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Objective To investigate the safety of different time decompression in patients undergoing coronary intervention via distal radial artery. Methods From December 2022 to December 2023, a total of 139 patients undergoing coronary intervention through distal radial artery in the department of cardiovascular medicine of the First Affiliated Hospital of Nanjing Medical University were selected and divided into three groups by the random number table method. Group A, 47 cases, underwent first decompression 30 minutes after operation. Group B, 47 cases, underwent initial decompression 1 h after operation. Group C, 45 cases, underwent initial decompression 2 h after operation. Postoperative limb pain score, comfort score and palm-diameter swelling rate immediately after operation, 30 min, 1 h, 2 h and 4 h, and postoperative puncture bleeding were compared among the three groups. Results Immediately after operation, the pain score, comfort score and the swelling rate of the circumference of the palm among the three groups showed no statistical significance (P > 0.05) . The limb pain score of group A at 30 min, 1 h, 2 h and 4 h after operation was lower than that in group B and group C (P < 0.05), and the comfort score was higher than that in group B and group C (P < 0.05) . The swelling rate of the palms of group A at 1 h, 2 h and 4 h after operation was lower than that in group B and group C (P < 0.05) . There was no significant difference in postoperative bleeding among the three groups (P > 0.05) . Conclusion The first decompression within 30 minutes after operation is safe and effective for patients undergoing coronary intervention through distal radial artery, which can significantly relieve pain, swelling discomfort and improve comfort, and is worthy of promotion in clinical work.

Abstract Objective Some correlations between thyroid disorders and insomnia have been found in previous studies; however, the causal relationship between them is unclear. The aim of this study was to investigate the causal relationship between insomnia and five thyroid disorders (hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer). Methods We assessed the causal relationship between insomnia and thyroid disorders using inverse variance weighted, weighted median, and Mendelian randomization (MR)‐Egger analyses in MR analyses and then used inverse MR analyses to assess the causal relationship between thyroid disorders and insomnia. Results MR analysis showed that insomnia did not increase the risk of hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer. However, reverse MR analysis showed that thyroid cancer increased the risk of insomnia (OR = 1.01, 95%CI: 1.00–1.02, p = .01), and the other four thyroid disorders had no direct causal relationship with insomnia. Sensitivity analyses indicated that the results were robust and no pleiotropy or heterogeneity was detected. Conclusion This study did not find evidence of a bidirectional causal relationship between genetically predicted insomnia and hyperthyroidism, hypothyroidism, thyroiditis, and thyroid nodules. However, we found that although insomnia does not increase the risk of thyroid cancer, thyroid cancer does increase the risk of insomnia.

ObjectiveTo investigate diagnostic approaches for preoperative localization of secondary hyperparathyroidism, as well as to give surgeons with precise parathyroid gland localization and imaging so that surgery can be performed safely.MethodsThe clinical data of 710 patients with secondary hyperparathyroidism who underwent surgery in our center from October 2009 to October 2023 were retrospectively analyzed. The changes in calcium, phosphorus, and parathyroid hormone levels were observed to ascertain the anatomical location and number of parathyroid glands.ResultsAmong the 710 patients, 55 underwent total parathyroidectomy, the others underwent total parathyroidectomy with autotransplantation. In total, 2,658 parathyroid glands were removed, with 43 glands being removed in 35 reoperation cases. The median parathyroid hormone level at 6 months postoperatively was 13.40 (interquartile range, 7.00-29.80) pg/mL. The detection rates of the parathyroid glands before first and repeat surgeries were higher using 99mTc-MIBI SPECT/CT fusion imaging than ultrasound (P

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Abstract Objective It has been observed that the prognosis of patients with HER2‐positive metastatic breast cancer has improved significantly with HER2‐targeted agents. However, there is still a lack of evidence regarding first‐line anti‐HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti‐HER2 treatment in these patients. Methods Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer were enrolled. Pyrotinib plus albumin‐bound paclitaxel were used as first‐line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. Results From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow‐up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand‐foot syndrome (3.7%). Toll‐like receptor 3 (TLR3) and Proto‐oncogene tyrosine‐protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. Conclusions This study demonstrates that pyrotinib plus albumin‐bound paclitaxel as a first‐line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

Background: Cisplatin (DDP) is the principal agent used for chemotherapy in patients with non-small cell lung cancer (NSCLC). Nevertheless, DDP resistance is an essential cause for a worse prognosis of patient. Therefore, this study proposes to discover features of miR-424-5p in DDP resistance of NSCLC. Method: After exogenous modulation of miR-424-5p expression, A549 cell activity was measured using CCK-8 and flow cytometry. A549/DDP and A549/DDP-associated subcutaneous tumor model were constructed to investigate the effect of miR-424-5p on DDP resistance in NSCLC in vivo. TargetScan and JASPAR databases predicted the potential molecular mechanism of miR-424-5p. A549-and A549/DDP-derived exosomes were isolated and characterized using a transmission electron microscope and nanoparticle tracking analysis. Result: Overexpression of miR-424-5p facilitated proliferation and DDP resistance in A549 cells, and knockdown of miR-424-5p did the opposite. Knockdown of miR-424-5p enhanced DDP restriction on tumor weight and volume. Moreover, SOCS5 and SOCS56 (SOCS5/6) were downstream targets of miR-424-5p. miR-424-5p down-regulated SOCS5/6 expression to activate JAK2/STAT3 and PI3K/AKT pathways. Notably, tumor protein p53 (TP53) is a transcription factor for the miR-424-5p host gene, as confirmed by the dual-luciferase reporter gene. Cellular and animal experiments indicated that TP53 limited the regulatory function of miR-424-5p on NSCLC growth, DDP resistance, and related molecules. Interestingly, miR-424-5p was markedly enriched in A549/DDP cell-derived exosomes than in A549 cell-derived exosomes, and TP53 down-regulated miR-424-5p expression in A549/DDP cell-derived exosomes. Conclusion: DDP-resistant cell-derived exosome miR-424-5p contributes to NSCLC growth and DDP resistance by targeting SOCS5 and SOCS6 to activate JAK2/STAT3 and PI3K/AKT pathways, which are blocked by TP53.

Abstract Bionic multifunctional structural materials that are lightweight, strong, and perceptible have shown great promise in sports, medicine, and aerospace applications. However, smart monitoring devices with integrated mechanical protection and piezoelectric induction are limited. Herein, we report a strategy to grow the recyclable and healable piezoelectric Rochelle salt crystals in 3D-printed cuttlebone-inspired structures to form a new composite for reinforcement smart monitoring devices. In addition to its remarkable mechanical and piezoelectric performance, the growth mechanisms, the recyclability, the sensitivity, and repairability of the 3D-printed Rochelle salt cuttlebone composite were studied. Furthermore, the versatility of composite has been explored and applied as smart sensor armor for football players and fall alarm knee pads, focusing on incorporated mechanical reinforcement and electrical self-sensing capabilities with data collection of the magnitude and distribution of impact forces, which offers new ideas for the design of next-generation smart monitoring electronics in sports, military, aerospace, and biomedical engineering.

Background Systemic chemotherapy or chemoradiation therapy has proven to be effective in treating advanced biliary tract carcinoma (BTC). However, its efficacy in the adjuvant setting remains controversial. Therefore, this study aimed to determine the prognostic significance of genomic biomarkers in resected BTC and their potential role in stratifying patients for adjuvant treatment. Methods We retrospectively reviewed 113 BTC patients who underwent curative‐intent surgery and had available tumor sequencing data. Disease‐free survival (DFS) was the primary outcome examined and univariate analysis was used to identify gene mutations with prognostic value. Favorable and unfavoratble gene subsets were distinguished from the selected genes through grouping, respectively. Multivariate Cox regression was used to identify independent prognostic factors of DFS. Results Our results indicated that mutations in ACVR1B, AR, CTNNB1, ERBB3, and LRP2 were favorable mutations, while mutations in ARID1A, CDKN2A, FGFR2, NF1, NF2, PBRM1, PIK3CA, and TGFBR1 were unfavorable mutations. In addition to age, sex, and node positive, favorable genes (HR = 0.15, 95% CI = 0.04–0.48, p = 0.001) and unfavorable genes (HR = 2.86, 95% CI = 1.51–5.29, p = 0.001) were identified as independent prognostic factors for DFS. Out of the 113 patients, only 35 received adjuvant treatment whereas the majority (78) did not. For patients with both favorable and unfavorable mutations undetected, adjuvant treatment showed negative effect on DFS (median DFS: S441 vs. 956 days, p = 0.010), but there was no significant difference in DFS among those in other mutational subgroups. Conclusions Genomic testing might be useful in guiding the decisions regarding adjuvant treatment in BTC.

