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Objective Multitargeted tyrosine kinase inhibitors (TKIs) have been approved as second‐line therapy in refractory sarcoma, prolonging progression‐free survival (PFS) but with short‐lived duration of disease control. Fruquintinib is a TKI that specifically inhibits vascular endothelial growth factor receptor‐1,2,3 with no metabolism by liver enzymes. In this retrospective study, we assessed the efficacy and safety of fruquintinib‐based treatment in patients with refractory sarcoma after developing several lines of TKI resistance. Methods We retrospectively analyzed the clinical data of patients with refractory sarcoma after they had developed several lines of resistance to TKIs and who received fruquintinib‐based treatment from November 2021 to August 2023. The primary endpoint was the progression‐free survival rate at 4 months (4m‐PFSR). Secondary endpoints were the median PFS, overall survival (OS), objective response rate, disease control rate, and adverse effects (AEs). PFS and OS were estimated using the Kaplan–Meier method. A log‐rank test was used to compare survival curves between different clinical and pathological factors. Cox proportional hazards analysis was performed to identify PFS‐related prognostic factors. Results We included 124 patients: 56 (45.2%) with osteosarcoma, 28 (22.6%) with Ewing sarcoma, seven (5.6%) with chondrosarcoma, and 33 (26.6%) with soft tissue sarcomas (STS). Only 18 (14.5%) patients received monotherapy with fruquintinib. With a median follow‐up time of 6.8 (interquartile range [IQR], 4.6–9.4) months, 22 (17.7%) patients had partial response and 78 (62.9%) had stable disease. The 4m‐PFSR was 58.4% (95% confidence interval [CI], 49.6%–67.1%). The median PFS and OS were 4.4 (95% CI, 3.9–5.0) months and 11.4 (95% CI, 10.3–12.5) months. In multivariate analysis, a high hazard ratio for progression was associated with target lesions located outside the lung and bone with 1.79 (95% CI, 1.10–2.93; p = 0.020). Eighty‐eight AEs were recorded in 47 (37.9%) patients; the most common were pneumothorax (18/124, 14.5%), diarrhea (8/124, 6.5%), oral mucositis (7/124, 5.6%), and thrombocytopenia (7/124, 5.6%). Conclusions Fruquintinib may be a potential option for patients with refractory sarcoma after developing several lines of TKI resistance, with a satisfactory efficacy and safety profile in combination therapy. However, the degree of contribution of fruquintinib to results is unclear when combined with other effective substances. Additional prospective trials of fruquintinib should be conducted, especially involving different pathological types and combination regimens.

Abstract The interrelationship between climate change, pollution and the aerobiome (the microbiome of the air) is a complex ecological dynamic with profound implications for human and ecosystem health. This mini‐review explores the multifaceted relationships among these factors. By synthesising existing research and integrating interdisciplinary perspectives, we examine the mechanisms driving interactions within the climate change–pollution–aerobiome nexus. We also explore synergistic and cascading effects and potential impacts on human health (including both communicable and non‐communicable diseases) and that of wider ecosystems. Based on our mini‐review results, climate change influences air pollution and, independently, air pollution affects the composition, diversity and activity of the aerobiome. However, we apply a ‘systems thinking’ approach and create a set of systems diagrams to show that climate change likely influences the aerobiome (including bacteria and fungi) via climate change–pollution interactions in complex ways. Due to the inherent complexity of these systems, we emphasise the importance of holistic and/or interdisciplinary approaches and collaborative efforts in understanding this nexus to safeguard planetary health in an era of rapid environmental change.

Abstract Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched‐chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high‐fat diet/low‐dose streptozotocin (HFD/STZ)‐induced T2DM and leptin receptor‐deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label‐free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L‐type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA‐deficiency‐induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

Abstract Background As the leading cause of end‐stage liver disease, nonalcoholic fatty liver disease (NAFLD) is mainly induced by lipid dyshomeostasis. The translation of endogenous circular RNAs (circRNAs) is closely related to the progression of various diseases, but the involvement of circRNAs in NAFLD has not been determined. Methods Combined high‐throughput circRNA profiles were used to identify circRNAs with translational potential. The underlying molecular mechanisms were investigated by RNA sequencing, pull‐down/MS and site‐specific mutagenesis. Results In this study, we focused on circ‐SLC9A6, an abnormally highly expressed circRNA in human and mouse liver tissue during NAFLD development that exacerbates metabolic dyshomeostasis in hepatocytes by encoding a novel peptide called SLC9A6‐126aa in vivo and in vitro. YTHDF2‐mediated degradation of m6A‐modified circ‐SLC9A6 was found to be essential for the regulation of SLC9A6‐126aa expression. We further found that the phosphorylation of SLC9A6‐126aa by AKT was crucial for its cytoplasmic localization and the maintenance of physiological homeostasis, whereas high‐fat stress induced substantial translocation of unphosphorylated SLC9A6‐126aa to the nucleus, resulting in a vicious cycle of lipid metabolic dysfunction. Nuclear SLC9A6‐126aa promotes transcriptional activation of the target gene CD36 and enhances its occupancy of the CD36 promoter locus by regulating MOF‐mediated histone H4K16 acetylation. Hepatic CD36 depletion significantly ameliorated hyperactivated MAPK signalling and lipid disturbance in SLC9A6‐126aa transgenic mice. Clinically, increasing levels of SLC9A6‐126aa were observed during NAFLD progression and were found to be positively correlated with the CD36 and MAPK cascades. Conclusion This study revealed the role of circ‐SLC9A6‐derived SLC9A6‐126aa in the epigenetic modification‐mediated regulation of lipid metabolism. Our findings may provide promising therapeutic targets for NAFLD and new insights into the pathological mechanisms of metabolic diseases. Highlights Under normal circumstances, driven by m6A modification, YTHDF2 directly recognizes and degrades circ‐SLC9A6, thereby inhibiting the translation of SLC9A6‐126aa. Additionally, AKT1 phosphorylates and inhibits the nuclear translocation of SLC9A6‐126aa. In NAFLD, lipid overload leads to YTHDF2 and AKT1 deficiency, ultimately increasing the expression and nuclear import of SLC9A6‐126aa. Nuclear SLC9A6‐126aa binds directly to the CD36 promoter and initiates CD36 transcription, which induces lipid dyshomeostasis.

