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A rare but typically overlooked diagnosis in the orthopaedic surgery community is superior cluneal nerve (SCN) entrapment syndrome. The cluneal nerves function as purely sensory fibers, and the SCNs provide cutaneous innervation to the posterior parasacral, gluteal, and posterolateral thigh regions. When irritated, this syndrome can cause acute and chronic lower back pain and lower extremity symptoms. A 14-year-old adolescent girl presented to the clinic for an evaluation of pain in the right side of her lower back. The patient's physical examination showed tenderness to palpation on the right posterior iliac crest seven centimeters from the midline. Her neurologic examination demonstrated normal deep tendon reflexes, muscle strength, and sensation in the L2-S1 dermatomal distribution. Although imaging showed evidence of a left L5 spondylolysis, she responded positively to a steroid injection over the posterior iliac crest but negatively to one over the L5 pars defect. She later underwent a right SCN decompression surgery. After the procedure, she reported at least 90% improvement in her pain and rated it as a one in severity, on a scale of 0 to 10. Research regarding SCN entrapment syndrome has increased in the past several years. However, most of these studies are limited to the adult population. Therefore, more reports highlighting the potential for this syndrome in adolescents are needed as well., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Objective: During the Omicron wave of the COVID-19 pandemic in Shanghai, Fangcang Shelter Hospital (FSH) served as the major way in patient quarantine. Many COVID patients served as volunteers in FSH providing a lot of assistance for the medical workers and other COVID patients. The aim of this study was to explore the experiences of patient volunteers in FSH. It helps health professionals better understand their motivational incentives and barriers in their volunteer work, and improves recruiting and managing volunteers in subsequent public health emergencies., Methods: This is a qualitative study using semi-structured interviews. Thirteen patient volunteers working in an FSH in Shanghai were included. Thematic analysis was applied to data analysis., Results: Four themes and nine subthemes were identified. The wishes to give back to society and the responsibility of politics and religion were the main reasons for the patients to serve as volunteers in FSH. The patient volunteers served as the bridge to reduce the communication barriers between other patients and healthcare professionals. They also provided support in supply distribution and psychological counseling. They viewed voluntary work as a usual task and tried to solve the barriers in their work. In turn, the voluntary work brought them benefits in mental and physical health, as well as another chance for growth., Conclusion: Working as volunteers in FSHs not only brought personal benefits to the COVID patients but also fulfilled the needs of the healthcare system during public health emergencies. The mode of mutual help between patients could be taken as an example in other public health emergencies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Xu, Ruan, Huang and Cen.)

Background: Extreme temperature events, including extreme cold, are becoming more frequent worldwide, which might be harmful to pregnant women and cause adverse birth outcomes. We aimed to investigate the association between exposure to low ambient temperature in pregnant women and adverse birth outcomes, such as preterm birth, low birth weight, and stillbirth, and to summarize the evidence herein., Methods: Relevant studies were searched in PubMed, Cochrane, and Embase electronic databases until November 2021. Studies involving low ambient temperature, preterm birth, birth weight, and stillbirth were included. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed to conduct this study risk of bias and methods for data synthesis., Results: A total of 34 studies were included. First, pregnant women exposed to low ambient temperature had an increased risk of preterm birth (risk ratio [RR] 1.08; 95% confidence interval [CI] 1.04-1.13). Subgroup analyses revealed that exposure during late pregnancy was more likely to induce preterm birth. In addition, only pregnant women exposed to <1st percentile of the mean temperature suffered increased risk of preterm birth. Moreover, pregnant women living in medium or hot areas were more prone to have preterm births than those in cold areas when exposed to low ambient temperatures. Asians and Blacks were more susceptible to low ambient temperatures than Caucasians. Second, pregnant women exposed to low ambient temperature had an increased risk of low birth weight (RR 1.07; 95% CI 1.03-1.12). Third, pregnant women had an increased risk of stillbirth while exposed to low ambient temperature during the entire pregnancy (RR 4.63; 95% CI 3.99-5.38)., Conclusions: Exposure to low ambient temperature during pregnancy increases the risk of adverse birth outcomes. Pregnant women should avoid exposure to extremely low ambient temperature (<1st percentile of the mean temperature), especially in their late pregnancy. This study could provide clues for preventing adverse outcomes from meteorological factors., Registration: No. CRD42021259776 at PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ )., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objectives: This study aimed to review and summarize the studies of nurse-coordinated home-based cardiac rehabilitation for patients with heart failure., Methods: The review was performed using Arksey and O'Malley's scoping review framework. A systematic search was conducted across eight databases, including PubMed, Embase, Web of Science, EBSCO, China Biomedical Literature Service System (SinoMed), China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Science and Technology Journals (CSTJ) Database, and Chinese Clinical Trial Registry, from inception to 30 April 2023. Articles relevant to the nurse-coordinated home-based cardiac rehabilitation for patients with heart failure were included., Results: Eighteen studies were included in this review. These studies showed that nurses primarily focused on patient assessment, home-based cardiac rehabilitation planning and guidance, and follow-up. The studies also reported positive outcomes in patient safety, feasibility, and efficacy of the programs coordinated by nurses., Conclusions: Home-based cardiac rehabilitation coordinated by nurses is beneficial to patients with heart failure. Future research will explore the potential of nurses in home-based cardiac rehabilitation for patients with heart failure, determine optimal evaluation criteria, and formulate safe, effective, and economical rehabilitation programs suitable for the patients., Competing Interests: The authors have declared no conflict of interest., (© 2023 The Authors.)

Exposure to environmental organic pollutants has triggered significant ecological impacts and adverse health outcomes, which have been received substantial and increasing attention. The contribution of unidentified chemical components is considered as the most significant knowledge gap in understanding the combined effects of pollutant mixtures. To address this issue, remarkable analytical breakthroughs have recently been made. In this review, the basic principles on recognition of environmental organic pollutants are overviewed. Complementary analytical methodologies (i.e., quantitative structure-activity relationship prediction, mass spectrometric nontarget screening, and effect-directed analysis) and experimental platforms are briefly described. The stages of technique development and/or essential parts of the analytical workflow for each of the methodologies are then reviewed. Finally, plausible technique paths and applications of the future nontarget screening methods, interdisciplinary techniques for achieving toxicant identification, and burgeoning strategies on risk assessment of chemical cocktails are discussed.

Introduction: Amisulpride is primarily eliminated via the kidneys. Given the clear influence of renal clearance on plasma concentration, we aimed to explicitly examine the impact of renal function on amisulpride pharmacokinetics (PK) via population PK modelling and Monte Carlo simulations. Method: Plasma concentrations from 921 patients (776 in development and 145 in validation) were utilized. Results: Amisulpride PK could be described by a one-compartment model with linear elimination where estimated glomerular filtration rate, eGFR, had a significant influence on clearance. All PK parameters (estimate, RSE%) were precisely estimated: apparent volume of distribution (645 L, 18%), apparent clearance (60.5 L/h, 2%), absorption rate constant (0.106 h -1 , 12%) and coefficient of renal function on clearance (0.817, 10%). No other significant covariate was found. The predictive performance of the model was externally validated. Covariate analysis showed an inverse relationship between eGFR and exposure, where subjects with eGFR= 30 mL/min/1.73 m 2 had more than 2-fold increase in AUC, trough and peak concentration. Simulation results further illustrated that, given a dose of 800 mg, plasma concentrations of all patients with renal impairment would exceed 640 ng/mL. Discussion: Our work demonstrated the importance of renal function in amisulpride dose adjustment and provided a quantitative framework to guide individualized dosing for Chinese patients with schizophrenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Mak, Ruan, Dong, Zheng, Gu, Guo, Zhang, Cheng, Ruan, Shi, Zang, Zhu, He, Xiang, Wang and Zhu.)