Abstract Urothelial bladder cancer (UBC) is one of the most prevalent malignancies worldwide, with striking tumor heterogeneity. Elucidating the molecular mechanisms that can be exploited for the treatment of aggressive UBC is a particularly relevant goal. Protein ubiquitination is a critical post-translational modification (PTM) that mediates the degradation of target protein via the proteasome. However, the roles of aberrant protein ubiquitination in UBC development and the underlying mechanisms by which it drives tumor progression remain unclear. In this study, taking advantage of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9 technology, we identified the ubiquitin E3 ligase ANAPC11, a critical subunit of the anaphase-promoting complex/cyclosome (APC/C), as a potential oncogenic molecule in UBC cells. Our clinical analysis showed that elevated expression of ANAPC11 was significantly correlated with high T stage, positive lymph node (LN) metastasis, and poor outcomes in UBC patients. By employing a series of in vitro experiments, we demonstrated that ANAPC11 enhanced the proliferation and invasiveness of UBC cells, while knockout of ANAPC11 inhibited the growth and LN metastasis of UBC cells in vivo. By conducting immunoprecipitation coupled with mass spectrometry, we confirmed that ANAPC11 increased the ubiquitination level of the Forkhead transcription factor FOXO3. The resulting decrease in FOXO3 protein stability led to the downregulation of the cell cycle regulator p21 and decreased expression of GULP1, a downstream effector of androgen receptor signaling. Taken together, these findings indicated that ANAPC11 plays an oncogenic role in UBC by modulating FOXO3 protein degradation. The ANAPC11–FOXO3 regulatory axis might serve as a novel therapeutic target for UBC.

ABSTRACT: Objectives: This study attempted to identify the relationship between antibiotic exposure and risk of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection. Methods: Antibiotic exposure was analysed as a risk factor for CRKP infection, cases of which were extracted from research articles indexed in PubMed, EMBASE, and the Cochrane Library. Relevant studies published until January 2023 were reviewed, and a meta-analysis was conducted on antibiotic exposure within four types of control groups, which comprised 52 studies. Results: The four types of control groups included carbapenem-susceptible K. pneumoniae infections (CSKP; comparison 1); other infections, especially without CRKP infection (comparison 2); CRKP colonisation (comparison 3); and no infection (comparison 4). Carbapenems exposure and Aminoglycosides exposure were two risk factors common to the four comparison groups. Compared with the risk of CSKP infection, tigecycline exposure in bloodstream infections and quinolone exposure within 30 days were associated with an increased risk of CRKP infection. However, the risk of CRKP infection associated with tigecycline exposure in mixed (MIX) infections (infections involving two or more different infection sites) and quinolone exposure within 90 days was similar to the risk of CSKP infection. Conclusion: Carbapenems and Aminoglycosides exposure are likely risk factors for CRKP infection. Antibiotic exposure time as a continuous variable was not associated with the risk of CRKP infection, compared with the risk of CSKP infection. Tigecycline exposure in MIX infections and quinolone exposure within 90 days may not increase the risk of CRKP infection.

BackgroundParvimonas micra (P. micra), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated with diverse diseases. The diagnostic trajectory for P. micra-related diseases encounters delays, often with severe consequences, including fatality, attributed to the absence of symptom specificity and challenges in culture. The absence of a consensus on the diagnostic and therapeutic approaches to P. micra exacerbates the complexity of addressing associated conditions. This study aims to elucidate and scrutinize the clinical manifestations linked to P. micra, drawing insights from an extensive literature review of pertinent case reports.Case presentationA 53-year-old male sought medical attention at our institution presenting with recurrent hemoptysis. Empirical treatment was initiated while awaiting pathogen culture results; however, the patient’s symptoms persisted. Subsequent metagenomic next-generation sequencing (mNGS) analysis revealed a pulmonary infection attributable to P. micra. Resolution of symptoms occurred following treatment with piperacillin sulbactam sodium and moxifloxacin hydrochloride. A comprehensive literature review, utilizing the PubMed database, was conducted to assess case reports over the last decade where P. micra was identified as the causative agent.ConclusionThe literature analysis underscores the predilection of P. micra for immunocompromised populations afflicted by cardiovascular diseases, diabetes, orthopedic conditions, and tumors. Risk factors, including oral and periodontal hygiene, smoking, and alcohol consumption, were found to be associated with P. micra infections. Clinical manifestations encompassed fever, cough, sputum production, and back pain, potentially leading to severe outcomes such as Spondylodiscitis, septic arthritis, lung abscess, bacteremia, sepsis, and mortality. While conventional bacterial culture remains the primary diagnostic tool, emerging technologies like mNGS offer alternative considerations. In terms of treatment modalities, β-lactam antibiotics and nitroimidazoles predominated, exhibiting recovery rates of 56.10% (46/82) and 23.17% (19/82), respectively. This case report and literature review collectively aim to enhance awareness among clinicians and laboratory medicine professionals regarding the intricacies of P. micra-associated infections.

ObjectiveThis study aimed to develop and apply a prediction model to estimate the probability of lateral lymph node metastasis (LLNM) in patients with cN0 unilateral papillary thyroid carcinoma (PTC) with central lymph node metastasis (CLNM).SettingAll study data were collected from a single tertiary hospital.MethodsUnivariable and multivariable logistic regression analyses were used to explore independent predictors of LLNM in the derivation and internal validation cohorts, which were used to construct and validate a nomogram. Another 96 patients were included prospectively to evaluate the efficacy of this nomogram.ResultsMaximum tumor diameter greater than 1.0 cm (OR, 2.712; 95% CI, 1.412–5.210), multifocality (OR, 2.758; 95% CI, 1.120–6.789), the number of CLNM ≥3 (OR, 2.579; 95% CI, 1.315–5.789), CLNM ratio ≥0.297 (OR, 2.905; 95% CI, 1.396–6.043), and tumors located in the upper portion (OR 2.846, 95% CI 1.151–7.039) were independent predictors associated with LLNM. The prediction model showed excellent discrimination with an AUC of 0.731 (95% CI, 0.635–0.827). Novel risk stratification for LLNM was constructed based on this nomogram. In the prospective cohort, we stratified these patients into three risk subgroups: low-, moderate-, and high-risk subgroups and we found that the probability of LLNM was positively correlated with the total points from the nomogram.ConclusionThis nomogram was applied in prospective clinical practice and distinguished PTC patients with a genuinely high risk of LLNM. Surgeons can use our nomogram to tailor the surgical plan and to credibly determine further postoperative therapy.