Abstract Environmental change exerts a profound effect on soil microbial domains—including bacteria, fungi, and protists—that each perform vital ecological processes. While these microbial domains are ubiquitous and extremely diverse, little is known about how they respond to environmental changes in urban soil ecosystems and what ecological processes shape them. Here we investigated the community assembly processes governing bacteria, fungi, and protists through the lens of four distinct subcommunities: abundant, conditionally rare, conditionally abundant, and rare taxa. We show that transient taxa, including the conditionally rare and conditionally rare or abundant taxa, were the predominant subcommunities. Deterministic processes (e.g., environmental filtering) had major roles in structuring all subcommunities of fungi, as well as conditionally rare and abundant protists. Stochastic processes had strong effects in structuring all subcommunities of bacteria (except rare taxa) and conditionally rare protists. Overall, our study underscores the importance of complementing the traditional taxonomy of microbial domains with the subcommunity approach when investigating microbial communities in urban soil ecosystems.

Abstract The Seychelles magpie‐robin's (SMR) five island populations exhibit some of the lowest recorded levels of genetic diversity among endangered birds, and high levels of inbreeding. These populations collapsed during the 20th century, and the species was listed as Critically Endangered in the IUCN Red List in 1994. An assisted translocation‐for‐recovery program initiated in the 1990s increased the number of mature individuals, resulting in its downlisting to Endangered in 2005. Here, we explore the temporal genomic erosion of the SMR based on a dataset of 201 re‐sequenced whole genomes that span the past ~150 years. Our sample set includes individuals that predate the bottleneck by up to 100 years, as well as individuals from contemporary populations established during the species recovery program. Despite the SMR's recent demographic recovery, our data reveal a marked increase in both the genetic load and realized load in the extant populations when compared to the historical samples. Conservation management may have reduced the intensity of selection by increasing juvenile survival and relaxing intraspecific competition between individuals, resulting in the accumulation of loss‐of‐function mutations (i.e. severely deleterious variants) in the rapidly recovering population. In addition, we found a 3‐fold decrease in genetic diversity between temporal samples. While the low genetic diversity in modern populations may limit the species' adaptability to future environmental changes, future conservation efforts (including IUCN assessments) may also need to assess the threats posed by their high genetic load. Our computer simulations highlight the value of translocations for genetic rescue and show how this could halt genomic erosion in threatened species such as the SMR.

Abstract An accurate quantification of global methane sources and sinks is imperative for assessing realistic pathways to mitigate climate change. A key challenge of quantifying the Global Methane Budget (Saunois et al., 2020, https://doi.org/10.5194/essd‐12‐1561‐2020) is the lack of consistency in uncertainties between sectors. Here we provide a new perspective on bottom‐up (BU) and top‐down (TD) methane uncertainties by using an expert opinion analysis based on a questionnaire conducted in 2021. Expectedly, experts rank highest uncertainty and lowest confidence levels in the Global Methane Budget related to natural sources in BU budgets. Here, we further reveal specific uncertainty types and introduce a ranking system for uncertainties in each sector. We find that natural source uncertainty is related particularly to driver data uncertainty in freshwater, vegetation, and coastal/ocean sources, as well as parameter uncertainty in wetland models. Reducing uncertainties, most notably in aquatic and wetland sources will help balance future BU and TD global methane budgets. We suggest a new methane source partitioning over gradients of human disturbance and demonstrate that 76.3% (75.8%–79.4%) or 561 (443–700) Tg CH4 yr−1 of global emissions can be attributed to moderately impacted, man‐made, artificial, or fully anthropogenic sources and 23.7% (20.6%–24.2%) or 174 (115–223) Tg CH4 yr−1 to natural and low impacted methane sources. Finally, we identify current research gaps and provide a plan of action to reduce current uncertainties in the Global Methane Budget.

Abstract Moxibustion has been shown to have a potential antihypertensive effect, but its applicability for the primary care of hypertension is unclear. The authors conducted a multicenter randomized controlled trial (RCT) with patient preference arms to investigate the effect, safety, cost‐effectiveness, and compliance of moxibustion in community patients with hypertension. Patients with primary hypertension were enrolled from seven communities randomly or nonrandomly assigned to receive self‐administered moxibustion + the original hypertensive regimen or the original hypertensive regimen alone for 6 months. The authors mainly evaluated the effects of moxibustion on hypertensive outcomes and adverse events. As a result, a total of 160 and 240 patients were recruited into the randomized and nonrandomized arms, respectively, with 87.5% completing the follow‐up. At month 6, there was a significantly greater reduction in systolic blood pressure (SBP) (difference: −10.57 mmHg), a higher proportion of responders (82.2% vs. 53.7%; odds ratio 4.00), and better improvements in hypertensive symptoms and quality of life (QoL) in the moxibustion group than in the control group in the randomized population, but there was no significant between‐group difference in diastolic blood pressure (DBP). The nonrandomized findings showed the same effect direction for all outcomes, except for DBP. All moxibustion‐related adverse events were mild. In conclusion, moxibustion can reduce SBP and improve hypertensive symptoms and QoL in community patients with hypertension, with good safety and low cost, although its effect on DBP remains uncertain. The findings suggest that moxibustion may be an appropriate technique for community primary care of hypertension.