Benzotriazole ultraviolet stabilizers (BZT-UVs), substituted diphenylamine antioxidants (S-DPAs), and synthetic phenolic antioxidants (SPAs) are three types of synthetic additive pollutants that are received increasing attention in the recent decade. In this study, a total of twenty-seven target analytes were measured in sediment cores and surface sediments collected from a lake with long sedimentary history. All target analytes were detected in the sediment samples, and mean values of the total ∑BZT-UVs, ∑S-DPAs and ∑SPAs concentrations were 220 ± 552 ng/g dry weight (d.w.), 20.8 ± 27.9 ng/g d. w., and 95.8 ± 146 ng/g d. w., respectively. Based on the dating results of two sediment cores, the total concentrations of BZT-UVs, S-DPA, and SPAs showed a fluctuating but overall increasing trend over time, which intuitively reflects the change of historical emissions. Meanwhile, fecal and sewage markers (i.e., sterols and pharmaceuticals, respectively) were jointly used to trace the probable sources of these pollutants. Results from the correlation and clustering analyses suggest that unregular fecal discharges and point-source domestic sewage need to be considered if pollution in the investigated area is to be controlled. To our knowledge, this study is the initial attempt to reveal the temporal variations of these synthetic additive pollutants in an aquatic environment in China and to demonstrate the feasibility of using markers to trace the sources of emerging pollutant analogues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Immune checkpoint inhibitors have achieved limited clinical effectiveness in colon cancer. Stem memory T cells (TSCMs) and in-situ cytotoxic T cells are dominant contributors to host immunity. Currently, data on the correlation between TSCM and T cell abundance and clinicopathological characteristics in colon cancer are largely unavailable., Methods: In-situ cytotoxic T cells are identified based on the quantification of CD3 + and CD8 + markers using immunohistochemistry (IHC) in the core of the tumor and the invasive margin of the tumor. The expression of representative markers of TSCMs, CD27 and CD95, was assayed using IHC in colon cancer tissues. Correlations between the levels of each marker and the clinicopathological characteristics as well as prognosis were evaluated., Results: High densities of CD3 + and CD8 + T cells correlated with stage I-II tumors, whereas a lower infiltration of cytotoxic T cells correlated with advanced-stage tumors. CD27 and CD95 were both expressed in the membrane of T cells present in the tumor stroma and their levels showed a negative correlation with the TNM stage. CD3, CD8, and CD27 were expressed at the same locations simultaneously, indicating their coordinated action against cancer. In addition, cytotoxic T cell densities and CD27 and CD95 expression remained independent prognostic factors for overall survival., Conclusion: In-situ cytotoxic T cells and TSCMs play important roles in colon cancer development. TSCMs marker CD27 and CD95 were both indicators of survival in patients with colon cancer. Thus, it is believed that TSCMs represent a desirable population for future use in combination immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ding et al.)

Obesity leads to the development of many metabolic diseases, causing severe health problems. Menthol can induce adipocyte browning and thus has been used to combat obesity. To deliver menthol with a sustained effect, an injectable hydrogel that comprises carboxymethyl chitosan and aldehyde-functionalized alginate that are crosslinked through dynamic Schiff-base linkages is developed to load menthol-cyclodextrin inclusion complexes (IC). To render the as-developed hydrogel soluble after its payload is released, amino acid-loaded liposomes, functioning as nanocontrollers, are covalently grafted onto networks of the hydrogel. Upon subcutaneous injection in mice with diet-induced obesity, the as-developed hydrogel absorbs body fluids and spontaneously swells, expanding and stretching its networks, gradually releasing the loaded IC. Menthol then disassociates from the released IC to induce adipocyte browning, triggering fat consumption and increasing energy expenditure. Meanwhile, the expanded hydrogel networks destabilize the grafted liposomes, which function as built-in nanocontrollers, unleashing their loaded amino acid molecules to disrupt the dynamic Schiff-base linkages, causing hydrogel to dissolve. The thus-developed nanocontroller-mediated dissolving hydrogel realizes the sustained release of menthol for treating obesity and its related metabolic disorders without leaving exogenous hydrogel materials inside the body, and thereby preventing any undesired adverse effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Solar power generation in Sweden is far from required capacity to help with transition towards 100% renewables in the power sector by 2040. Decentralized PV system attracts attentions given the conflicts of future increasing demands and land scarcity in the urban areas. However, it is not easy to implement it due to challenges on local conditions and lack of references. This paper aims to propose an overview of the potential of small-scale grid-connected PV systems in a Swedish context and offer an example for urban PV system planning in Sweden or high latitude areas. A model considering weather, space, infrastructures and economics is developed and implemented with a real case in the Swedish context. The findings verify the technical and economic feasibility of urban decentralized rooftop PV systems in the Swedish context. It is found that this kind of system does have considerable power potential in the Swedish context without land requirements. This kind of PV system could be a promising option for future power generation which satisfies part of demands and reduces pressure on external grids. The full potential could be only achieved with improved infrastructures, and the profitability of the system relies heavily on market and political conditions. This study can be a refence for other high latitude areas., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Motivation: Biomedical relation extraction is a vital task for electronic health record mining and biomedical knowledge base construction. Previous work often adopts pipeline methods or joint methods to extract subject, relation, and object while ignoring the interaction of subject-object entity pair and relation within the triplet structure. However, we observe that entity pair and relation within a triplet are highly related, which motivates us to build a framework to extract triplets that can capture the rich interactions among the elements in a triplet., Results: We propose a novel co-adaptive biomedical relation extraction framework based on a duality-aware mechanism. This framework is designed as a bidirectional extraction structure that fully takes interdependence into account in the duality-aware extraction process of subject-object entity pair and relation. Based on the framework, we design a co-adaptive training strategy and a co-adaptive tuning algorithm as collaborative optimization methods between modules to promote better mining framework performance gain. The experiments on two public datasets show that our method achieves the best F1 among all state-of-the-art baselines and provides strong performance gain on complex scenarios of various overlapping patterns, multiple triplets, and cross-sentence triplets., Availability and Implementation: Code is available at https://github.com/11101028/CADA-BioRE., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Prophylactic antibiotic administration has been used to reduce infectious morbidities in cesarean deliveries. However, no consensus on the timing has been reached. We performed this review to compare maternal and neonatal infectious morbidities of antibiotic administration before skin incision and after cord clamping. Methods: PubMed, EMBASE, MEDLINE, Cochrane Library, and Web of Science databases were searched. Only randomized controlled trials (RCTs) comparing the use of antibiotic agents pre-operatively and after cord clamping were included. Characteristics and results of the included studies were extracted, and risks of bias were assessed. A fixed-effect model was applied to estimate the relative risks (RRs) for outcomes. Results: Sixteen RCTs, including 8,027 women and 7,131 newborns, met the selection criteria. Pre-operative administration of antibiotic agents was associated with a reduction in the risk of endometritis (RR, 0.52; 95% confidence interval [CI], 0.37-0.72) and wound complications (RR, 0.54; 95% CI, 0.42-0.69), compared with administration after cord clamping. No differences were observed in the rate of febrile illness (RR, 0.79; 95% CI, 0.59-1.05), urinary tract infection (RR, 0.92; 95% CI, 0.64-1.32), neonatal intensive care unit (NICU) admission (RR, 0.94; 95% CI, 0.79-1.12), and neonatal sepsis (RR, 0.83; 95% CI, 0.61-1.14). Conclusions: The present study showed that prophylactic antibiotic agent administration before skin incision can reduce the risk of endometritis and wound complications while not increasing that of NICU admission and neonatal sepsis compared with administration after cord clamping.