Abstract Background Colorectal cancer (CRC) is the third leading cause of cancer‐related deaths worldwide. Studies have shown that the DNA damage response (DDR) mutation is strongly associated with microsatellite instability (MSI) status and is an indication for patients with CRCs receiving immune checkpoint inhibitor (ICI) treatment. However, DDR mutation in microsatellite stable (MSS) CRC remains unclear. Methods In this study, Fisher's exact test, Student'st‐test, Wilcoxon rank‐sum test and Cox proportional hazards regression model were performed, and a p value of

In order to improve the clarity of the development of the markers in the digestive tract，the formulation and preparation process of high drug loading pellets of barium sulfate were explored and optimized. Firstly, extrusion-spheronization process was used to prepare the barium sulfate-loaded pellet cores with barium sulfate as a model drug. Secondly, the powder layering technique was applied to prepare the barium sulfate pellets by coating the core with barium slfate drug layer. Finally, the influencing factors of formulation and process on the properties of the pellet cores or pellets were investigated, and the process and formulation parameters were optimized by single factor test and orthogonal test based on the index of roundness, friability, and yield. The results show that the obtained barium sulfate-loaded pellet cores have possessed high roundness, the preparation method of the pellet cores is stable, the drug-loading rate is up to 80%, and the yield of 550~700 μm (mesh of 24～30) is 8533%.The content of barium sulfate in the powder of powder layering method is about 90%, and the yield of 830~1 180 μm (mesh of 14～20) is 9033%. The prepared barium sulfate pellets are white spheres with uniform particle size distribution, low friability, high density, smooth surface, and better tensile strength, which can act as intermediate products to be coated in the following step. The barium sulfate pellets prepared by this method have the characteristic of high drug-loaded and achieve the desired experimental purpose, which can provide useful information for further study and utilization of barium sulfate pellets and a new choice for the design of radioopaque markers.

Background: In patients with hepatocellular carcinoma (HCC), the tumor microenvironment (TME) is resistant to immunotherapy because of its specificity. It is meaningful to explore the role of macrophage, which is one of the most abundant immune cells in the TME, in cellular communication and its effect on the prognosis and immunotherapy of HCC.Methods: Dimensionality reduction and clustering of the single-cell RNA-seq data from the GSE149614 dataset were carried out to identify the cellular composition of HCC. CellChat was used to analyze the communication between different cells. The specifically highly expressed genes of macrophages were extracted for univariate Cox regression analysis to obtain prognostic genes for HCC cluster analysis, and the risk system of macrophage-specifically highly expressed genes was developed by random forest analysis and multivariate Cox regression analysis. Prognosis, TME infiltration, potential responses to immunotherapy, and antineoplastic drugs were compared among molecular subtypes and between risk groups.Results: We found that HCC included nine identifiable cell types, of which macrophages had the highest communication intensity with each of the other eight cell types. Of the 179 specifically highly expressed genes of macrophage, 56 were significantly correlated with the prognosis of HCC, which classified HCC into three subtypes, which were reproducible and produced different survival outcomes, TME infiltration, and immunotherapy responses among the subtypes. In the integration of four macrophage-specifically highly expressed genes for the development of a risk system, the risk score was significantly involved in higher immune cell infiltration, poor prognosis, immunotherapy response rate, and sensitivity of six drugs.Conclusion: In this study, through single-cell RNA-seq data, we identified nine cell types, among which macrophage had the highest communication intensity with the rest of the cell types. Based on specifically highly expressed genes of macrophage, we successfully divided HCC patients into three clusters with distinct prognosis, TME, and therapeutic response. Additionally, a risk system was constructed, which provided a potential reference index for the prognostic target and preclinical individualized treatment of HCC.

Secondary Hyperparathyroidism (SHPT) is a common complication of end-stage renal disease (ESRD), and parathyroid surgery (PTX) is an effective way to treat patients with severe SHPT. ESRD has multiple associations with cerebrovascular diseases. For example, the incidence of stroke in patients with ESRD is 10 times higher than that in the general population, the risk of death after acute stroke is three times higher, and the risk of hemorrhagic stroke is significantly higher. High/low serum calcium, high PTH, low serum sodium, high white blood cell count, previous occurrences of cerebrovascular events, polycystic kidney disease (as a primary disease), and the use of anticoagulants are independent risk factors for hemorrhagic stroke in hemodialysis patients with uremia. The risk of stroke in patients who undergo PTX decreases significantly in the second year of follow-up and persist thereafter. However, studies on the risk of perioperative stroke in SHPT patients are limited. After undergoing PTX, the PTH levels in SHPT patients drop suddenly, they undergo physiological changes, bone mineralization increases, and calcium in the blood gets redistributed, often accompanied by severe hypocalcemia. Serum calcium might influence the occurrence and development of hemorrhagic stroke at various stages. To prevent bleeding from the operated area, the use of anticoagulants after surgery is reduced in some cases, which often decreases the frequency of dialysis and increases the quantity of fluid in the body. An increase in the variation in blood pressure, instability of cerebral perfusion, and extensive intracranial calcification during dialysis promote hemorrhagic stroke, but these clinical problems have not received enough attention. In this study, we reported the death of an SHPT patient who suffered a perioperative intracerebral hemorrhage. Based on this case, we discussed the high-risk factors for perioperative hemorrhagic stroke in patients who undergo PTX. Our findings might help in the identification and early prevention of the risk of profuse bleeding in patients and provide reference for the safe performance of such operations.

Abstract Existing bone tissue engineering strategies aim to achieve minimize surgical trauma, stabilize the injured area, and establish a dynamic osteogenic microenvironment. The cutting‐edge bone glue developed in this study satisfies these criteria. Inspired by the excellent adhesive properties of mussels, herein, a super osteogenic glue (L‐DPZ) that integrates poly(vinyl alcohol), L‐dopa amino acid, and zeolitic imidazolate framework‐8 characterized by catechol–metal coordination is used to successfully adhere to hard tissue with a maximum adhesive strength of 10 MPa, which is much higher than those of commercial and previously reported bone glues. The stable hard tissue adhesion also enables it to adhere strongly to luxated or broken teeth, Bio‐Oss (a typical bone graft material), and splice fragments from comminuted fractures of the rabbit femur. Then, it is testified that the L‐DPZ hydrogels exhibit satisfactory biocompatibility, stable degradability, and osteogenic ability in vitro. Moreover, the ability to anchor Bio‐Oss and sustained osteogenesis of L‐DPZ result in satisfactory healing in calvarial bone defect models in rabbits, as observed by increased bone thickness and the ingrowth of new bone tissue. These results are expected to demonstrate solutions to clinical dilemmas such as comminuted bone fracture fixation, bone defect reconstruction, and teeth dislocation replantation.

Abstract Objective To compare the surgical outcomes between the transoral-vestibular robotic thyroidectomy (TOVRT) and bilateral axillo-breast approach robotic thyroidectomy (BABART). Methods A total of 99 patients with papillary thyroid carcinoma but no distant metastasis were enrolled in this study from May 2020 to April 2021. Lobectomy or total thyroidectomy with central lymph node dissection were performed in all cases. All 99 patients were received an ultrasound guided fine needle aspiration biopsy prior to surgical intervention, out of which 49 patients underwent TOVRT, while rest 50 patients underwent BABART. During the procedure, intraoperative neuromonitoring system was used and all recurrent laryngeal nerves (RLNs) were preserved, additionally for TOVRT procedure, three intraoral ports or right axillary fold incision was used to allow for fine countertraction of tissue for radical oncological dissection. The clinical data including age, gender, height, weight, BMI, primary tumor size, number of central lymph node removed, central lymph node metastasis, operating time, total hospital stays, postoperative hospital stays, total postoperative drainage volume, postoperative pain score, cosmetic effect and complications were recorded and analyzed. Results There were no significant differences in gender, height, weight, BMI and removed central lymph nodes between the two groups (P > 0.05). Patients accepted TOVRT were younger and had smaller primary tumor size than those who accepted BABART. The TOVRT group had a longer surgical time than the BABART group, but with smaller postoperative drainage volume and superior cosmetic effect (under visual analogue scale, VAS) (P 0.05). Last but not least, certain peculiar complications were observed in TOVRT group: paresthesia of the lower lip and the chin (one case), surgical site infection (one case) and skin burn (one case). Conclusion Transoral-vestibular robotic thyroidectomy is safe and feasible for certain patients, which could be considered an alternative approach for patients who require no scarring on their neck.