Abstract Background The current utilization of neurokinin‐1 receptor antagonists (NK1RAs) and the impact of updated guidelines on prescription patterns of antiemetic drugs among Chinese patients receiving highly emetogenic chemotherapy (HEC) remain undetermined. This study aims to analyze the present situation of Chinese cancer patients using antiemetic drugs and assess the appropriateness of antiemetic regimens. Methods Prescription data were collected between January 2015 and December 2020 from cancer patients receiving cisplatin‐based chemotherapy at 76 hospitals in six major cities in China. Trends in the use of antiemetic drugs, prescribing patterns and adherence to antiemetic guidelines were assessed. Results Among the 108,611 patients included in this study, 6 classes and 17 antiemetic drugs were identified as monotherapy or combination therapy in 93,872 patients (86.4%), whereas 14,739 patients (13.6%) were administered no antiemetic treatment. 5‐hydroxytryptamine 3 receptor antagonists (5‐HT3RAs) and glucocorticoids were the two most frequently used classes of antiemetics, followed by metoclopramide. NK1RAs were underused across the six cities, only 9332 (8.6%) and 1655 (1.5%) cisplatin‐based treatments were prescribed aprepitant and fosaprepitant, respectively. Prescriptions of olanzapine and lorazepam were very low throughout the study period. In prescribing patterns of antiemetic drugs, dual combination regimens were the most common (40.0%), followed by triple combination therapy and monotherapy (25.8% and 15.1%, respectively). Overall, the adherence to antiemetic guidelines for patients undergoing cisplatin‐based regimens was only 8.1% due to inadequate prescription of antiemetic drugs. Finally, our study also revealed that 5‐HT3RAs and glucocorticoids were overprescribed in 8.8% and 1.6% of patients, respectively. Conclusions The current study reveals suboptimal utilization of recommended antiemetic drugs for managing cisplatin‐based HEC‐induced nausea and vomiting in China. Improving the management of CINV is crucial, and these findings provide valuable insights into optimizing antiemetic drug practices.

Atopic dermatitis is one of the most common dermatologic problems, especially in children. Given the ability of symbiotic microorganisms in modulating the immune system, probiotics administration has been studied in previous research in the management of atopic dermatitis. However, there are conflicting results between studies. In this study, we aimed to assess the effectiveness of mixed probiotics as a treatment option for atopic dermatitis induced by ovalbumin. BALB/c juvenile mice were classified and divided into the ovalbumin group, mixed probiotic group (ovalbumin + LK), and control group. Except for the control group, all mice were sensitized with ovalbumin to establish a model of atopic dermatitis. The mixed probiotics were given by gavage for 14 days. Mice body weight, skin lesions, skin inflammation, ovalbumin-specific Ig, the number of Treg and CD103+DC, and the expression level of PD-1/PD-L1 were examined. The results showed that mixed probiotics can improve body weight and alleviate skin symptoms. Mixed probiotics reduced serum Th2 inflammatory factors, eosinophils, mast cell degranulation, mast cell count, and the expression of ovalbumin-specific immunoglobulin E/G1 and increased the anti-inflammatory cytokine interleukin-10, Treg cells, CD103+DC cells, and the expression level of PD-1/PD-L1. These findings suggest that mixed probiotics could be a viable treatment option for atopic dermatitis and provide insight into the underlying mechanisms involved.

To describe the microtrajectory change behavior of two-wheeled vehicles when encountering nonrigid obstacles, this paper proposes an obstacle avoidance model of two-wheeled vehicles for nonrigid obstacles based on the improved social force method. In the model, the obstacle avoidance characteristics of two-wheeled vehicles for nonrigid obstacles and the safety operation requirements of two-wheeled vehicles are considered. The calculation methods of the minimum boundary distance of avoidance and the boundary avoidance force range edge function are proposed based on the ultimate turning angle and boundary avoidance characteristics, respectively. The speed control and direction control behavior of the rider to the vehicle is abstracted as the form of social force, and the two-wheeled vehicle/rider individual is subjected to the avoidance force and correction force perpendicular to the direction of the longitudinal axis of the vehicle body. The centrifugal trajectory obstacle avoidance motion obeying the Newtonian mechanics is studied based on the characteristics of the vehicle body turning angle change. Different traffic environments are constructed by MATLAB software and simulated according to the model running logic, and sensitivity analysis is performed based on the actual data collected in the survey. The simulation results show that, under the same conditions, compared with μi = 50N, when μi = 200N, the X-axis displacement of the simulated vehicle in the avoidance process is shortened by 26.31%, and the body deflection angle increases by 50.75% at the end moment of the avoidance process. Compared with electric motorcycles, the displacement of the X-axis in the avoidance process of the electric bicycle is shortened by 16.92%, and the body deflection angle at the end moment of the avoidance process is increased by 13.68%. The simulation results show that the model can well describe the trajectory change behavior characteristics of two-wheeled vehicles/riders encountering nonrigid obstacles in real situations, and the obstacle avoidance model of two-wheeled vehicles proposed in this paper is considered to be traffic justified.

Abstract Aims Proton pump inhibitors (PPI) are widely used for gastroesophageal varices in patients with cirrhosis after endoscopic therapy, although the effect of PPI on these patients remains controversial. This study aimed to evaluate the effect of PPI on gastroesophageal varices in patients with cirrhosis after endoscopic therapy, including variceal bleeding and adverse events. Methods Cirrhotic patients with endoscopically confirmed gastroesophageal varices were enrolled in this study between May 2017 and June 2019. Eligible patients were randomized into two groups: one group received PPI for 14 days and the other group did not receive PPI treatment (n = 53 in each group). All patients were followed for 8 weeks. Results During the follow‐up period, three patients (5.66%) in the PPI group experienced variceal bleeding on days 9, 16, and 25 after endoscopic therapy, including two patients with acute bleeding and one with primary prophylaxis. In the non‐PPI group, three patients (5.66%) experienced variceal bleeding on days 7, 42, and 56 after endoscopic therapy, including one patient with acute bleeding and two with secondary prophylaxis (p = 0.990). The incidence of adverse events was similar between the two groups (37.74% vs. 28.30%, p = 0.30). Conclusions PPI did not appear to reduce variceal bleeding and adverse events in patients with cirrhosis after endoscopic therapy.