To explore the versatility of speakers, a piezoelectric micro-electro-mechanical system (MEMS) speaker combining the function of a silent alarm is proposed, which mainly comprises a lead zirconate titanate (PZT) actuation layer and a rigid-flexible coupling supporting layer. Measurements performed on encapsulated prototypes mounted to an artificial ear simulator have revealed that, compared to a speaker with a rigid supporting layer, the sound pressure level (SPL) of the proposed piezoelectric MEMS speaker with a rigid-flexible coupling supporting layer is significantly higher and is especially higher by 4.1-20.1 dB in the frequency range from 20 Hz to 4.2 kHz, indicating that the rigid-flexible coupling supporting layer can improve the SPL significantly in low frequency. Moreover, the spectral distribution characteristic of its playback audio is similar to that of the commercial electromagnetic type. The device can also function as a silent alarm based on oral airflows in dangerous situations, as it performs well at recognizing words according to their unique voltage-signal characteristics, and can avoid the effects of external sound noise, body movement, long distance, and occlusion. This strategy provides inspiration for functional diversification of piezoelectric MEMS speakers.

Introduction: Male infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP70 in human male infertility is limited., Methods: Whole exome sequencing and Sanger sequencing were used to identify the genetic cause of the infertile patients. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy were further conducted to explore morphological and ultrastructural defects in spermatozoa from the patient. Immunofluorescence staining was used to detect the pathogenicity of the identified variants and the particular expression of CEP70 in testis., Results: In this study, we identified biallelic mutations of CEP70 in two unrelated infertile male individuals with oligoasthenoteratozoospermia that followed a recessive inheritance pattern. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy showed that morphological and ultrastructural defects in the acrosome and flagellum of sperm from the patient in a pattern strikingly similar to that in Cep70 -/- male mice. The results of immunofluorescence staining suggested that CEP70 was normally expressed in the acrosome and flagellum of control sperm but was hardly detected in the sperm of patient carrying CEP70 variation. We also explored the particular expression pattern of CEP70 during spermatogenesis in humans and mice., Conclusions: Biallelic mutations of CEP70 might be a novel genetic cause of human male infertility, which could potentially serve as a basis for genetic counseling and diagnosis of male infertility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ruan, Yang, Jiang, Shen, Li and Shen.)

In recent years, relation extraction on unstructured texts has become an important task in medical research. However, relation extraction requires a large amount of labeled corpus, manually annotating sequences is time consuming and expensive. Therefore, efficient and economical methods for annotating sequences are required to ensure the performance of relational extraction. This paper proposes a method of subsequence and distant supervision based active learning. The method is annotated by selecting information-rich subsequences as a sampling unit instead of the full sentences in traditional active learning. Additionally, the method saves the labeled subsequence texts and their corresponding labels in a dictionary which is continuously updated and maintained, and pre-labels the unlabeled set through text matching based on the idea of distant supervision. Finally, the method combines a Chinese-RoBERTa-CRF model for relation extraction in Chinese medical texts. Experimental results test on the CMeIE dataset achieves the best performance compared to existing methods. And the best F1 value obtained between different sampling strategies is 55.96%., (© 2023. The Author(s).)

Objective: The aim of this study is to establish a suitable animal model of chronic kidney disease-mineral and bone disorder (CKD-MBD) by comparing CKD-MBD rat models induced by 5/6 Nx, AN, and UUO, accompanied by a low-calcium and high-phosphorus diet. Methods: Sprague‒Dawley rats were randomly divided into four groups: control group, 5/6 nephrectomy (5/6 Nx) group, Adriamycin nephropathy (AN) group, and unilateral ureteral obstruction (UUO) group. Serum biochemical indices were measured to evaluate renal function, mineral and bone metabolism, the severity of CKD-MBD, and the status of bone transformation. Hematoxylin-eosin staining (HE) and Masson's trichrome (Masson) staining were used for histopathological analysis of the kidney. Goldner's trichrome (Goldner) and tartrate-resistant acid phosphatase (TRAP) staining were utilized to observe bone mineralization and osteoclasts in the femur, respectively. Micro-CT images were applied to study the structure of the femur. The expression levels of osterix and cathepsin K in the femur were measured by immunohistochemistry (IHC) to confirm the status of bone transformation. Results: The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in the 5/6 Nx and AN group rats were significantly higher than those in the control rats, and this change was accompanied by marked changes in the levels of calcium (Ca), phosphate (Pi), intact parathyroid hormone (i-PTH), fibroblast growth factor 23 (FGF23), osteocalcin (OC), and cross-linked C-telopeptide of type 1 collagen (CTX-1); UUO group rats exhibited slight and inconsistent variations in the levels of Scr, BUN, Ca, Pi, i-PTH, FGF23, OC, and CTX-1 in serum. Histopathological analysis of the kidney showed that the UUO group rats suffered serious fibrosis and 5/6 Nx group rats exhibited severe focal calcification. Histopathological analysis of the femur showed that the AN group rats had minimal bone mineralization and that the 5/6 Nx group rats had overactive osteoclasts. Micro-CT revealed that the AN model had the most severe bone destruction and that the 5/6 Nx model had the least severe bone loss among the three models. The expression of cathepsin K in the femur was significantly increased in all models, while the expression of osterix in the femur was only significantly increased in the 5/6 Nx model. Conclusion: 5/6 Nx, AN, and UUO accompanied by a low-calcium and high-phosphorus diet successfully induced CKD-MBD in rats. The 5/6 N X model presented the progression of high-turnover bone disease, with consistency between biochemical indices in serum and histomorphometric analysis of the femur, and the AN and UUO models developed a severe deterioration in bone quantity and severe bone resorption; however, the changes in biochemical indices were subtle in the UUO model, and liver injury was obvious in the AN model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Li, Wang, Li, Ruan, Guo, Wang and Meng.)

Medical image segmentation is an essential task in clinical diagnosis and case analysis. Most of the existing methods are based on U-shaped convolutional neural networks (CNNs), and one of disadvantages is that the long-term dependencies and global contextual connections cannot be effectively established, which results in inaccuracy segmentation. For fully using low-level features to enhance global features and reduce the semantic gap between encoding and decoding stages, we propose a novel Swin Transformer boosted U-Net (ST-Unet) for medical image processing in this paper, in which Swin Transformer and CNNs are used as encoder and decoder respectively. Then a novel Cross-Layer Feature Enhancement (CLFE) module is proposed to realize cross-layer feature learning, and a Spatial and Channel Squeeze & Excitation module is adopted to highlight the saliency of specific regions. Finally, we learn the features fused by the CLFE module through CNNs to recover low-level features and localize local features for realizing more accurate semantic segmentation. Experiments on widely used public datasets Synapse and ISIC 2018 prove that our proposed ST-Unet can achieve 78.86 of dice and 0.9243 of recall performance, outperforming most current medical image segmentation methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) in T4 colorectal cancer (CRC) remains controversial. The study aimed to explore the safety and efficacy of radical surgery (RS) with HIPEC in T4 CRC., Methods: Adverse events after HIPEC were estimated by Common Terminology Criteria for Adverse Events version 5.0. The efficacy was evaluated using recurrence-free survival (RFS) and overall survival (OS). Propensity score matching (PSM) was used to reduce the effects of confounders between groups., Results: Of the 417 patients (263 men and 154 women), 165 patients were treated with RS + HIPEC and 252 patients with RS alone. There was no significant difference in the incidence of all adverse events after PSM. Overall RFS and OS were not significantly different at 24 months ( p = 0.580 and p = 0.072, respectively). However, in patients with T4b stage CRC (92.1% vs. 77.3%, p = 0.048) and tumor size ≥ 5 cm (93.0% vs. 80.9%, p = 0.029), RFS in the two groups showed a significant difference at 24 months., Conclusions: In summary, the safety of HIPEC in T4 CRC was confirmed. Compared with RS, though RS + HIPEC did not benefit the overall cohort at 24 months, RS + HIPEC could benefit patients with T4b stage CRC and tumor size ≥ 5 cm in RFS.