Centipedegrass (Eremochloa ophiuroides (Munro.) Hack.) is a species originating in China and is an excellent warm-season turfgrass. As a native species in southern China, it is naturally distributed in the phosphorus-deficient and aluminum-toxic acid soil areas. It is important to research the molecular mechanism of centipedegrass responses to phosphorus-deficiency and/or aluminum-toxicity stress. Quantitative Real-Time PCR (qRT-PCR) is a common method for gene expression analysis, and the accuracy of qRT-PCR results depends heavily on the stability of internal reference genes. However, there are still no reported stable and effective reference genes for qRT-PCR analysis of target genes under the acid-soil-related stresses in different organs of centipedegrass. For scientific rigor, the gene used as a reference for any plant species and/or any stress conditions should be first systematically screened and evaluated. This study is the first to provide a group of reliable reference genes to quantify the expression levels of functional genes of Eremochloa ophiuroides under multiple stresses of P deficiency and/or aluminum toxicity. In this study, centipedegrass seedlings of the acid-soil-resistant strain ‘E041’ and acid-soil-sensitive strain ‘E089’ were used for qRT-PCR analysis. A total of 11 candidate reference genes (ACT, TUB, GAPDH, TIP41, CACS, HNR, EP, EF1α, EIF4α, PP2A and actin) were detected by qRT-PCR technology, and the stability of candidate genes was evaluated with the combination of four internal stability analysis software programs. The candidate reference genes exhibited differential stability of expression in roots, stems and leaves under phosphorus-deficiency and/or aluminum-toxicity stress. On the whole, the results showed that GAPDH, TIP41 and HNR were the most stable in the total of samples. In addition, for different tissues under various stresses, the selected reference genes were also different. CACS and PP2A were identified as two stable reference genes in roots through all three stress treatments (phosphate deficiency, aluminum toxicity, and the multiple stress treatment of aluminum toxicity and phosphate deficiency). Moreover, CACS was also stable as a reference gene in roots under each treatment (phosphate deficiency, aluminum toxicity, or multiple stresses of aluminum toxicity and phosphate deficiency). In stems under all three stress treatments, GAPDH and EIF4α were the most stable reference genes; for leaves, PP2A and TIP41 showed the two highest rankings in all three stress treatments. Finally, qRT-PCR analysis of the expression patterns of the target gene ALMT1 was performed to verify the selected reference genes. The application of the reference genes identified as internal controls for qRT-PCR analysis will enable accurate analysis of the target gene expression levels and expression patterns in centipedegrass under acid-soil-related stresses.

Background. Sepsis mortality and morbidity are aggravated by acute lung injury (ALI) or acute respiratory distress syndrome. Published studies have discovered that hyperoside (HYP) has an anti-inflammatory and therapeutic effect in many diseases. However, whether HYP treatment can attenuate sepsis-induced ALI is still obscure. Methods. In this study, a cecal ligation and puncture (CLP)-induced sepsis mouse model was constructed. The mouse lungs were harvested and assessed using proteomics, immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assay for pro-inflammatory cytokines. Human lung microvascular endothelial cells (HLMVECs) were induced with lipopolysaccharide (LPS) for the in vitro model. Results. The results showed that HYP treatment attenuated sepsis-induced ALI through an increased survival rate, decreased inflammatory factor expression, and lung tissue apoptosis. At the same time, HYP pretreatment restored angiogenesis in CLP-induced mouse lung tissues. Proteomics detection showed that Atg13 played a vital role in HYP-mediated protection against sepsis-induced ALI. The in vitro experiment showed HYP treatment attenuated LPS-induced HLMVEC damage by regulating Atg13-mediated autophagy. Inhibiting autophagy or silencing Atg13 reversed the protective effect of HYP against sepsis-induced ALI. Conclusion. Taken together, we conclude that HYP attenuated sepsis-induced ALI by regulating autophagy and inhibiting inflammation.

Brittleness is an important parameter to evaluate the performance of rock engineering. A scientific and reasonable brittleness evaluation method is of great significance to theoretical research and the engineering practice of rock mechanics. In view of the existing statistical constitutive models of rock based on the Weibull distribution being able to express various constitutive behaviors well, such as brittleness, plasticity, strain softening, this paper wants to determine rock brittleness from constitutive models. First, the parameter m, which can effectively reflect the overall characteristics of the rock stress-strain curve, and the parameter δ, which can reflect the post-peak characteristics, are selected. Then, a brittle evaluation method based on rock statistical damage constitutive parameters is proposed, and the brittleness index Bm (Bm = m·δ) is established. The feasibility is verified by the testing data of granite, sandstone and marble under different conditions. The results show that the brittleness of those hard rocks decrease with the increasing of confining pressure. For confining pressures of 5 MPa and 15 MPa, the brittleness of granite under triaxial unloading test is greater than that under triaxial compression test. The calculation results quantitatively reflect the brittle characteristics of sandstone, marble and granite in the test. Compared with the existing representative brittleness indexes, it is found that the brittleness index Bm can effectively reflect the characteristics of rock brittleness decreasing with increasing confining pressure and enhancement under unloading stress path. This paper provides a way to evaluate rock brittleness from the perspective of a constitutive model, which is helpful to enrich our understanding of rock brittleness.

The shield machine tunnelling along the curve section causes more disturbance to the surrounding environment than the straight section. Pile foundation is the most commonly used foundation form in high-rise buildings, and high-rise buildings have extremely high requirements for controlling non-uniform deformation. Therefore, it is necessary to study the surface settlement and the deformation law of pile foundations caused by shield machine tunnelling along the curve section. Considering the shield machine tunnelling factors along the curve section and the coupling effect of piles and soil, the analytical calculation formula of the ground settlement and the pile foundation deformation caused by the shield machine tunnelling along the curve section is deduced. According to the actual project situation, a finite difference model (FDM) is constructed, and the correctness of the FDM and analytical prediction formula is verified by comparing the on-site monitoring data. The research shows that the error among the FDM results, the analytical prediction results, and the on-site monitoring data are small, and the surface settlement and pile foundation deformation meet the construction control standards. The friction resistance of the shield shell, the integrative gap at the shield tail (IGST), and the over-cutting gap (OG) are the main factors leading to the surface settlement. However, the shield shell friction and OG are the main reasons leading to the inner settlement of the curve section being more prominent than the outer side. The difference in the pile foundation settlement on both sides of the curve section is slight, the maximum settlement difference rate is 1.8%, and the maximum horizontal deformation rate of the pile foundation on the inner and outer sides is 9.2%, which shows that the horizontal deformation of the pile foundation is more sensitive to the asymmetrically distributed construction factors.

Developmental dyscalculia (DD) is characterized by insufficient mathematical learning ability and weaker mathematical performance than peers who are developmentally typical. As a subtype of learning disability, developmental dyscalculia contributes to deep cognitive processing deficits, mainly manifested as a lack of numerical processing ability. This study utilized event-related potentials (ERPs) technology to examine the negative priming effects (NP) between children with and without DD. Behaviorally, trends in mean reaction time (RT) were consistent between children with and without DD under prime and control conditions. The developmental dyscalculia group and the typical developmental (TD) children group showed a significant negative priming effect. However, the magnitude of the NP was significantly different between two groups, with the magnitude being significantly higher in the TD group than the DD group. In terms of the ERPs results, there were significantly larger amplitudes of P100, P200, and P300 in the TD group than that of children with DD. At the same time, in the DD group, N100 and P300 latency were significantly delayed in some electrodes than the TD group. The results indicated that there were characteristic inhibition deficits in children with DD. Inhibition defects in children with DD might be the underlying cause of the development of digital processing ability of children with DD.

In this study, we examined the effects of parental phubbing on learning burnout in elementary and secondary school students and its mechanism of action. A questionnaire method was applied to investigate parental phubbing, parent–child attachment, ego depletion, and learning burnout among 2090 elementary and secondary school students in Anhui Province, China. The results are as follows: (1) Parental phubbing was significantly correlated with parent–child attachment, ego depletion, and learning burnout; (2) Parental phubbing has an indirect impact on learning burnout in elementary and secondary school students through three pathways: a separate mediating effect on parent–child attachment, a separate mediating effect on ego depletion, and a chain mediating effect on both. Parental phubbing is a risk factor for Learning Burnout, which can positively affect Learning Burnout in elementary and secondary school students. The findings of the study contribute to revealing the influence mechanism of parental phubbing on learning burnout in elementary and secondary school students.