Objectives The fact that studies on anti‐programmed cell death 1 (PD‐1) or its relevant ligand 1 (PD‐L1) have yielded such few responses greatly decreases the confidence in immunotherapy with checkpoint inhibitors for advanced osteosarcoma. We intended to characterize the expression of various checkpoint molecules with immunohistochemistry in osteosarcoma specimens and analyzed the relationship of the expression of these checkpoint molecules with patients' clinical courses. Methods This study was a retrospective non‐intervention study from August 1st 2017 to March 1st 2020. Immunohistochemistry for B7‐H3 (CD276, Cluster of Differentiation 276), CD47 (Cluster of Differentiation 47), PD‐L1 (programmed cell death ligand 1), TIM3 (mucin‐domain containing‐3), TGF‐β (TransformingGrowth Factor β), CXCR 4 (Chemokine Receptor 4), CD27 (Cluster of Differentiation 27), IDO1 (Indoleamine 2,3‐dioxygenase 1), KIRs (Killer cell Immunoglobulin‐like Receptors), and SDF‐1 (Stromal cell‐Derived Factor‐1) was performed on 35 resected osteosarcoma specimens. Patients progressed upon first‐line chemotherapy with evaluable lesions were qualified for this study, and their specimens previously stored in the pathological department repository would be retrieved for analysis. Associations between the immunohischemistry markers and clinicopathological variables and survival were evaluated by the χ2 displayed by cross‐table, Cox proportional hazards regression model, and Kaplan–Meier plots. Results The positive rates of B7‐H3, CD47, PD‐L1, TIM3, and TGF‐β expression in this sample of 35 heavily treated osteosarcomas were 29% (10/35), 15% (5/35), 9% (3/35), 6% (2/35), and 6% (2/35), respectively, and diverse staining intensities were observed. Among these advanced patients, 15/35 (43%) had positive checkpoint expression, of which 33% (5/15) showed evidence of the co‐expression of more than one checkpoint molecule. We did not find any obvious correlation with clinicopathological characteristics and the positive expression of these molecules. Conclusions The present study highlights that only a small subset of progressive osteosarcomas, which had been heavily‐treated, expressed tumor immune‐associated checkpoint molecules, of which B7‐H3 was the most positively expressed checkpoint and might be a promising target for further osteosarcoma investigation.

Abstract Background Insulin‐like growth Factor 2 mRNA‐binding protein 3 (IGF2BP3) is a highly conserved RNA‐binding protein and plays a critical role in regulating posttranscriptional modifications. Methods Immunoprecipitation was used to examine the interaction of Parkin and IGF2BP3. Mass spectrometry was performed to identify the ubiquitination sites of IGF2BP3. RNA‐immunoprecipitation was conducted to examine the target genes of IGF2BP3. Xenograft mouse model was constructed to determine the tumorigenesis of IGF2BP3. Results IGF2BP3 expression is negatively correlated with Parkin expression in human cervical cancer cells and tissues. Parkin directly interacts with IGF2BP3, and overexpression of Parkin causes the proteasomal degradation of IGF2BP3, while knockdown of PARK2 increases the protein levels of IGF2BP3. Mechanistically, in vivo and in vitro ubiquitination assays demonstrated that Parkin is able to ubiquitinate IGF2BP3. Moreover, the ubiquitination site of IGF2BP3 was identified at K213 in the first KH domain of IGF2BP3. IGF2BP3 mutation results in the loss of its oncogenic function as an m6A reader, resulting in the inactivation of the phosphoinositide 3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK) signalling pathways. In addition, IGF2BP3 mutation results in the attenuation of Parkin‐mediated mitophagy, indicating its inverse role in regulating Parkin. Consequently, the tumourigenesis of cervical cancer is also inhibited by IGF2BP3 mutation. Conclusion IGF2BP3 is ubiquitinated and regulated by the E3 ubiquitin ligase Parkin in human cervical cancer and ubiquitination modification plays an important role in modulating IGF2BP3 function. Thus, understanding the role of IGF2BP3 in tumourigenesis could provide new insights into cervical cancer therapy.

Abstract The taxonomic status of the now likely extirpated Korean Peninsula wolf has been extensively debated, with some arguing it represents an independent wolf lineage, Canis coreanus. To investigate the Korean wolf's genetic affiliations and taxonomic status, we sequenced and analysed the genomes of a Korean wolf dated to the beginning of the 20th century, and a captive wolf originally from the Pyongyang Central Zoo. Our results indicated that the Korean wolf bears similar genetic ancestry to other regional East Asian populations, therefore suggesting it is not a distinct taxonomic lineage. We identified regional patterns of wolf population structure and admixture in East Asia with potential conservation consequences in the Korean Peninsula and on a regional scale. We find that the Korean wolf has similar genomic diversity and inbreeding to other East Asian wolves. Finally, we show that, in contrast to the historical sample, the captive wolf is genetically more similar to wolves from the Tibetan Plateau; hence, Korean wolf conservation programmes might not benefit from the inclusion of this specimen.

Abstract Global change is affecting soil biodiversity and functioning across all terrestrial ecosystems. Still, much is unknown about how soil biodiversity and function will change in the future in response to simultaneous alterations in climate and land use, as well as other environmental drivers. It is crucial to understand the direct, indirect and interactive effects of global change drivers on soil communities and ecosystems across environmental contexts, not only today but also in the near future. This is particularly relevant for international efforts to tackle climate change like the Paris Agreement, and considering the failure to achieve the 2020 biodiversity targets, especially the target of halting soil degradation. Here, we outline the main frontiers related to soil ecology that were presented and discussed at the thematic sessions of the World Biodiversity Forum 2022 in Davos, Switzerland. We highlight multiple frontiers of knowledge associated with data integration, causal inference, soil biodiversity and function scenarios, critical soil biodiversity facets, underrepresented drivers, global collaboration, knowledge application and transdisciplinarity, as well as policy and public communication. These identified research priorities are not only of immediate interest to the scientific community but may also be considered in research priority programmes and calls for funding.