Background: The drug selection of radical surgery (RS), with hyperthermic intraperitoneal chemotherapy (HIPEC), in pT4 colorectal cancer (CRC) remains controversial., Methods: Adverse events after HIPEC were estimated by common terminology criteria for adverse events version 5.0. The efficacy was evaluated using overall survival (OS) and recurrence-free rate (RFR). Propensity score matching (PSM) was used to reduce the influence of confounders between Mitomycin and Lobaplatin groups., Results: Of the 146 patients, from April 2020 to March 2021, 47 were managed with mitomycin and 99 with lobaplatin. There was no significant difference in the incidence of all adverse events between the two groups after PSM. OS and RFR were not significantly different between the two groups at 22 months ( p = 0.410; p = 0.310). OS and RFR of the two groups also showed no significant difference for patients with T4a or T4b stage, tumor size < or ≥ 5 cm. Among patients with colon cancer, RFR at 22 months of the two groups was significantly different (100.0% vs. 63.2%, p = 0.028)., Conclusions: In summary, the safety of mitomycin and lobaplatin for HIPEC was not different. Compared with lobaplatin, mitomycin for HIPEC after RS could benefit patients with colon cancer in RFR.

Background: Circular RNAs (circRNAs) are endogenous noncoding RNAs that play vital roles in many biological processes, particularly in human cancer. Recent studies indicate that circRNAs play an important role in tumor progression through exosomes. However, the specific functions of gastric cancer-derived exosomes and the role of circSTAU2 in gastric cancer (GC) remain largely unknown., Methods: Differentially expressed circRNAs in GC were identified by circRNA microarrays analysis and quantitative real-time polymerase chain reaction (qRT-PCR). The role of circSTAU2 in GC was verified by circSTAU2 knockdown and overexpression with functional assays both in vitro and in vivo. Fluorescence in situ hybridization (FISH), immunofluorescence, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, qRT-PCR and Western blot were adopted to evaluate the expression and regulatory mechanism of MBNL1, circSTAU2, miR-589 and CAPZA1. Furthermore, the role of exosomes was demonstrated by transmission electron microscopy and nano-sight particle tracking analysis., Results: CircSTAU2, mainly localized in the cytoplasm, was significantly downregulated in GC. CircSTAU2 overexpression inhibited GC cell proliferation, invasion and migration both in vitro and in vivo, while circSTAU2 knockdown had the inverse effect. CircSTAU2 could be wrapped in exosomes and delivered to recipient cells, and functioned as a sponge for miR-589 to relieve its inhibitory effect on CAPZA1, thus inhibiting GC progression. Furthermore, MBNL1 acted as the upstream RNA-binding protein of circSTAU2 and significantly influenced the circularization and expression of circSTAU2., Conclusion: Exosome-delivered circSTAU2 may act as a tumor suppressor that restrains GC progression via miR-589/CAPZA1 axis, which demonstrates a potential therapeutic target for GC., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Zhang et al.)

Abnormal metabolism is a hallmark of cancer cells. Accumulating evidence suggests that metabolic changes are likely to occur before other cellular responses in cancer cells upon drug treatment. Therefore, the metabolic activity or flux in cancer cells could be a potent biomarker for cancer detection and treatment monitoring. Magnetic resonance (MR)-based sensing technologies have been developed with hyperpolarized molecules for real-time flux analysis, but they still suffer from low sensitivity and throughput. To address this limitation, we have developed an innovative miniaturized MR coil, termed micro-slab MR coil, for simultaneous analysis of metabolic flux in multiple samples. Combining this approach with hyperpolarized probes, we were able to quantify the pyruvate-to-lactate flux in two different leukemic cell lines in a non-destructive manner, simultaneously. Further, we were able to rapidly assess flux changes with drug treatment in a single hyperpolarization experiment. This new multi-sample system has the potential to transform our ability to assess metabolic dynamics at scale.

The study aimed to investigate the effect of flywheel accentuated eccentric loading (AEL) training on the running economy (RE) of young male well-trained distance runners. Twenty-two runners participated and were randomly assigned to the flywheel (FG, n = 12) and the control group (CG, n = 10). Traditional endurance training was performed in both groups three times a week for 6-week, while traditional resistance and flywheel AEL training was added to the CG and FG respectively. Subjects performed the incremental exercise test, squat jump, and countermovement jump (CMJ) before and after training. The results showed that 1) the RE at 65% of peak oxygen consumption (VO 2 peak), 75% VO 2 peak, and 85% VO 2 peak improved significantly after 6 weeks of training ( p < 0.01, Effect size (ES) = 0.76; p < 0.01, ES = 1.04; p < 0.01, ES = 1.85) in FG, and the RE of 85% VO 2 peak in FG was significantly lower than CG ( p < 0.05, ES = 0.30); 2) in post-training, both squat jump ( p < 0.01, ES = 0.73) and CMJ ( p < 0.01, ES = 1.15) performance, eccentric utilization ratio ( p < 0.04, ES = 0.44), the rate of force development (RFD) of squat jump ( p < 0.05, ES = 0.46), and CMJ RFD ( p < 0.01, ES = 0.66) were significantly improved in FG. And there are no significant differents in CG group because it was maintain training for our participants. Our findings showed that 1) flywheel AEL training improves the muscles' explosive strength and other neuromuscular functions, and improves the athlete's running economy under 65%, 75%, and 85% VO 2 peak, which potentially increases endurance performance. 2) Flywheel AEL training can improve the height, RFD, and the eccentric utilization ratio of squat jump and CMJ, and other lower limb elastic potential energy indicators of the young male, well-trained distance runners., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Weng, Liu, Ruan, Yang, Wei, Cui, Ho and Li.)