Slope cutting is becoming more common in engineering construction to obtain a large floor area. Slope cutting disrupts a slope’s inherent stability, causing instability and sliding. To solve the problem of geological disasters caused by artificial slope cutting, Cangxi County is used as an example to analyze the cutting slope and the height of different slope structures in the county, to study the disaster mode and disaster factors caused by slope cutting, and to analyze the influence of slope cutting height and slope cutting gradient on the disaster process. This study demonstrates that the stability of cutting on different types of slopes is weakened to different degrees, with mixed rocky-soil slopes having the strongest resistance to weakening, thick-soil slopes the second strongest, and thin-soil slopes the weakest. Slope cutting is the main factor of disaster, and rainwater infiltration promotes landslide formation. Numerical simulation is employed to determine the proximities of the slope cutting height and slope cutting gradient, and 75% of the critical value is taken as the proposed threshold value of slope cutting. The recommended cut slope threshold value corresponds to the real stable cut slope gradient on site, and the research findings can be used to guide engineering cut slope decisions in Cangxi County and other red-layer areas.

Glomerulonephritis is a key factor in leading to end-stage renal disease. Mesangial cell proliferation and macrophage infiltration are two prominent features linked in a vicious circle mechanism for glomerulonephritis progression. Herein, a novel biomimetic pH-sensitive nanomicelle (MM/HA-DXM) was constructed to synergize hyaluronic acid (HA)-activated macrophage phenotypic remodeling and dexamethasone (DXM)-mediated mesangial cell killing for precise treatment of glomerulonephritis. Owing to the camouflaged coating with endogenous macrophage membrane (MM), MM/HA-DXM could escape from RES phagocytosis and then be recruited to inflammatory glomerulus by active homing effect. Afterwards, HA-DXM nanomicelles ruptured in response to the weakly acidic glomerulonephritis microenvironment, to locally release HA and DXM. On the one hand, DXM can inhibit the abnormal proliferation of mesangial cells. On the other hand, HA transformed pro-inflammatory M1 macrophages into anti-inflammatory M2 phenotype to improve the glomerular inflammatory microenvironment. In doxorubicin-induced glomerulonephritis models, results revealed that MM/HA-DXM could specifically “homing” to inflammatory renal tissue with 4.33-fold improvement in targeting performance. In addition, in vivo pharmacodynamic results proved that after treatment with MM/HA-DXM, the proteinuria level decreased to 2.33 times, as compared with that of control group, demonstrating a superior therapeutic effect on glomerulonephritis via this collaborative two-pronged anti-inflammatory therapy strategy.

Non-small cell lung cancer (NSCLC) patients harboring MET exon 14 skipping or high MET amplification display a high rate of response to MET inhibitors. However, MET fusions in NSCLC have rarely been revealed. In this report, a 63-year-old woman with lung adenocarcinoma (LADC), harboring EGFR exon 18 G719D and exon 21 L861Q mutations, received first-generation, EGFR-tyrosine kinase inhibitor (TKI) icotinib therapy. Next generation sequencing (NGS) results only displayed an EGFR T790M point mutation following icotinib resistance. Thus, the patient was treated with osimertinib and achieved a stable disease (SD). However, disease progressed after 15 months and a novel MET fusion (CUX1 exon14-MET exon15) in addition to EGFR G719D/L861Q mutations were simultaneously detected in a tissue biopsy sample. After more than nine months, the patient subsequently achieved a PR with the combination of icotinib and crizotinib. To our knowledge, this is the first case of LADC patient displaying the presence of EGFR double uncommon mutations and an acquired novel CUX1-MET fusion that has benefited from icotinib plus crizotinib treatment. Following nine months of PR with icotinib plus crizotinib, the patient, until the time of publication, is exhibiting stable disease. The results suggest that the CUX1-MET fusion may be sensitive to crizotinib, although previous reports indicated that some MET fusion cases did not respond to crizotinib. Given this disparity, distinguishing MET fusion partners when crizotinib is used in LADC treatment is also very important.

Ambient PM2.5 was reported to be related to numerous negative health outcomes, leading to adverse public health impacts in many countries such as China. Despite the apparent reduction in PM2.5 levels over China due to its emission control policies in recent years, the health burdens were not reduced as much as expected. This calls for a comprehensive analysis to explain the reasons behind to provide a useful reference for formulating effective emission control strategies. Taking central China as an example due to its large population and high levels of PM2.5, this study quantified the spatiotemporal dynamics of premature mortality associated with PM2.5 pollution in central China for each year during 2003–2018 and applied a decomposition analysis to dissect the contribution of various driving factors including ambient PM2.5 level, demographic distribution and baseline incidence rate of four diseases related to air pollution. Results show significant spatiotemporal variations in PM2.5-attributed health impact in central China, including Henan, Hubei, and Hunan provinces. Five Henan cities had the largest PM2.5-attributable premature mortality (∼8–12 K premature mortalities), while three Hubei cities and one Hebei city had the least chronic PM2.5-related all-cause mortality numbers (

Circular RNAs (circRNAs) are broad and diverse endogenous non-coding RNAs. Emerging evidence has revealed that circRNAs play pivotal roles in cancers, regulating the gene expression by acting as a microRNA (miRNA) sponge. However, the biological functions of circRNAs in bladder cancer (BCa) remain largely unknown. In this study, we identified an altered circRNA, termed circFUT8, by screening RNA sequencing data generated from three BCa tissues and matched adjacent normal bladder tissues. Quantitative real-time PCR analysis demonstrated that circFUT8 was downregulated in BCa tissues and correlated with patients’ prognosis, histological grade, and lymph node (LN) metastasis. Functionally, gain- and loss-of-function assays indicated that circFUT8 inhibited the migration and invasion of BCa cell lines in vitro and LN metastasis in vivo. Mechanistically, circFUT8 directly bound to miR-570-3p and partially abrogated its oncogenic role, and miR-570-3p could suppress the expression of tumor suppressor gene Krüpple-like factor 10 (KLF10) by binding its 3′ untranslated region (3′ UTR). Moreover, we found that circFUT8 promoted the expression of KLF10 by competitively sponging miR-570-3p. In conclusion, circFUT8 functions as a tumor suppressor in BCa cells by targeting the miR-570-3p/KLF10 axis and may serve as a potential biomarker and therapeutic target for the management of BCa patients with LN metastasis. Keywords: circFUT8, bladder cancer, lymph node metastasis, miR-570-3p, KLF10, Slug

Flame-retardant and thermal management structures have attracted great attention due to the requirement of high-temperature exposure in industrial, aerospace, and thermal power fields, but the development of protective fire-retardant structures with complex shapes to fit arbitrary surfaces is still challenging. Herein, we reported a rotation-blade casting-assisted 3D printing process to fabricate nacre-inspired structures with exceptional mechanical and flame-retardant properties, and the related fundamental mechanisms are studied. 3-(Trimethoxysilyl)propyl methacrylate (TMSPMA) modified boron nitride nanoplatelets (BNs) were aligned by rotation-blade casting during the 3D printing process to build the “brick and mortar” architecture. The 3D printed structures are more lightweight, while having higher fracture toughness than the natural nacre, which is attributed to the crack deflection, aligned BN (a-BNs) bridging, and pull-outs reinforced structures by the covalent bonding between TMSPMA grafted a-BNs and polymer matrix. Thermal conductivity is enhanced by 25.5 times compared with pure polymer and 5.8 times of anisotropy due to the interconnection of a-BNs. 3D printed heat-exchange structures with vertically aligned BNs in complex shapes were demonstrated for efficient thermal control of high-power light-emitting diodes. 3D printed helmet and armor with a-BNs show exceptional mechanical and fire-retardant properties, demonstrating integrated mechanical and thermal protection.