Abstract Background Combining antiangiogenic therapy with radioimmunotherapy is believed to further improve antitumor efficacy, but there is still a lack of evidence to support this. This study aimed to investigate the role of the tumor vascular‐targeted agent famitinib with a combination of radiotherapy and an immune checkpoint inhibitor in murine lung cancer. Methods The effect of VEGFA and HIF1A on clinical prognosis and the tumor immune microenvironment was analyzed using public databases. Enrichment analyses of post‐irradiation gene expression and mRNAs related to immunotherapy efficacy were carried out based on GEO datasets. A C57BL/6 mouse subcutaneous tumor model was used to evaluate the antitumor effects of different treatment schemes. The tumor immunophenotyping was identified by flow cytometry. Results We demonstrated that high level of VEGFA and HIF1A expression in lung cancer was related to poor prognosis and immunosuppressive tumor microenvironment. In a mouse model, the triple therapy of famitinib, radiotherapy and immunotherapy had the most dramatic antitumor activity. It significantly increased tumor infiltrating lymphocytes and reversed the immunosuppressive state of the tumor microenvironment in mice. Compared with radioimmunotherapy, the addition of famitinib further promoted the infiltration of CD8+ T cells and M1 type tumor associated macrophages, and reduced the number of myeloid suppressor cells. Therefore, triple therapy converted the immunosuppressive tumor microenvironment into an immunostimulatory one. Conclusion Famitinib can synergize with radioimmunotherapy by regulating the tumor immune microenvironment in murine lung cancer.

Objective The adequate management of asymptomatic osteoporotic vertebral burst fractures (OVBFs) was still controversial. Percutaneous vertebroplasty (PVP) could achieve quick recovery with minor trauma, but there were certain safety problems by traditional bone cement injection method. Thus, the aim of this study was to assess the efficacy of lateral‐opening injection tool used in PVP treating patients with asymptomatic OVBFs. Methods This was a retrospective study of OVBFs treated in our institute from March 2016 to March 2020. A total of 66 patients (mean age 72.10 ± 7.98 years, with 21 men and 45 women) who were diagnosed with acute asymptomatic OVBFs with mild spinal canal compromise were treated with PVP by using a lateral‐opening injection tool. Two puncture needles were simultaneously placed transpedicularly in the fractured vertebra, and the inner core was removed, and the lateral‐opening injection tool was inserted. The adjustment of lateral hole was to improve the distribution height of bone cement and avoid the entry of bone cement into the posterior wall of vertebral body. Related clinical outcomes and images were assessed, including back pain (visual analog scale [VAS]), vertebral height ratio (fractured vertebral height/average adjacent nonfractured vertebral height), kyphosis Cobb angle, union of the fractured vertebral posterior wall, distribution of bone cement, surgical data, and complications. Results The average follow‐up time of all cases was 21.23 ± 9.35 months. The mean amount of bone cement was 3.28 ± 0.35 ml in the vertebrae and the mean operative time was 34.02 ± 5.23 min. There were 60 cases of bone cement that contacted the upper and lower endplates on at least one side. There was no cement leakage into the spinal canal or fracture displacement of the posterior wall of the vertebral body in all cases. The VAS scores were 3.78 ± 0.42 at 1 day postoperatively and 0.53 ± 0.40 at the last follow‐up, significantly lower than 8.40 ± 0.48 preoperatively (p

Objective Hallux valgus (HV) is a common foot deformity, and recurrence is one of the most serious complications after HV correction. As a result, the surgical technique with a lower recurrence rate is a dream. The purpose of the article should be to observe the correction effect of hallux valgus using a novel “V‐cut” osteotomy on the first metatarsal head combined with fixation in mortise‐shaped bone groove‐plasty technique. Methods Twenty‐three consecutive patients (40 feet) with HV were included from March 2019 to May 2020, who were all treated using single screw fixation with V‐cut osteotomy on the first metatarsal head combined with mortise‐shaped metatarsal bone groove‐plasty and Akin osteotomy on the first toe for hallux valgus correction. With a mean follow‐up time of 21.7 months, the visual analogue scale (VAS) score and American Orthopedic Foot and Ankle Society (AOFAS) forefoot score and the changes of the hallux valgus angle (HVA), intermetatarsal angle (IMA) and distal metatarsal articular angle (DMAA) were evaluated during the clinical follow‐up. The paired t test was used for analytical statistics. Results The VAS score improved from 6.78 ± 1.74 to 1.87 ± 1.45 and the AOFAS score improved from 53.9 ± 12.3 preoperatively to 94.7 ± 6.8 in the latest follow‐up postoperatively (P

Objective Currently, there is a lack of good clinical tools for evaluating the effect of chemotherapy preoperatively on primary high‐grade bone sarcomas. Our goal was to investigate the predictive value of the clinical findings and establish a scoring system to predict chemotherapy response. Methods We conducted a retrospective multicenter cohort study and reviewed 322 patients with primary high‐grade bone sarcomas. Patients who routinely received neoadjuvant chemotherapy and underwent primary tumor resection with an assessment of tumor necrosis rate (TNR) were enrolled in this study. The medical records of patients were collected from November 1, 2011, to March 1, 2018, at Peking University People's Hospital (PKUPH) and Peking University Shougang Hospital (PKUSH). The mean age of the patients was 16.2 years (range 3–52 years), of whom 65.5% were male. The clinical data collected before and after neoadjuvant chemotherapy included the degree of pain, laboratory inspection, X‐ray, CT, contrast‐enhanced magnetic resonance (MR), and positron emission tomography‐computed tomography (PET‐CT). Several machine learning models, including logistic regression, decision trees, support vector machines, and neural networks, were used to classify the chemotherapy responses. Area under the curve (AUC) of the scoring system to predict chemotherapy response is the primary outcome measure. Results For patients without events, a minimum follow‐up of 24 months was achieved. The median follow‐up time was 43.3 months, and it ranged from 24 to 84 months. The 5 years progression‐free survival (PFS) of the included patients was 54.1%. The 5 years PFS rate was 39.7% for poor responders and 74.9% for good responders. Features such as longest diameter reduction ratio (up to three points), clear bone boundary formation (up to two points), tumor necrosis measured by magnetic resonance (up to two points), maximum standard uptake value (SUVmax) decrease (up to three points), and significant alkaline phosphatase decrease (up to 1 point) were identified as significant predictors of good histological response and constituted the scoring system. A score ≥4 predicts a good response to chemotherapy. The scoring system based on the above factors performed well, achieving an AUC of 0.893. For nonmeasurable lesions (classified by the revised Response Evaluation Criteria in Solid Tumors [RECIST 1.1]), the AUC was 0.901. Conclusion We first devised a well‐performing comprehensive scoring system to predict the response to neoadjuvant chemotherapy in primary high‐grade bone sarcomas.