Centrosomal protein 120 (CEP120) is a 120 kDa centrosome protein that plays an important role in centrosome replication. Overexpression of CEP120 can lead to centrosome duplicate abnormality, which is closely associated with tumorigenesis and development. However, there are no reports on the relationship between CEP120 and tumors. In our study, overexpression of CEP120 promoted centrosome amplification in gastric cancer (GC), and the role of CEP120 in promoting GC progression was demonstrated in vitro and in vivo . We demonstrated that CEP120 promotes centrosome amplification and GC progression by promoting the expression and centrosome aggregation of the deubiquitinating enzyme USP54, maintaining the stability of PLK4 and reducing its ubiquitination degradation. In conclusion, the CEP120-USP54-PLK4 axis may play an important role in promoting centrosome amplification and GC progression, thus providing a potential therapeutic target for GC., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Benzotriazole UV stabilizers (BZT-UVs), including 2-(3,5-di- tert -amyl-2-hydroxyphenyl)benzotriazole (UV-328) that is currently under consideration for listing under the Stockholm Convention, are applied in many commodities and industrial products. However, limited information is available on the interannual variation of their environmental occurrence. In this study, an all-in-one strategy combining target, suspect, and nontarget screening analysis was established to comprehensively explore the temporal trends of BZT-UVs in mollusks collected from the Chinese Bohai Sea between 2010 and 2018. Significant residue levels of the target analytes were determined with a maximum total concentration of 6.4 × 10 3 ng/g dry weight. 2-(2-Hydroxy-3- tert -butyl-5-methyl-phenyl)-5-chloro-benzotriazole (UV-326), 5-chloro-2-(3,5-di- tert -butyl-2-hydroxyphenyl)benzotriazole (UV-327), and 2-(2-hydroxy-5-methylphenyl) benzotriazole (UV-P) were the predominant analogues, and UV-328 was the most frequently detected BZT-UV with a detection frequency (DF) of 87%. Whereas five biotransformation products and six impurity-like BZT-UVs were tentatively identified, their low DFs and semi-quantified concentrations suggest that the targeted analytes were the predominant BZT-UVs in the investigated area. A gradual decrease in the total concentrations of BZT-UVs was observed, accompanied by downward trends of the abundant compounds (e.g., UV-326 and UV-P). Consequently, the relative abundance of UV-327 increased because of its consistent environmental presence. These results suggest that continuous monitoring and risk assessment of BZT-UVs other than UV-328 are of importance in China.

Background: To explore the prognostic factors of survival in non-small cell lung cancer (NSCLC) patients using the competing risk analysis., Methods: This was a retrospective cohort study. NSCLC patients with complete data were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Outcomes were censored, cancer-specific mortality in NSCLC, and other-cause mortality. Gray's test was used in univariable analysis, and a multivariable Fine-Gray competing risk model with backward elimination was used to explore the prognostic factors of survival. The screened variables were incorporated into a random survival forest (RSF) model for the prediction of 1-, 3-, and 5-year survival in patients with NSCLC. Receiver operator characteristic (ROC) curves, calibration curves, the value of area under the curve (AUC), and decision curve analysis (DCA) were used to evaluate the performance., Results: Totally 1,251 eligible patients were included, 678 (54.20%) patients were cancer-specific mortality, and 128 (10.23%) patients were other-cause mortality. The median follow-up time was 26 months. Age, primary site, N stage, M stage, surgery type, tumor size, and lymph nodes (LNs) count were included in the multivariable Fine-Gray model for further analysis (P<0.05). The six most important features (surgery type, tumor size, M stage, LNs count, N stage, and primary site) were included in the competing risk analysis using the RSF model. The value of AUC for predicting 1-, 3-, and 5-year survival in the testing set were 0.796, 0.804, and 0.792, respectively. Calibration curves were well-fitted. DCA curves showed that the RSF model had similar or greater clinical net benefits in survival compared with the 8th edition the American Joint Committee on Cancer (AJCC) staging. The good performance of the RSF model under different surgery types, T, N, and M stages., Conclusions: We conducted a competing risk analysis using the RSF model for predicting the 1-, 3-, and 5-year survival of NSCLC. We generated a web calculator (https://github.com/YingChen19/Prognostic-factors-of-long-term-survival-of-non-small-cell-lung-cancer), which could provide a convenient assessment and could help improve the prognosis and survival of NSCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-21-2114/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Background: Mycoplasma pneumoniae (M. Pneumoniae ) is a common pathogen of respiratory tract infections, but there is still a lack of detailed investigation on the large sample of M. Pneumoniae infection in the all age population. And patients with severe M. Pneumoniae pneumonia (SMPP) still have a certain risk of death. How to identify the clinical characteristics and population of patients with SMPP as soon as possible is still an urgent problem in clinical practice., Methods: Demographic characteristics, patient clinical information, and laboratory data of 81,131 patients with respiratory tract infections (RTIs) in the Affiliated Suzhou Hospital of Nanjing Medical University from 2014 to 2020 were retrospectively collected from all patient records. The serum particle agglutination (PA) test was used to determine M. Pneumoniae infection by detecting specific antibodies. The white blood cell count, the proportion of neutrophils and lymphocytes, C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels between children and adults with SMPP were compared by Student's t -test; other clinical features were analyzed by χ 2 test or Fisher's exact test., Results: A total of 81,131 patients with RTIs were included, and 21,582 (26.60%) M. Pneumoniae immunoglobulin M (IgM)-positive patients were detected. From 2014 to 2020, the annual proportions of M. Pneumoniae RTIs were 23.60%, 28.18%, 38.08%, 27.05%, 23.44%, 25.26%, and 18.33%, respectively. In terms of seasonal distribution, April-June and September-November were the peak seasons of M. Pneumoniae infection each year. Children and women have a high proportion of M. Pneumoniae infection. The peak age of M. Pneumoniae infection was between 4 and 14 years old. There were 301 cases of SMPP, including 281 children and 20 adults (8 cases of pregnant women). Children and pregnant women accounted for a high proportion of SMPP. Children with SMPP had more extrapulmonary symptoms, multilobar infiltrates, and increased CRP and LDH levels compared with adults., Conclusions: M. Pneumoniae infection has seasonal, sex, and age distribution trends. Children and pregnant women accounted for a high proportion of SMPP. Extrapulmonary symptoms, multilobar infiltrates, and increased CRP and LDH levels may be helpful to identify SMPP in children than in adults., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4304/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Coherent modulation imaging (CMI) is a lessness diffraction imaging technique, which uses an iterative algorithm to reconstruct a complex field from a single intensity diffraction pattern. Deep learning as a powerful optimization method can be used to solve highly ill-conditioned problems, including complex field phase retrieval. In this study, a physics-driven neural network for CMI is developed, termed CMINet, to reconstruct the complex-valued object from a single diffraction pattern. The developed approach optimizes the network's weights by a customized physical-model-based loss function, instead of using any ground truth of the reconstructed object for training beforehand. Simulation experiment results show that the developed CMINet has a high reconstruction quality with less noise and robustness to physical parameters. Besides, a trained CMINet can be used to reconstruct a dynamic process with a fast speed instead of iterations frame-by-frame. The biological experiment results show that CMINet can reconstruct high-quality amplitude and phase images with more sharp details, which is practical for biological imaging applications.

Stress from mixtures of synthetic chemicals is among the key issues that have significant adverse impacts on the marine ecosystems. A robust screening workflow integrating toxicological-based ranking schemes is still deficient for comprehensive investigation on the main constituents in chemical mixtures that contribute to the ecological risks. In this study, the presence and compositions of a collection of priority pollutants were monitored by suspect screening analysis of seawater and estuarine water samples from the semiclosed Bohai Sea. In total, 108 organic pollutants in nine use categories were identified. Pesticides, intermediates, plastic additives, and per- and polyfluoroalkyl substances were the extensively detected chemical groups. Varied distribution patterns of the pollutants were illustrated intuitively in distinctive sampling areas by hierarchical cluster analysis, which were mainly influenced by run-off inputs, ocean currents, and chemical use history. Ecological risks of chemicals with quantified residue levels were first assessed by the toxicity-weighted concentration ranking scheme, and pentachlorophenol was found as the main contributor in the investigating areas. By optimization of multiple alternative variables (e.g., instrumental response and detection frequency), extended ranking of all the identified pollutants was plausible under the toxicological priority index framework. Similarity in toxicological endpoints of the prioritized pollutants could further been screened by ToxAlerts. Aromatic amine was highlighted as the most frequently detected structural alert (SA) for genotoxic carcinogenicity and mutagenicity. These findings fully demonstrate rationality of the ranking schemes integrated into the suspect screening analysis for profiling contamination characteristics, assessing ecological risk potentials, and prioritizing SAs.