Habitat reduction and increased fragmentation are urgent issues for the survival and recovery of the giant panda (Ailuropoda melanoleuca). However, changes in the distribution and microhabitat selection of giant panda habitats in different seasons in the same region have rarely been assessed. To further understand giant panda habitat requirements, this study analyzed the giant panda habitat selection characteristics and differences using the sample data of the giant panda occurrence sites collected during 2020–2022. The results showed that the giant panda in both seasons selected medium altitudes (2000–2400 m), southeastern slopes, slopes less than 15°, taller tree layers (8–15 m) with a larger diameter at breast height (17–25 cm) and medium density (25–55%), shorter shrub layers (2 m) with high density (>35%). The giant panda microhabitat survey in the Niba Mountain corridor clarified the characteristics of suitable habitat selection for the giant panda in the corridor. The findings of the study can provide scientific references for the development of practical habitat conservation and management measures for giant pandas in the study area.

Exposure to ambient PM2.5 (fine particulate matter) can cause adverse effects on human health. China has been experiencing dramatic changes in air pollution over the past two decades. Statistically deriving ground-level PM2.5 from satellite aerosol optical depth (AOD) has been an emerging attempt to provide such PM2.5 data for environmental monitoring and PM2.5-related epidemiologic study. However, current countrywide datasets in China have generally lower accuracies with lower spatiotemporal resolutions because surface PM2.5 level was rarely recorded in historical years (i.e., preceding 2013). This study aimed to reconstruct daily ambient PM2.5 concentrations from 2000 to 2018 over China at a fine scale of 1 km using advanced satellite datasets and ground measurements. Taking advantage of the newly released Multi-Angle Implementation of Atmospheric Correction (MAIAC) 1-km AOD dataset, we developed a novel statistical strategy by establishing an advanced spatiotemporal model relying on adaptive model structures with linear and non-linear predictors. The estimates in historical years were validated against surface observations using a strict leave-one-year-out cross-validation (CV) technique. The overall daily leave-one-year-out CV R2 and root-mean-square-deviation values were 0.59 and 27.18 μg/m3, respectively. The resultant monthly (R2 = 0.74) and yearly (0.77) mean predictions were highly consistent with surface measurements. The national PM2.5 levels experienced a rapid increase in 2001–2007 and significantly declined between 2013 and 2018. Most of the discernable decreasing trends occurred in eastern and southern areas, while air quality in western China changed slightly in the recent two decades. Our model can deliver reliable historical PM2.5 estimates in China at a finer spatiotemporal resolution than previous approaches, which could advance epidemiologic studies on the health impacts of both short- and long-term exposure to PM2.5 at both a large and a fine scale in China.

Given the important role of green environments playing in healthy cities, the inequality in urban greenspace exposure has aroused growing attentions. However, few comparative studies are available to quantify this phenomenon for cities with different population sizes across a country, especially for those in the developing world. Besides, commonly used inequality measures are always hindered by the conceptual simplification without accounting for human mobility in greenspace exposure assessments. To fill this knowledge gap, we leverage multi-source geospatial big data and a modified assessment framework to evaluate the inequality in urban greenspace exposure for 303 cities in China. Our findings reveal that the majority of Chinese cities are facing high inequality in greenspace exposure, with 207 cities having a Gini index larger than 0.6. Driven by the spatiotemporal variability of human distribution, the magnitude of inequality varies over different times of the day. We also find that exposure inequality is correlated with low greenspace provision with a statistical significance (p-value

Thyroid carcinoma (TC) is one of the most prevalent primary endocrine tumors, and its incidence is steadily and gradually increasing worldwide. Accumulating evidence has revealed the critical functions of long noncoding RNAs (lncRNAs) in the tumorigenesis and development of TC. Many TC-associated lncRNAs have been documented to be implicated in TC malignant behaviors, including abnormal cell proliferation, enhanced stem cell properties and aggressiveness, and resistance to therapeutics, through interaction with proteins, DNA, or RNA or encoding small peptides. Therefore, further elucidating the lncRNA dysregulation sheds additional insights into TC tumorigenesis and progression and opens new avenues for the early diagnosis and clinical therapy of TC. In this review, we summarize the abnormal expression of lncRNA in TC and the fundamental characteristics in TC tumorigenesis and development. Additionally, we introduce the potential prognostic and therapeutic significance of lncRNAs in TC.

An amendment to this paper has been published and can be accessed via the original article.

Background: Metastasis is a major obstacle in the treatment of bladder cancer (BC). Circular RNAs exert various functions in the aggressive biological behaviour of cancers. In this study, we aimed to elucidate how circPICALM influences BC metastasis. Methods: The expression of circPICALM was analysed by real-time PCR. The tumourigenic properties of BC cells were evaluated using in vitro migration, invasion, and wound healing assays and an in vivo footpad model. The interaction between circPICALM and miR-1265 was confirmed by pull-down and dual-luciferase reporter assays and biotin-labelled miRNA capture. The interaction of STEAP4 and focal adhesion kinase (FAK) was confirmed by co-immunoprecipitation. Findings: CircPICALM was downregulated in BC tissues, and low circPICALM expression was related to advanced T stage, high grade, lymph node positivity and poor overall survival. Overexpression of circPICALM inhibited the metastasis of BC cells, and DHX9 negatively regulated circPICALM levels. CircPICALM colocalized with miR-1265 and acted as a sponge for this miRNA, and the pro-invasion effect of miR-1265 was abolished by circPICALM overexpression. STEAP4, a target of miR-1265, suppressed metastasis; it bound to FAK to prevent autophosphorylation at Y397 and influenced EMT in BC cells. Interpretation: CircPICALM can inhibit BC metastasis and bind to miR-1265 to block its pro-invasion activity. STEAP4 is a target of miR-1265 and is related to FAK phosphorylation and EMT. Fund: This research was supported by National Natural Science Foundation of China, No.81772728, National Natural Science Foundation of China, No.81772719, National Natural Science Foundation of China No.81572514. Keywords: circPICALM, miR-1265, STEAP4, EMT, Metastasis, Bladder cancer

Abstract Background Circular RNAs (circRNAs) represent a subclass of regulatory RNAs that have been shown to have significant regulatory roles in cancer progression. However, the biological functions of circRNAs in bladder cancer (BCa) are largely unknown. Methods Cell invasion models were established, and invasion-related circRNAs were detected by qPCR. Using above method, circ-ZKSCAN1 was picked out for further study. Circ-ZKSCAN1 expression and survival analyses were performed through qPCR. The survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to assess the significance. Cell proliferation, migration and invasion were examined to investigate the function of circ-ZKSCAN1. Tumorigenesis in nude mice was assessed to determine the effect of circ-ZKSCAN1 in bladder cancer. Biotin-coupled probe pull-down assays, FISH and luciferase reporter assays were conducted to confirm the relationship between circ-ZKSCAN1 and microRNA. RNA-seq revealed different molecular changes in downstream genes. Results Here, we found that circ-ZKSCAN1 was downregulated in BCa tissues and cell lines. Circ-ZKSCAN1 levels were associated with survival, tumor grade, pathological T stage and tumor recurrence. Overexpressed circ-ZKSCAN1 inhibits cell proliferation, migration, invasion and metastasis in vitro and in vivo. Mechanistically, we demonstrated that circ-ZKSCAN1 upregulated p21 expression by sponging miR-1178-3p, which suppressed the aggressive biological behaviors in bladder cancer. Conclusions These results reveal that Circ-ZKSCAN1 acts as a tumor suppressor via a novel circ-ZKSCAN1/miR-1178-3p/p21 axis, which have the important role in the proliferation, migration and invasion ablitities of BCa cells and provide a novel perspective on circRNAs in BCa progression.

Abstract Background Circular RNAs (circRNAs) have been considered to mediate occurrence and development of human cancers, generally acting as microRNA (miRNA) sponges to regulate downstream genes expression. However, the aberrant expression profile and dysfunction of circRNAs in human bladder cancer remain to be investigated. The present study aims to elucidate the potential role and molecular mechanism of circACVR2A in regulating the proliferation and metastasis of bladder cancer. Methods circACVR2A (hsa_circ_0001073) was identified by RNA-sequencing and validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The role of circACVR2A in bladder cancer was assessed both in vitro and in vivo. Biotin-coupled probe pull down assay, biotin-coupled microRNA capture, dual-luciferase reporter assay, and fluorescence in situ hybridization were conducted to evaluate the interaction between circACVR2A and microRNAs. Results The expression of circACVR2A was lower in bladder cancer tissues and cell lines. The down-regulation of circACVR2A was positively correlated with aggressive clinicopathological characteristics, and circACVR2A served as an independent risk factor for overall survival in bladder cancer patients after cystectomy. Our in vivo and in vitro data indicated that circACVR2A suppressed the proliferation, migration and invasion of bladder cancer cells. Mechanistically, we found that circACVR2A could directly interact with miR-626 and act as a miRNA sponge to regulate EYA4 expression. Conclusions circACVR2A functions as a tumor suppressor to inhibit bladder cancer cell proliferation and metastasis through miR-626/EYA4 axis, suggesting that circACVR2A is a potential prognostic biomarker and therapeutic target for bladder cancer.