Abstract Introduction To explore the role of IL‐6/JAK/STAT signaling in tubal infertility. Methods The fimbriae tissues of 14 patients with a history of infertility and hydrosalpinx and 14 patients with no history of infertility and no fallopian tube disease were collected. The tissues were then divided into hydrosalpinx group and control group followed by analysis of the protein expression of key factors in the IL‐6/JAK/STAT signaling by immunohistochemistry and Western blot. Results Immunohistochemical staining showed significantly higher level of IL‐6, JAK1, p‐JAK1, JAK2, p‐JAK2, STAT1, p‐STAT1, STAT3, and p‐STAT3 in hydrosalpinx group than those in control group with IL‐6 being mainly located in the cytoplasm and p‐JAK2, STAT1, p‐STAT1, STAT3, and p‐STAT3 in the cytoplasm and nucleus. JAK1 and p‐JAK1 was mainly located in the cytoplasm and JAK2 is in the cytoplasm and nucleus without difference of their expression between two groups. Consistently, hydrosalpinx group presented significantly higher protein levels of IL‐6, JAK1, p‐JAK1, JAK2, p‐JAK2, STAT1, p‐STAT1, STAT3, and p‐STAT3 than control group without difference of JAK1, p‐JAK1, JAK2 level. Conclusion The activation of IL‐6/JAK2/STAT1 and STAT3 signaling pathways are found in the hydrosalpinx in infertile patients, indicating that they might be involved in the pathogenesis of hydrosalpinx.

Abstract Bronze phase TiO2 [TiO2(B)] has great research potential for sodium storage since it has a higher theoretical capacity and ion mobility compared with other phases of TiO2. In this case, preparing porous TiO2(B) nanosheets, which can provide abundant sodium insertion channels, is the most effective way to improve transport kinetics. Here, we use the strong one‐dimensional TiO2 nanowires as the matrix for stringing these nanosheets together through a simple solvothermal method to build a bunchy hierarchical structure [TiO2(B)‐BH], which has fast pseudocapacitance behavior, high structural stability, and effective ion/electron transport. With the superiorities of this structure design, TiO2(B)‐BH has a higher capacity (131 vs. 70 mAh g−1 [TiO2‐NWs] at 0.5 C). And it is worth mentioning that the reversible capacity of up to 500 cycles can still be maintained at 85 mAh g−1 at a high rate of 10 C. Meanwhile, we also further analyzed the sodium storage mechanism through the ex‐situ X‐ray powder diffraction test, which proved the high structural stability of TiO2(B)‐BH in the process of sodiumization/de‐sodiumization. This strategy of uniformly integrating nanosheets into a matrix can also be extended to preparing electrode material structures of other energy devices.

Abstract Oxide‐based photoelectrodes commonly generate deep trap states associated with various intrinsic defects such as vacancies, antisites, and dislocations, limiting their photoelectrochemical properties. Herein, it is reported that rhombohedral GaFeO3 (GFO) thin‐film photoanodes exhibit defect‐inactive features, which manifest themselves by negligible trap‐states‐associated charge recombination losses during photoelectrochemical water splitting. Unlike conventional defect‐tolerant semiconductors, the origin of the defect‐inactivity in GFO is the strongly preferred antisite formation, suppressing the generation of other defects that act as deep traps. In addition, defect‐inactive GFO films possess really appropriate oxygen vacancy concentration for the oxygen evolution reaction (OER). As a result, the as‐prepared GFO films achieve the surface charge transfer efficiency (ηsurface) of 95.1% for photoelectrochemical water splitting at 1.23 V versus RHE without any further modification, which is the highest ηsurface reported of any pristine inorganic photoanodes. The onset potential toward the OER remarkably coincides with the flat band potential of 0.43 V versus RHE. This work not only demonstrates a new benchmark for the surface charge transfer yields of pristine metal oxides for solar water splitting but also enriches the arguments for defect tolerance and highlights the importance of rational tuning of oxygen vacancies.

Abstract Background For patients with ypN2 non‐small cell lung cancer (NSCLC) after neoadjuvant chemotherapy followed by surgery (NCS), the role of postoperative radiotherapy (PORT) is unclear. The aim of our study was to evaluate the effect of PORT on survival of ypN2 NSCLC patients after NCS. Methods Between 2004 and 2015, patients with ypN2 NSCLC after NCS were filtrated from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was used to balance the baseline characteristics of the PORT and non‐PORT groups. Kaplan–Meier method and Cox proportional hazards models were adopted to estimate overall survival (OS) and cancer‐specific survival (CSS). Results A total of 257 patients who met the criteria were included in the study. After PSM, 115 patients remained in each group. The survival of patients in the PORT group was significantly better than those in the non‐PORT group. Median OS was 36 months vs. 26 months, and 5‐year OS rate was 40.5% vs. 21.0% (p = 0.002). The median CSS was 38 months vs. 27 months, and the 5‐year CSS rate was 43.7% vs. 22.1% (p 3. Conclusions For patients with ypN2 NSCLC after NCS, PORT significantly improves OS and CSS. These results need to be confirmed by further randomized studies.

Abstract Currently, it is difficult for China's electricity trading platform to handle large amounts of data during centralized clearing, achieve cross‐regional sharing of transaction information, and realize the optimized allocation of resources. The previous research has proposed establishing a new distributed electricity market trading platform based on blockchain technology to solve the aforementioned problems; however, transaction nodes on the platform have difficulty determining the final delisting plan in the face of numerous choices. Therefore, in this study, a search engine was designed according to the demands of the delisting node. The developed algorithm is run with a programmed script through a smart contract and can provide the best delisting plan for delisting nodes, ensuring that the delisting plan is selected intelligently and publicly. Overall, seven delisting strategies were designed. Additionally, the improved Critic‐G1 method based on the coefficient of variation was used to establish a smart contract for the comprehensive evaluation of listing nodes. Finally, the example analysis verified that calling the smart contract can help the delisting node quickly obtain the best delisting strategy, increase the enthusiasm of the transaction subject, and facilitate the promotion and application of the transaction platform based on blockchain technology, confirming the effectiveness of the proposed method.