Diverse nitrogen-containing organics are important components of humic-like substances (HULIS) in the atmosphere. In this study, organic components in particulate matter (PM) samples representing multiple sources were separated by successive solvent fractionation, which were then analyzed by mass spectrometric and optical instruments. The CHON compounds were eluted and clustered into the Low-polar, Medium-polar, and High-polar fractions, and discrepancies of the polar-fractions were particularly reflected by molecular descriptors such as aromaticity, oxygen content and molecular weight. In addition, the results from the light-absorbing parameters (i.e., MAE 365 and SUVA 254 ) underscored the importance of the Low-polar and High-polar fractions on optical absorption properties. The Low-polar fraction accounted for 40% of the cumulative SUVA 254 values, suggesting significant content of ultraviolet-absorbing organics. The High-polar fraction contributed 52% of the cumulative MAE 365 values, indicating abundant light absorption capacity and efficiency. Significant improvements were made on statistical analysis of multidimensional data by a combination of the molecular descriptors and optical parameters. Molecular structures, including condensed aromatic, lignin-like, and aliphatic compounds observed in distinct electrospray ionization modes, were found as main contributors to the light absorption capacity and the abundances of fluorophores in individual polar-fractions. Differential contributions of molecular characteristics on types and abundances of fluorophores were further found among the samples of multiple sources. Conclusions obtained from this successive solvent fractionation experiment could promote development of the pretreatment method for exploring the potential light-absorbing organics, which also provide insights into the emission sources of organics that are related to specific light absorption and fluorescence properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has aroused public concerns as it can pose multiple health threats to pregnant women and cause adverse birth outcomes for fetuses. In previous studies, the prenatal exposure levels and transplacental transfer efficiencies (TTE) of PFASs have been reported and discussed. Specifically, the binding affinities between PFASs and some transporters were determined, demonstrating that the TTE values of PFASs are highly dependent on their binding behaviors. To summarize primary findings of previous studies and propose potential guidance for future research, this article provides a systematic overview on levels and characteristics of prenatal exposure to PFASs worldwide, summarizes relationships between TTE values and structures of PFASs, and discusses possible transplacental transfer mechanisms, especially for the combination between PFASs and transporters. Given the critical roles of transporters in the transplacental transfer of PFASs, we conducted molecular docking to further clarify the binding behaviors between PFASs and the selected transporters. We proposed that the machine learning can be a superior method to predict and reveal behaviors and mechanisms of the transplacental transfer of PFASs. In total, this is the first review providing a comprehensive overview on the prenatal exposure levels and transplacental transfer mechanisms of PFASs.

Purpose: The International Association for the Study of Lung Cancer (IASLC) of TNM staging system has been well accepted as a precise model. However, the latest American Joint Committee on Cancer (AJCC) staging system to solve the different survival and prognosis of lung adenocarcinoma in the same period is still controversial. Therefore, it is necessary to thoroughly explore the applicability between the new system and survival prediction in terms of lung adenocarcinoma., Methods: We recruited 52,517 patients with lung adenocarcinoma from the Surveillence, Epidemiology, and End Results database. Cox regression analysis was performed to determine survival related factors. The mortality rate per 1000 persons per year of the T4N2M0 lung adenocarcinoma stage and other stages were compared. Survival curves were obtained using the Kaplan-Meier analysis and log-rank test., Results: The results of Cox proportional hazards regression analysis showed that age at diagnosis, race, T stage, distant metastasis, extrathoracic extension, radiotherapy, chemotherapy, and surgery are independent factors related to cancer-specific survival (CSS) and all-cause survival. Furthermore, patients with stage IIIA disease (P<0.001) and IIIB disease (P<0.001) excluding stage at T4N2M0 had a significantly lower risk of CSS and all-cause survival than those staged with T4N2M0 disease. The mortality rates per 1000 person-years with patients staged at T4N2M0 lung adenocarcinoma had higher mortality than patients in the same period. The CSS curves of patients with stage T4N2M0 reflected an obvious decline compared with those of stages IIIA disease and IIIB excluding T4N2M0, and there is no significant difference between this curve and stage IIIC patients (P>0.05)., Conclusion: The survival rate of patients with T4N2M0 stage was significantly lower than that of patients with IIIA and IIIB stages excluding T4N2M0, there was no significant difference between T4N2M0 and IIIC. It was suggested that this group of patients with stage T4N2M0 were upgraded in the 8th IASLC system., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Piezoelectric arterial pulse wave dynamics are traditionally considered to be similar to those of typical blood pressure waves. However, achieving accurate continuous blood pressure wave monitoring based on arterial pulse waves remains challenging, because the correlation between piezoelectric pulse waves and their related blood pressure waves is unclear. To address this, the correlation between piezoelectric pulse waves and blood pressure waves is first elucidated via theoretical, simulation, and experimental analysis of these dynamics. Based on this correlation, the authors develop a wireless wearable continuous blood pressure monitoring system, with better portability than conventional systems that are based on the pulse wave velocity between multiple sensors. They explore the feasibility of achieving wearable continuous blood pressure monitoring without motion artifacts, using a single piezoelectric sensor. These findings eliminate the controversy over the arterial pulse wave piezoelectric response, and can potentially be used to develop a portable wearable continuous blood pressure monitoring device for the early prevention and daily control of hypertension., (© 2022 Wiley-VCH GmbH.)

As a lensless imaging technique, ptychography provides a new way to resolve the conflict between the spatial resolution and the field of view. However, due to the pixel size limit of the sensor, a compromise has to be reached between the spatial resolution and the signal-to-noise ratio. Here, we propose a resolution-enhanced ptychography framework with equivalent upsampling and subpixel accuracy in position to further improve the resolution of ptychography. According to the theory of pixel superresolved techniques, the inherent shift illumination scheme in ptychography can additionally enhance the resolution with the redundant data. An additional layer of pooling is used to simulate the downsampling of a digital record, and the pixel superresolved problem is transformed into an automatic optimization problem. The proposed framework is verified by optical experiments, both in biological samples and the resolution targets. Compared to the traditional algorithm, the spatial lateral resolution is twice as large using the same data set.

Mechanosensitive vagal afferents in the lung, rapidly and slowly adapting receptors (RARs and SARs, respectively), play an important role in eliciting the reflexes that regulate the normal airway function. A profound bronchoconstrictive effect of 5-hydroxytryptamine (5-HT) has been extensively reported in various animal species, but its influence on the SAR and RAR activity is not known. This study investigated the effect of 5-HT on these receptors, and the possible mechanisms involved. Single-fiber activities of these afferents were measured in anesthetized, open-chest, and mechanically ventilated rats. Our results showed that intravenous injection of 5-HT evoked a consistent and pronounced stimulation of phasic RARs. In contrast, 5-HT generated an inconsistent and paradoxical action on SARs: no effect in 29% (5 of 17) of the SARs; stimulation in 35% (6 of 17); and inhibition in the remainder. These responses of both RARs and SARs to 5-HT were reproducible and dose-dependent. After the injection of a high dose of 5-HT (16 μg/kg), the receptor responses slowly reached a peak (after ∼8 s) and returned toward the baseline in ∼20 s, accompanied by a consistent increase in total pulmonary resistance and a decrease in dynamic lung compliance in a temporal pattern very similar to the increased receptor activity. When these changes in lung mechanics induced by 5-HT were prevented by pretreatment with salbutamol, a β 2 adrenergic receptor agonist, the delayed responses of both RARs and SARs to 5-HT were also abolished, except that the immediate stimulatory effect on a subset of RARs, the silent RARs, was not affected. In conclusion, 5-HT generated a delayed stimulatory effect on RARs and a paradoxical effect on SARs, which resulted primarily from the 5-HT-induced changes in mechanical properties of the lung., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Hsu, Ruan and Lee.)