Ambient exposure to fine particulate matter (PM2.5) in eastern China, a densely populated region with very high-level PM2.5 pollution, has attracted great concern from the public, government, and scientific community. By taking advantage of advanced statistical methods and a high-resolution PM2.5 dataset, this study explicitly investigated the spatiotemporal changes in PM2.5 in eastern China from 2001 to 2018 at multiple spatial and temporal scales and examined its links with natural and socioeconomic factors to explore their effects on PM2.5 changes. This study found that the PM2.5 concentration in most of eastern China declined recently, while most of the discernable decreasing trends occurred in the southern and western areas of the study domain, and the statistically significant increasing trends were primarily in the North China Plain. The influencing factors analysis found that, among the selected four natural and five anthropogenic factors, temperature, and population density exerted more potent effects than the other influencing factors, and all the influencing factors were found to impose complex effects on the PM2.5 concentration over space and time. Our study draws a complete picture of the changes in PM2.5 and its possible influences, which could guide future actions to mitigate PM2.5 pollution in eastern China.

Rapid urbanization in China has led to an increasing problem of atmospheric nitrogen dioxide (NO2) pollution, which negatively impacts urban ecology and public health. Nitrogen dioxide is an important atmospheric pollutant, and quantitative spatio-temporal analysis and influencing factor analysis of Chinese cities can help improve urban air pollution. In this study, the spatio-temporal analysis methods were used to explore the variations of NO2 pollution in Chinese cities from 2005 to 2020. The findings are as follows. In more than half of Chinese cities, NO2 levels remarkably decreased between 2005 and 2020. The effective NO2 reduction strategies contributed to the significant NO2 reduction during the 13th Five-Year Plan (2016–2020). Moreover, we found that the pandemic of COVID-19 alleviated NO2 pollution in China since it reduced the traffic, industrial, and living activities. The NO2 pollution in Chinese cities was found highly spatially clustered. The geographically and temporally weighted regression model was used to analyze the spatio-temporal heterogeneity of NO2 pollution influencing factors in Chinese cities, including natural meteorological and socio-economic factors. The results showed that the GDPPC, population densities, and ambient air pressure were positively correlated with NO2 pollution. In contrast, the ratio of the tertiary to the secondary industry, temperature, wind speed, and relative humidity negatively impacted the NO2 pollution level. The findings of this research contribute to the improvement of urban air quality, stimulating the achievements of the sustainable development goals of Chinese cities.

The Chengdu-Chongqing Economic Circle (CCEC) is becoming the fourth growth pole in China after the Yangtze River Delta Economic Circle (YRDEC); Guangdong, Hong Kong, and Macao Economic Circle (GBAEC); Beijing, Tianjin, and Hebei Economic Circle (BTHEC). The land use and landscape ecological management of the CCEC is critical to its social and economic development. Using ArcGIS modeling and Fragstats processing methods, we divided the CCEC into 5 km × 5 km ecological risk areas and constructed a landscape ecological risk index evaluation model to calculate the spatial and temporal dynamic changes in the urban expansion and landscape ecological risk over the last 20 years. The results show that the land use was mainly cultivated land, which exhibited a decreasing trend and was mainly converted to construction land and forest land. The change in the construction land exhibited a continuous expansion trend with the dual core in Chengdu-Chongqing. The average risk of 10,155 risk communities was about 0.16. The expansion of human activities increased the landscape ecological risk of the construction land, and the risk of the edge of the cultivated land was higher than the internal risk value. The ecological risk index values of 16 cities in the study area ranged from 0.02 to 0.28. The resistance of the landscape pattern to external disturbance was stronger than that in other regions of China. The landscape ecological risk is controllable overall. However, the higher level of economic development in Chengdu, Chongqing, and other mature cities poses a greater landscape ecological risk. The results of this research provide an important reference for promoting the optimization and construction of the land space in the CCEC, building ecological shelters, and preventing ecological risk in the upper reaches of the Yangtze River.

Long-term PM2.5 levels with high precision at fine spatiotemporal resolution are essential for quantitatively understanding the health risk of exposure to ambient fine particulate matter (PM2.5) and making effective air pollution control policies. The emerging statistically derived PM2.5 estimations from satellite remote sensing observations of aerosol optical depth (AOD) data are an effective alternative to reconstruct global, long-term, high spatiotemporal resolution PM2.5 information. However, studies on PM2.5 estimation and its application to exposure and health-related studies are limited in China due to the lack of historical in-situ measurements before 2013. In this study, we explored the long-term trends of PM2.5 exposure in central China, a hotspot that has recently been experiencing severe particulate pollution, at the local scale. We first developed a spatiotemporal model incorporating periodical characteristics within the data to estimate daily concentrations of historical PM2.5 at a fine scale of 1 km for 2003–2018. The linear effects of predictors including AOD, meteorological and land-use parameters and the non-linear interaction between AOD and meteorological parameters were considered in the modeling process. The most recently released high-resolution satellite aerosol product, Multi-Angle Implementation of Atmospheric Correction (MAIAC) was used to help to represent the fine-scale particle gradients. Our daily estimates correlated well with in-situ observations (cross-validation R2 = 0.59), achieving precision comparable to previous statistical models. Through linking with gridded demographic data, the population-weighted PM2.5 average during 2003 to 2018 was found to be high (62.23 μg/m3 for the whole domain) with obvious spatial variations and seasonality. An inverse U pattern was seen in the time series, with two inflection points around 2008 and 2015. Our model provides reliable particulate information with high spatial resolution and long-term temporal coverage, which can inform local-scale PM2.5-related epidemiological studies and health-risk assessments for central China. Keywords: Fine particulate matter, Satellite remote sensing, Aerosol optical depth, Spatiotemporal modeling, Long-term trend

Background: Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous unit. Many factors are involved in the occurrence of acne. It has been confirmed that some adipokines play an important role in the development of AV. Irisin is a novel adipokine, which is highly expressed in skeletal muscle, liver, and fat. It improves insulin resistance (IR) by inducing the browning of white adipose tissue, increasing heat production and energy expenditure. Objective: The purpose of this study was to investigate the role of serum irisin as an adipokine to explore its function in the pathogenesis of AV and its correlation with IR, and whether it can be used as a potential biomarker of insulin sensitivity. Although the hyperinsulinemic-euglycemic clamp remains the gold standard for accurate determination of IR, it cannot be performed routinely. Various alternative simpler measures have been used, the most common being homeostasis model assessment. However, these metrics are limited by their accuracy, cost, and blood collection requirements.[1] Therefore, an effective and feasible serum biomarker is an attractive and relatively straightforward method, which may provide clinicians with a more accurate and simple method for the prediction and diagnosis of IR. IR can often be detected before other symptoms appear, so establishing an early diagnosis method will allow for the appropriate treatment of patients before the disease develops. Patients and Methods: The study included 171 subjects; 115 patients with newly diagnosed AV and 56 apparently healthy subjects. The contents of irisin and interleukin-1 alpha in serum were determined by enzyme-linked immunosorbent assay. The IR index was calculated by the homeostasis model. Results: Serum irisin levels in AV patients and control group were (24.0 ± 11.3) and (104.3 ± 27.0) ng/dl, respectively, which were significantly lower than those in control group (P < 0.001). Serum irisin was negatively correlated with IR (r = −0.711, P 0.001). The sensitivity of irisin was 100.0%, the specificity was 92.8%, and the cutoff point was 53.32. The decrease of serum irisin level could predict the patients with IR in acne. Conclusion: Serum irisin levels in AV patients were significantly decreased. Serum irisin showed acceptable performance criteria in the diagnosis of AV with IR. Serum irisin seems to be a good diagnostic and prognostic marker for IR. Further multi-center studies are needed to confirm this link, which could pave the way for new treatment options.