Abstract Methane (CH4) is inexpensive, high in heating value, relatively low in carbon footprint compared to coal, and thus a promising energy resource. However, the locations of natural gas production sites are typically far from industrial areas. Therefore, transportation is needed, which could considerably increase the sale price of natural gas. Thus, the development of distributed, clean, affordable processes for the efficient conversion of CH4 has increasingly attracted people's attention. Among them are plasma technology with the advantages of mild operating conditions, low space need, and quick generation of energetic and chemically active species, which allows the reaction to occur far from the thermodynamic equilibrium and at a reasonable cost. Significant progress in plasma‐assisted reforming of methane (PARM) is achieved and reviewed in this paper from the perspectives of reactor development, thermal and nonthermal PARM routes, and catalysis. The factors affecting the conversion of reactants and the selectivity of products are studied. The findings from the past works and the insight into the existing challenges in this work should benefit the further development of reactors, high‐performance catalysts, and PARM routes.

Pulmonary arterial hypertension is a progressive and fatal disease and rodents with experimental pulmonary hypertension (PH) are often used to study pathogenic mechanisms, identify therapeutic targets, and develop novel drugs for treatment. Here we describe a hands‐on set of experimental approaches including ex vivo lung angiography and histology and in vivo right heart catheterization (RHC) to phenotypically characterize pulmonary hemodynamics and lung vascular structure in normal mice and mice with experimental PH. We utilized Microfil polymer as contrast in our ex vivo lung angiogram to quantitatively examine pulmonary vascular remodeling in mice with experimental PH, and lung histology to estimate pulmonary artery wall thickness. The peripheral lung vascular images were selected to determine the total length of lung vascular branches, the number of branches and the number of junctions in a given area (mm−2). We found that the three parameters determined by angiogram were not significantly different among the apical, middle, and basal regions of the mouse lung from normal mice, and were not influenced by gender (no significant difference between female and male mice). We conducted RHC in mice to measure right ventricular systolic pressure, a surrogate measure for pulmonary artery systolic pressure and right ventricle (RV) contractility (RV ± dP/dtmax) to estimate RV function. RHC, a short time (4–6 min) procedure, did not alter the lung angiography measurements. In summary, utilizing ex vivo angiogram to determine peripheral vascular structure and density in the mouse lung and utilizing in vivo RHC to measure pulmonary hemodynamics are reliable readouts to phenotype normal mice and mice with experimental PH. Lung angiogram and RHC are also reliable approaches to examine pharmacological effects of new drugs on pulmonary vascular remodeling and hemodynamics.

Abstract Background and purpose We aimed to analyze the influence of target‐related and clinical factors on lung tumor motion based on four‐dimensional CT (4DCT), and clarify the motion based on subgroups in lung stereotactic body radiation therapy. Materials and methods 4DCT image data of 267 tumors from 246 patients were analyzed. The coordinates in the left–right (LR), anterior–posterior (AP), and cranial–caudal (CC) directions of the center of mass (COM) of the gross tumor volumes in 10 phases of 4DCT were measured. The peak‐to‐peak COM displacement in the LR, AP, CC, and 3D directions was calculated. The influence of target‐related and clinical factors on tumor motion was evaluated using multivariate analysis. Results The tumor segment location correlated with the tumor motion in each direction. Tumor size was predictive of tumor motion in the 3D (p = 0.023) and AP directions (p = 0.049). The tumor motion for metastatic tumors was smaller than that for primary tumors in the LR (p = 0.019) and AP directions (p = 0.008). The CC motion for pulmonary surgery recipients (3.8 ± 4.5 mm) was less than that for patients who had not undergone surgery (5.6 ± 5.4 mm), and no significant clinical factor was observed. BSA and BMI were positively correlated with the motion in the CC (p = 0.02) and LR directions (p = 0.002). Conclusion The tumor segment location was a good predictor of tumor motion. A larger tumor tends to have a smaller motion. Patients with metastatic tumors or those who have undergone pulmonary surgery exhibited smaller and more unpredictable tumor motions, which required individual assessments. Thus, clinical factors can potentially predict tumor motion.

Abstract Objective Adenomyosis is characterized by the presence of endometrium or endometrium‐like glands and stroma within the myometrium. In this study, we aimed to investigate whether the cGAS–STING pathway was activated and correlated with clinical outcomes in adenomyosis patients. Materials and Methods Twenty patients diagnosed with adenomyosis and 10 patients diagnosed with cervical intraepithelial neoplasia grade 3 (CIN‐3) but no adenomyosis were enrolled in this study. Specimens were collected during surgery from August 2017 to December 2017 at Third Xiangya Hospital. The messenger RNA (mRNA) and protein levels of key cGAS–STING pathway factors in uterine tissue were detected by real‐time reverse‐transcription polymerase chain reaction and immunohistochemistry, respectively. The correlations of gene expression and clinical outcomes, including dysmenorrhea and uterine volume, were analyzed. Results The cGAS, STING, TANK‐binding kinase 1 (TBK‐1), interferon‐α (IFN‐α), IFN‐β, and tumor necrosis factor‐α (TNF‐α) mRNA and protein levels in the ectopic endometrial tissue from adenomyosis patients were significantly higher compared with that from the controls in endometrium (p

Abstract Since the reformation of the electricity market of China is increasing and the modernization of the national governance system is being promoted, the electricity market management system needs to be gradually improved. Credit evaluation is an essential part of the electricity market management system. Therefore, a complete credit evaluation system plays a fundamental role in ensuring that the electricity market can operate safely, stably, efficiently, and reliably. The traditional credit evaluation methods focus on the financial situation and credit records of the generating companies. With the gradual development of the electricity market transactions, the market behavior needs to be included in the credit evaluation indicator system to standardize the behavior of the generating companies and reduce the risks of the market transactions. This study establishes a complete credit evaluation system from three perspectives: market behavior, financial situation, and social responsibility. In addition, to determine the weight of indicators in the credit evaluation, the analytic hierarchy process (AHP) algorithm, fuzzy theory, and the non‐dominated sorted genetic algorithm II (NSGA‐II) algorithm are combined. The variance of the evaluation results and the deviation degree of the indicator weight are considered the objective functions of the NSGA‐II algorithm to optimize the indicator weight. Finally, comparing as an example the results of the credit evaluation before and after the optimization of an electricity market shows that the credit evaluation method can effectively distinguish the generating companies that adopt different market behaviors and has a high practical significance.