Skeletal muscle weakness is linked to many adverse health outcomes. Current research to identify new drugs has often been inconclusive due to lack of adequate cellular models. We previously developed a scalable monolayer system to differentiate human embryonic stem cells (hESCs) into mature skeletal muscle cells (SkMCs) within 26 days without cell sorting or genetic manipulation. Here, building on our previous work, we show that differentiation and fusion of myotubes can be further enhanced using the anabolic factors testosterone (T) and follistatin (F) in combination with a cocktail of myokines (C). Importantly, combined TFC treatment significantly enhanced both the hESC-SkMC fusion index and the expression levels of various skeletal muscle markers, including the motor protein myosin heavy chain (MyHC). Transcriptomic and proteomic analysis revealed oxidative phosphorylation as the most up-regulated pathway, and a significantly higher level of ATP and increased mitochondrial mass were also observed in TFC-treated hESC-SkMCs, suggesting enhanced energy metabolism is coupled with improved muscle differentiation. This cellular model will be a powerful tool for studying in vitro myogenesis and for drug discovery pertaining to further enhancing muscle development or treating muscle diseases.

Brain and muscle aryl-hydrocarbon receptor nuclear translocator like protein1 ( BMAL1 ), a core component of circadian oscillation, is involved in many physiological activities. Increasing evidence has demonstrated the essential role of BMAL1 in reproductive physiology. For instance, BMAL1 -knockout (KO) mice were infertile, with impaired reproductive organs and gametes. Additionally, in BMAL1 -KO mice, hormone secretion and signaling of hypothalamus-pituitary-gonadal (H-P-G) hormones were also disrupted, indicating that H-P-G axis was impaired in BMAL1 -KO mice. Moreover, both BMAL1 -KO mice and BMAL1-knockdown by small interfering RNA (siRNA) in vitro cultured steroidogenic cells showed that BMAL1 was associated with gonadal steroidogenesis and expression of related genes. Importantly, BMAL1 also participates in pathogenesis of human reproductive diseases. In this review, we elaborate on the impaired reproduction of BMAL1-KO mice including the reproductive organs, reproductive endocrine hormones, and reproductive processes, highlighting the vital role of BMAL1 in fertility and reproductive endocrinology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Li, Xu, Ying, Qu, Jiang, Zhang, Yue, Zhou, Ruan, Li and Mu.)

The H5N1 subtype of the avian influenza virus causes sporadic but fatal infections in humans. H5N1 virus infection leads to the disruption of the alveolar epithelial barrier, a pathologic change that often progresses into acute respiratory distress syndrome (ARDS) and pneumonia. The mechanisms underlying this remain poorly understood. Here we report that H5N1 viruses downregulate the expression of intercellular junction proteins (E-cadherin, occludin, claudin-1, and ZO-1) in several cell lines and the lungs of H5N1 virus-infected mice. H5N1 virus infection activates TGF-β-activated kinase 1 (TAK1), which then activates p38 and ERK to induce E3 ubiquitin ligase Itch expression and to promote occludin ubiquitination and degradation. Inhibition of the TAK1-Itch pathway restores the intercellular junction structure and function in vitro and in the lungs of H5N1 virus-infected mice. Our study suggests that H5N1 virus infection impairs the alveolar epithelial barrier by downregulating the expression of intercellular junction proteins at the posttranslational level., (© 2022. The Author(s).)

Purpose: To compare the anatomical and functional outcomes of macular hole retinal detachment (MHRD) in high myopia after pars plana vitrectomy (PPV) with face-down positioning and adjustable positioning., Methods: Fifty-three eyes from 53 patients with MHRD were analyzed in this study. All patients received PPV with silicon oil for tamponade and then subdivided into 2 groups: 28 were included in a face-down positioning group and 25 were included in the adjustable positioning group. Patients were followed up for at least 6 months. The main outcome was the rate of anatomical macular hole (MH) closure and retinal reattachment. Secondary outcome measures were the best-corrected visual acuity and postoperative complications., Results: There was no significant difference in the rate of MH closure (53.6 vs. 72.0%, p = 0.167) and retinal reattachment (100 vs. 96%, p = 0.472) between the face-down group and adjustable group. Compared with the mean preoperative best-corrected visual acuity (BCVA), the mean postoperative BCVA at the 6-month follow-up improved significantly in both groups ( p = 0, both). But there was no significant difference in the mean postoperative BCVA ( p = 0.102) and mean BCVA improvement ( p = 0.554) at 6 months after surgery between the two groups. There was no significant difference in the high intraocular pressure (IOP) after surgery between the two groups (53.6 vs. 44%, p = 0.487). There were no other complications that occurred during the follow-up., Conclusion: Adjustable positioning after PPV with silicon oil tamponade for MHRD repair is effective and safe. Face-down positioning does not seem to be necessary for all patients with MHRD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gao, Ruan, Chen, Yu, Xing, Du, Qi and Li.)

Humans have been suffering from vitiligo for a long time. Target vitiligo drugs have yet been approved. Activation of Wnt/β-catenin signalling has potential in the therapeutic use of vitiligo, so exploring new drugs that specifically directly activate Wnt is worthwhile to obtain new anti-vitiligo agents. In this work, two portions design and synthesis were put into effect. firstly, 17 phenanthridine derivatives with C-4 substitutes were designed and synthesized, which compounds 4, 6, 12, 13 served as H-acceptor with protein showed enhance melanogenesis activity; Secondly, 7 hybrid new scaffolds of compounds were designed and synthesized, scaffold hopping compound 36 that aromatic benzene was replaced pyrazole on ring C showed enhance melanogenesis and tyrosinase activity; The last and most important, a comprehensive optimization and SARs of compound 36 were carried out, compounds 41 and 43 shared phenolic hydroxyl or 3-methyl-pyridine substitutes at C-7 position remarkably improved the capacity of melanogenesis and tyrosinase activity. Compound 43 were identified as new anti-vitiligo agents that specifically activate the Wnt/β-catenin signalling pathway by targeting Axin. Structure-activity relationship analysis implied that H-acceptor substitutions at the C-4 position and phenolic hydroxyl or pyridine substitutions at the C-7 position would improve the activities of the compounds. These findings reveal a new therapeutic strategy for vitiligo, and compounds 41 and 43 may represent potential compounds for vitiligo treatment., (Copyright © 2021. Published by Elsevier Inc.)

