovation and Conclusion: H2S targets the Cys320/Cys529 motif in Kv4.2 to regulate the Ito potassium channels. H2S also shows a potent regularizing effect against fatal arrhythmia in a rat model of myocardial infarction. The study provides the first piece of evidence for the role of H2S in regulating Ito potassium channels and also the specific motif in an ion channel labile for H2S regulation. Antioxid. Redox Signal. 23, 129-147. [ABSTRACT FROM AUTHOR]

Neurogenic pulmonary edema caused by severe brainstem encephalitis is the leading cause of death in young children infected by Enterovirus 71 (EV71). However, no pulmonary lesions have been found in EV71-infected transgenic or non-transgenic mouse models. Development of a suitable animal model is important for studying EV71 pathogenesis and assessing effect of therapeutic approaches. We had found neurological disorders in EV71-induced young gerbils previously. Here, we report severe pulmonary lesions characterized with pulmonary congestion and hemorrhage in a gerbil model for EV71 infection. In the EV71-infected gerbils, six 21-day-old or younger gerbils presented with a sudden onset of symptoms and rapid illness progression after inoculation with 1×105.5 TCID50 of EV71 via intraperitoneal (IP) or intramuscular (IM) route. Respiratory symptoms were observed along with interstitial pneumonia, pulmonary congestion and extensive lung hemorrhage could be detected in the lung tissues by histopathological examination. EV71 viral titer was found to be peak at late stages of infection. EV71-induced pulmonary lesions, together with severe neurological disorders were also observed in gerbils, accurately mimicking the disease process in EV71-infected patients. Passive transfer with immune sera from EV71 infected adult gerbils with a neutralizing antibody (GMT=89) prevented severe pulmonary lesion formation after lethal EV71 challenge. These results establish this gerbil model as a useful platform for studying the pathogenesis of EV71-induced pulmonary lesions, immunotherapy and antiviral drugs. [ABSTRACT FROM AUTHOR]

The inherent speckle noise in medical ultrasound image degrades valuable clinical information and affects the diagnosis quality. Therefore, commercial ultrasound systems always face a big challenge to improve the visual quality of ultrasound images by reducing the speckle noise. A new hybrid algorithm is proposed in the present paper for speckle reduction by combining nonlinear coherence diffusion (NCD) with pyramid-transform-based multi-scale filters (named as Laplacian Pyramid Based Non-linear Coherence Diffusion; viz. LPNCD). The new approach exhibits good capability in preserving tissue features while enhancing the coherence. The theory and implementation of the approach are presented and verified based on phantom and clinical data. By comparing with previous techniques on quantified signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), the results suggest that the LPNCD method may demonstrate superior performance than other commonly used AD-class filters. Meanwhile, the performance of GPU implementations of the current technique is also evaluated, and it is verified that the LPNCD approach may have good performance efficiency and wonderful visual effect as running on mainstream commercial ultrasound systems. [ABSTRACT FROM AUTHOR]

In the present study, we investigated 21 short tandem repeat (STR) loci (D6S474, D12ATA63, D22S1045, D10S1248, D1S1677, D11S4463, D1S1627, D3S4529, D2S441, D6S1017, D4S2408, D19S433, D17S1301, D1GATA113, D18S853, D20S482, D14S1434, D9S1122, D2S1776, D10S1435, D5S2500), which are not included in the Combined DNA Index System and Amelogenin locus in 104 randomly selected healthy autochthonous individuals from the Tibetan ethnic minority group residing in the Lhasa region, Tibet Autonomous Region of China. Allelic frequencies, common forensic statistical parameters, and the Hardy-Weinberg equilibrium in this population were calculated with a modified PowerState V12.xls. A total of 143 alleles were found in the Tibetan group with corresponding allelic frequencies ranging from 0.005 to 0.582. The observed heterozygosity, the expected heterozygosity, the power of discrimination, the power of exclusion, and the polymorphic information content ranged from 0.615 to 0.817, 0.559 to 0.787, 0.727 to 0.926, 0.310 to 0.632, and 0.488 to 0.760, respectively. Chi-square tests of the observed genotype frequencies and expected genotype frequencies in the samples showed no departure from the Hardy-Weinberg equilibrium at all loci except for D5S2500. Our results demonstrate that these 21 STRs are highly polymorphic and suitable for anthropological research, population genetics, and forensic paternity testing and human individual identification in this region, and can enrich Chinese ethnical genetic informational resources. [ABSTRACT FROM AUTHOR]