Active power factor correction converters are often introduced as the front stage of power electronic equipment to improve the power factor and eliminate higher harmonics. A Boost or Buck-Boost converter operating in discontinuous current mode is always adopted to achieve high power factor correction. In addition, the input current contains a large amount of higher harmonics, and a low-pass input filter is commonly adopted to filter it out. In this paper, a single-stage high-frequency AC/AC converter is taken as an example to demonstrate the design method of a passive low-pass filter. Firstly, the input side of the grid needs to meet the power factor and harmonic requirements. The preset parameters are set to a range to characterize the performance of the LC filter. The quantitative design method of input filter is proposed and summarized. Moreover, the sensitivity of the filter parameters is analyzed, providing a direction in practical applications. Preset parameters are all proved to conform to the preset range through PSIM simulation. Finally, a 130-W prototype is established to verify the correction of proposed design method. The power factor is around 0.935 and harmonic content in the input current is about 26.4%. All requirements can be satisfied.

ARHGEF6 belongs to the family of guanine nucleotide exchange factors (GEFs) for Rho GTPases, and it specifically activates Rho GTPases CDC42 and RAC1. Arhgef6 is the X-linked intellectual disability gene also known as XLID46, and clinical features of patients carrying Arhgef6 mutations include intellectual disability and, in some cases, sensorineural hearing loss. Rho GTPases act as molecular switches in many cellular processes. Their activities are regulated by binding or hydrolysis of GTP, which is facilitated by GEFs and GTPase-activating proteins, respectively. RAC1 and CDC42 have been shown to play important roles in hair cell (HC) stereocilia development. However, the role of ARHGEF6 in inner ear development and hearing function has not yet been investigated. Here, we found that ARHGEF6 is expressed in mouse cochlear HCs, including the HC stereocilia. We established Arhgef6 knockdown mice using the clustered regularly interspaced short palindromic repeat-associated Cas9 nuclease (CRISPR-Cas9) genome editing technique. We showed that ARHGEF6 was indispensable for the maintenance of outer hair cell (OHC) stereocilia, and loss of ARHGEF6 in mice caused HC stereocilia deficits that eventually led to progressive HC loss and hearing loss. However, the loss of ARHGEF6 did not affect the synapse density and did not affect the mechanoelectrical transduction currents in OHCs at postnatal day 3. At the molecular level, the levels of active CDC42 and RAC1 were dramatically decreased in the Arhgef6 knockdown mice, suggesting that ARHGEF6 regulates stereocilia maintenance through RAC1/CDC42.

A substantial number of studies have analyzed how driving factors impact aerosols, but they have been little concerned with the spatial heterogeneity of aerosols and the factors that impact aerosols. The spatial distributions of the aerosol optical depth (AOD) retrieved by Moderate Resolution Imaging Spectrometer (MODIS) data at 550-nm and 3-km resolution for three highly developed metropolises, the Beijing-Tianjin-Hebei (BTH) region, the Yangtze River Delta (YRD), and the Pearl River Delta (PRD), in China during 2015 were analyzed. Different degrees of spatial heterogeneity of the AOD were found, which were indexed by Moran’s I index giving values of 0.940, 0.715, and 0.680 in BTH, YRD, and PRD, respectively. For the spatial heterogeneity, geographically weighted regression (GWR) was employed to carry out a spatial factor analysis, where terrain, climate condition, urban development, and vegetation coverage were taken as the potential driving factors. The results of the GWR imply varying relationships between the AOD and the factors. The results were generally consistent with existing studies, but the results suggest the following: (1) Elevation increase would more likely lead to a strong negative impact on aerosols (with most of the coefficients ranging from −1.5~0 in the BTH, −1.5~0 in the YRD, and −1~0 in the PRD) in the places with greater elevations where the R-squared values are always larger than 0.5. However, the variation of elevations cannot explain the variation of aerosols in the places with relatively low elevations (with R-squared values approximately 0.1, ranging from 0 to 0.3, and approximately 0.1 in the BTH, YRD, and PRD), such as urban areas in the BTH and YRD. (2) The density of the built-up areas made a strong and positive impact on aerosols in the urban areas of the BTH (R-squared larger than 0.5), while the R-squared dropped to 0.1 in the places far away from the urban areas. (3) The vegetation coverage led to a stronger relief on the AOD in parts of the YRD and PRD (with coefficients less than −0.6 and ranging from −0.4~−0.6, respectively) where there is greater vegetation coverage, and led to a weaker relief on the AOD in the urban area of the PRD with a coefficient of approximately −0.2~−0.4.

Moderate resolution imaging spectroradiometer (MODIS) aerosol optical depth (AOD) products have been widely used to characterize the temporal variations and spatial distributions of atmospheric aerosols. In the present study, we evaluate the performance of four Terra and Aqua MODIS Collection 6 (C6) quality assured AOD products in the Pearl River Delta (PRD) region, a humid subtropical region. The 10 km AOD products retrieved by the Dark Target (DT) and Deep Blue (DB) algorithms, the merged DT/DB (DTDB) 10 km product, and the DT 3 km AOD product were obtained for 2006–2015. These products were compared with Aerosol Robotic Network (AERONET) observations, and with each other. The Terra- and Aqua-derived AODs are quantitatively similar. However, there are significant differences among the four AOD products. The DT 10 km product correlates more closely with AERONET AOD observations than does the DB 10 km product. The latter tends to underestimate the AOD, whereas the former typically overestimates it for highly urbanized areas. The DTDB 10 km product is mainly derived from the DT 10 km product; it does not provide a gap-filled data set, because valid DB 10 km retrievals are not included in the merged product even when DT 10 km retrievals are unavailable. Therefore, the DT/DB merging protocol should be improved. The DT 3 km AOD product closely mimics the DT 10 km product; however, it contains fewer data than the DT 10 km product over water-contaminated areas. In addition, although the quality assured AOD products are recommended for use in quantitative applications by the MODIS aerosol science team, the sampling frequency of these products is generally lower than 25%. Thus, the sampling issues of these products should be considered in humid subtropical areas.

Purpose: Complex bone defects with a horizontal and vertical combined deficiency pose a clinical challenge in implant dentistry. This study reports the case of a young female patient who presented with a perforating bone defect in the aesthetic zone. Materials and methods: Based on prosthetically guided bone regeneration, virtual 3D bone augmentation was planned. A 3D printed customised titanium mesh and the autogenous bone ring technique were then utilised simultaneously to achieve a customised bone contour. After 6 months, the titanium mesh was removed and connective tissue grafting was performed. Finally, implants were placed and the provisional and definitive prostheses were delivered following a digital approach. Vertical and horizontal bone gain, new bone density, pseudo-periosteum type and marginal bone loss were measured. Planned bone volume, regenerated bone volume and regeneration rate were analysed. Results: Staged tooth shortening led to a coronal increase in keratinised mucosa. The customised titanium mesh and bone ring technique yielded 14.27 mm vertical bone gain and 12.9 mm horizontal bone gain in the perforating area. When the titanium mesh was removed, the reopening surgery showed a Type 1 pseudo-periosteum (none or < 1 mm), and CBCT scans revealed a new bone density of ~550 HU. With a planned bone volume of 1063.55 mm3, the regenerated bone volume was 969.29 mm3, indicating a regeneration rate of 91.14%. The 1-year follow-up after definitive restoration revealed no complications except for 0.55 to 0.60 mm marginal bone loss. Conclusion: Combined application of customised titanium mesh and an autogenous bone ring block shows promising potential to achieve prosthetically guided bone regeneration for complex bone defects in the aesthetic zone. [ABSTRACT FROM AUTHOR]