Online social networks (OSNs) have become a powerful tool to study collective human responses to extreme events such as earthquakes. Most previous research concentrated on a single platform and utilized users' behaviors on a single platform to study people's general responses. In this study, we explore the characteristics of people's behaviors on different OSNs and conduct a cross-platform analysis of public responses to earthquakes. Our findings support the Uses and Gratification theory that users on Reddit and Twitter are engaging with platforms that they may feel best reflect their sense of self. Using the 2019 Ridgecrest earthquakes as our study cases, we collected 510,579 tweets and 45,770 Reddit posts (including 1437 submissions and 44,333 comments) to answer the following research questions: (1) What were the similarities and differences between public responses on Twitter and Reddit? (2) Considering the different mechanisms of Twitter and Reddit, what unique information of public responses can we learn from Reddit as compared with Twitter? By answering these research questions, we aim to bridge the gap of cross-platform public responses research towards natural hazards. Our study evinces that the users on the two different platforms have both different topics of interest and different sentiments towards the same earthquake, which indicates the necessity of investigating cross-platform OSNs to reveal a more comprehensive picture of people's general public responses towards certain disasters. Our analysis also finds that r/conspiracy subreddit is one of the major venues where people discuss the 2019 Ridgecrest earthquakes on Reddit and different misinformation/conspiracies spread on Twitter and Reddit platforms (e.g., "Big one is coming" on Twitter and "Nuclear test" on Reddit)., (© 2022. The Author(s).)

(1) Background: Endometrial cancer is the most prevalent cause of gynecological malignant tumor worldwide. The prognosis of endometrial carcinoma patients with distant metastasis is poor. (2) Method: The RNA-Seq expression profile and corresponding clinical data were downloaded from the Cancer Genome Atlas database and the Gene Expression Omnibus databases. To predict patients' overall survival, a 9 EMT-related genes prognosis risk model was built by machine learning algorithm and multivariate Cox regression. Expressions of nine genes were verified by RT-qPCR. Responses to immune checkpoint blockades therapy and drug sensitivity were separately evaluated in different group of patients with the risk model. (3) Endometrial carcinoma patients were assigned to the high- and low-risk groups according to the signature, and poorer overall survival and disease-free survival were showed in the high-risk group. This EMT-related gene signature was also significantly correlated with tumor purity and immune cell infiltration. In addition, eight chemical compounds, which may benefit the high-risk group, were screened out. (4) Conclusions: We identified a novel EMT-related gene signature for predicting the prognosis of EC patients. Our findings provide potential therapeutic targets and compounds for personalized treatment. This may facilitate decision making during endometrial carcinoma treatment.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unprecedented in human history. As a major structural protein, nucleocapsid protein (NPro) is critical to the replication of SARS-CoV-2. In this work, 17 NPro-targeting phenanthridine derivatives were rationally designed and synthesized, based on the crystal structure of NPro. Most of these compounds can interact with SARS-CoV-2 NPro tightly and inhibit the replication of SARS-CoV-2 in vitro. Compounds 12 and 16 exhibited the most potent anti-viral activities with 50% effective concentration values of 3.69 and 2.18 μM, respectively. Furthermore, site-directed mutagenesis of NPro and Surface Plasmon Resonance (SPR) assays revealed that 12 and 16 target N-terminal domain (NTD) of NPro by binding to Tyr109. This work found two potent anti-SARS-CoV-2 bioactive compounds and also indicated that SARS-CoV-2 NPro-NTD can be a target for new anti-virus agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Among the various histologic subtypes of ovarian cancers (OCs), ovarian clear cell carcinoma (OCCC) represents a great challenge due to its disease aggressiveness and resistance to chemotherapy. IGF1 is overexpressed in epithelial ovarian cancer (EOC), and IGF1 pathway activation is related to the chemoresistance of various cancers. In this study, we found that the expression level of IGF1 was higher in OCCC than in the most common type of OC, high-grade serous adenocarcinoma (HGSC). Then, we investigated the role of IGF1 pathway activation in the progression of OCCC, observing that activation of the IGF1 pathway using IGF1 promoted the proliferation and migration of ES2 cells, while inactivation of the IGF1 pathway using the selective IGF1R inhibitor OSI-906 reversed the alteration mediated by IGF1. Based on the role of the IGF1 pathway in cancer chemoresistance, we proposed that OSI-906 may restore the sensitivity of OCCC to cisplatin. We first validated that IGF1 increased the IC50 value of cisplatin in ES2 cells, while OSI-906 decreased it. Then we confirmed that IGF1 decreased the apoptosis rate of ES2 cells induced by cisplatin, while OSI-906 increased it. Finally, we conducted animal experiments to investigate whether OSI-906 helps cisplatin control the growth of OCCC. As expected, OSI-906 increased the effect of cisplatin in attenuating the growth of OCCC in vivo. Therefore, we conclude that using OSI-906 may be an effective method to restore the sensitivity of OCCC to cisplatin by targeting the IGF1R/AKT pathway., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

A new dust data assimilation scheme has been developed for the UK version of the Laboratoire de Météorologie Dynamique Martian General Circulation Model. The Analysis Correction scheme (adapted from the UK Met Office) is applied with active dust lifting and transport to analyze measurements of temperature, and both column-integrated dust optical depth (CIDO), τ ref (rescaled to a reference level), and layer-integrated dust opacity (LIDO). The results are shown to converge to the assimilated observations, but assimilating either of the dust observation types separately does not produce the best analysis. The most effective dust assimilation is found to require both CIDO (from Mars Odyssey/THEMIS) and LIDO observations, especially for Mars Climate Sounder data that does not access levels close to the surface. The resulting full reanalysis improves the agreement with both in-sample assimilated CIDO and LIDO data and independent observations from outside the assimilated data set. It is thus able to capture previously elusive details of the dust vertical distribution, including elevated detached dust layers that have not been captured in previous reanalyzes. Verification of this reanalysis has been carried out under both clear and dusty atmospheric conditions during Mars Years 28 and 29, using both in-sample and out of sample observations from orbital remote sensing and contemporaneous surface measurements of dust opacity from the Spirit and Opportunity landers. The reanalysis was also compared with a recent version of the Mars Climate Database (MCD v5), demonstrating generally good agreement though with some systematic differences in both time mean fields and day-to-day variability., (© 2021 The Authors.)

Background: We estimated the global burden of ovarian cancer (OC) in 194 countries and territories between 2007 and 2017., Methods: Data were extracted from the Global Burden of Disease (GBD), Injuries, and Risk Factors 2017 study., Results: Globally, 286 126.80 (95% UI = 278 075.38-295 311.41) incident cases, 4.67 million (4.53-4.83) disability-adjusted life-years (DALYs), and 175 981.99 (171 384.15-181 198.43) deaths were reported in 2017. The age-standardized incidence and DALY rates increased by 2.05% and 1.34% during 2007-2017, respectively, while the age-standardized mortality rate decreased by -0.14%. The age-standardized incidence, DALY, and mortality rates in 2017 were the highest in the high socio-demographic index (SDI) quintile, but the largest percentage increase during 2007-2017 was in the low-SDI quintile. Among regions, Central Europe showed the highest 2017 age-standardized incidence, DALY, and mortality rates, whereas South Asia and East Asia showed the largest percentage increases in both rates during 2007-2017. Among countries, India showed the largest percentage increase in age-standardized incidence and DALY rates, whereas Iran showed the largest percentage increase in age-standardized mortality rates. Globally, the largest percentage increase in risk-attributable DALYs was associated with metabolic risk factors (e.g., high fasting plasma glucose levels)., Conclusion: The global age-standardized incidence, DALYs, and mortality rates of OC remain stable during 2007-2017. However, the low SDI quintile and the greatest burden in South and East Asia, India, and Iran suggested that more targeted strategies should be performed in those regions and countries., (© 2021 Japan Society of Obstetrics and Gynecology.)