The novel coronavirus pneumonia (COVID-19) pandemic is a great threat to human society and now is still spreading. Although several vaccines have been authorized for emergency use, only one recombinant subunit vaccine has been permitted for widespread use. More subunit vaccines for COVID-19 should be developed in the future. The receptor binding domain (RBD), located at the S protein of SARS-CoV-2, contains most of the neutralizing epitopes. However, the immunogenicity of RBD monomers is not strong enough. In this study, we fused the RBD-monomer with a modified Fc fragment of human IgG1 to form an RBD-Fc fusion protein. The recombinant vaccine candidate based on the RBD-Fc protein could induce high levels of IgG and neutralizing antibody in mice, and these could last for at least three months. The secretion of IFN-γ, IL-2 and IL-10 in the RBD-stimulated splenocytes of immunized mice also increased significantly. Our results first showed that the RBD-Fc vaccine could induce both humoral and cellular immune responses and might be an optional strategy to control COVID-19. [ABSTRACT FROM AUTHOR]

Amidst the global shortfalls in blood supply, storage limitations of donor blood and the availability of potential blood substitutes for transfusion applications, society has pivoted towards in vitro generation of red blood cells (RBCs) as a means to solve these issues. Many conventional research studies over the past few decades have found success in differentiating hematopoietic stem and progenitor cells (HSPCs) from cord blood, adult bone marrow and peripheral blood sources. More recently, techniques that involve immortalization of erythroblast sources have also gained traction in tackling this problem. However, the RBCs generated from human induced pluripotent stem cells (hiPSCs) still remain as the most favorable solution due to many of its added advantages. In this review, we focus on the breakthroughs for high-density cultures of hiPSC-derived RBCs, and highlight the major challenges and prospective solutions throughout the whole process of erythropoiesis for hiPSC-derived RBCs. Furthermore, we elaborate on the recent advances and techniques used to achieve cost-effective, high-density cultures of GMP-compliant RBCs, and on their relevant novel applications after downstream processing and purification. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two most important pathogens of hand, foot, and mouth disease (HFMD). However, the neuropathogenesis of EV71 and CVA16 has not been elucidated. In our previous study, we established gerbils as a useful model for both EV71 and CVA16 infection. In this work, we used RNA-seq technology to analyze the global gene expression of the brainstem of EV71- and CVA16-infected gerbils. We found that 3434 genes were upregulated while 916 genes were downregulated in EV71-infected gerbils. In CVA16-infected gerbils, 1039 genes were upregulated, and 299 genes were downregulated. We also found significant dysregulation of cytokines, such as IP-10 and CXCL9, in the brainstem of gerbils. The expression levels of 10 of the most upregulated genes were confirmed by real-time RT-PCR, and the upregulated tendency of most genes was in accordance with the differential gene expression (DGE) results. Our work provided global gene expression analysis of virus-infected gerbils and laid a solid foundation for elucidating the neuropathogenesis mechanisms of EV71 and CVA16. [ABSTRACT FROM AUTHOR]

Purpose: To establish a radiomics nomogram integrating clinical factors and radiomics features from ultrasound for the preoperative diagnosis axillary lymph node (ALN) status in patients with early-stage invasive breast cancer (EIBC).Materials and Methods: Between September 2016 and December 2018, four hundred twenty-six ultrasound manually segmented images of patients with EIBC were enrolled in our retrospective study, which were divided into a primary cohort (n = 300) and a validation cohort (n = 126). A radiomics signature was built with the least absolute shrinkage and selection operator (LASSO) algorithm in the primary cohort. Multivariable logistic regression analysis was used to establish a radiomics nomogram model based on radiomics signature and clinical variables. The performance of nomogram was quantified with respect to discrimination and calibration. The radiomics model was further evaluated in the internal validation cohort.Results: The radiomics signature, consisted of fourteen selected ALN-status-related features, achieved moderate prediction efficacy with an area under the curve (AUC) of 0.78 and 0.71 in the primary and validation cohorts respectively. The radiomics nomogram, comprising tumor size, US-reported LN status and radiomics signature, showed good calibration and favorite performance for ALN detection (AUC 0.84 and 0.81 in the primary and validation cohort). The decision curve which was demonstrated the radiomics nomogram displayed good clinical utility.Conclusion: The radiomics nomogram could hold promise as a non-invasive and reliable tool in predicting ALN metastasis and may facilitate to develop more effective preoperative decision-making. [ABSTRACT FROM AUTHOR]

Summary During development, neural stem cells (NSCs) undergo transitions from neuroepithelial cells to radial glial cells (RGCs), and later, a subpopulation of slowly dividing RGCs gives rise to the quiescent adult NSCs that populate the ventricular-subventricular zone (V-SVZ). Here we show that VCAM1, a transmembrane protein previously found in quiescent adult NSCs, is expressed by a subpopulation of embryonic RGCs, in a temporal and region-specific manner. Loss of VCAM1 reduced the number of active embryonic RGCs by stimulating their premature neuronal differentiation while preventing quiescence in the slowly dividing RGCs. This in turn diminished the embryonic origin of postnatal NSCs, resulting in loss of adult NSCs and defective V-SVZ regeneration. VCAM1 affects the NSC fate by signaling through its intracellular domain to regulate β-catenin signaling in a context-dependent manner. Our findings provide new insight on how stem cells in the embryo are preserved to meet the need for growth and regeneration. [ABSTRACT FROM AUTHOR]