Abstract Spinal cord injury (SCI) is a destructive traumatic disease of the central nervous system without satisfying therapy efficiency. Bone marrow mesenchymal stem cells (BMMSCs) therapy promotes the neurotrophic factors’ secretion and axonal regeneration, thereby promoting recovery of SCI. Pulsed electromagnetic fields (PEMF) therapy has been proven to promote neural growth and regeneration. Both BMMSCs and PEMF have shown curative effects for SCI; PEMF can further promote stem cell differentiation. Thus, we explored the combined effects of BMMSCs and PEMF and the potential interaction between these two therapies in SCI. Compared with the SCI control, BMMSCs, and PEMF groups, the combinational therapy displayed the best therapeutic effect. Combinational therapy increased the expression levels of nutritional factors including brain‐derived neurotrophic factor (BDNF), nerve growth factors (NGF) and vascular endothelial growth factor (VEGF), enhanced neuron preservation (NeuN and NF‐200), and increased axonal growth (MBP and myelin sheath). Additionally, PEMF promoted the expression levels of BDNF and VEGF in BMMSCs via Wnt/β‐catenin signaling pathway. In summary, the combined therapy of BMMSCs and PEMF displayed a more satisfactory effect than BMMSCs and PEMF therapy alone, indicating a promising application of combined therapy for the therapy of SCI.

Abstract Background In this study, we aimed to investigate the association between postoperative radiotherapy (PORT) and cardiac‐related mortality in patients with stage IIIA‐N2 non‐small cell lung cancer (NSCLC) using the Surveillance, Epidemiology, and End Results (SEER) database. Methods The United States (US) population based on the SEER database was searched for cardiac‐related mortality among patients with stage IIIA‐N2 NSCLC. Cardiac‐related mortality was compared between the PORT and Non‐PORT groups. Accounting for mortality from other causes, Fine and Gray's test compared cumulative incidences of cardiac‐related mortality between both groups. Univariate and multivariate analysis were performed using the competing risk model. Results From 1988 to 2016, 7290 patients met the inclusion criteria: 3386 patients were treated with PORT and 3904 patients with Non‐PORT. The five‐year overall incidence of cardiac‐related mortality was 3.01% in the PORT group and 3.26% in the Non‐PORT group. Older age, male sex, squamous cell lung cancer, earlier year of diagnosis and earlier T stage were independent adverse factors for cardiac‐related mortality. However, PORT use was not associated with an increase in the hazard for cardiac‐related mortality (subdistribution hazard ratio [SHR] = 0.99, 95% confidence interval [CI]: 0.78–1.24, p = 0.91). When evaluating cardiac‐related mortality in each time period, the overall incidence of cardiac‐related mortality was decreased over time. There were no statistically significant differences based on PORT use in all time periods. Conclusions With a median follow‐up of 25 months, no significant differences were found in cardiac‐related mortality between the PORT and Non‐PORT groups in stage IIIA‐N2 NSCLC patients.

Abstract Aims/Introduction To evaluate gestational weight gain (GWG) in the first and second trimester as a risk factor for gestational diabetes mellitus (GDM) among women pregnant with singletons. Materials and Methods This was a cohort study of women with singleton pregnancies who delivered between 1 January 2013 and 31 October 2014 in a Chinese hospital. We collected data from medical records from the first antenatal visit to delivery. All pregnant women were subjected to an oral glucose tolerance test for diagnosis of GDM during the second trimester. GWG in the first and second trimester was calculated by subtracting the prepregnancy weight from weight within 4 weeks of the oral glucose tolerance test. We categorized GWG into insufficient, appropriate and excessive according to the Institute of Medicine guidelines and population quantiles. Univariable and multivariable analyses were used to determine the association between GWG and GDM risk. Results Of 10,422 pregnant women, we identified 8,356 eligible women with 1,622 (19.4%) diagnosed with GDM. Univariable analysis showed that GWG that exceeded the Institute of Medicine recommendation might be associated with risk of GDM (P P90 vs P10–P90 adjusted odds ratio 1.31, [95% confidence interval 1.12–1.52]; >P95 vs P5‐P95 adjusted odds ratio 1.45 [95% confidence interval 1.16–1.81]). Conclusions Excessive GWG in the first and second trimester might be a risk factor for GDM, which highlights the importance of appropriate weight gain during pregnancy.

Abstract Altitudinal changes in the diversity of plants and animals have been well documented; however, soil animals received little attention in this context and it is unclear whether their diversity follows general altitudinal distribution patterns. Changbai Mountain is one of few well‐conserved mountain regions comprising natural ecosystems on the Eurasian continent. Here, we present a comprehensive analysis of the diversity and community composition of Collembola along ten altitudinal sites representing five vegetation types from forest to alpine tundra. Among 7834 Collembola individuals, 84 morphospecies were identified. Species richness varied marginally significant with altitude and generally followed a unimodal relationship with altitude. By contrast, the density of Collembola did not change in a consistent way with altitude. Collembola communities changed gradually with altitude, with local habitat‐related factors (soil and litter carbon‐to‐nitrogen ratio, litter carbon content, and soil pH) and climatic variables (precipitation seasonality) identified as major drivers of changes in Collembola community composition. Notably, local habitat‐related factors explained more variation in Collembola assemblages than climatic variables. The results suggest that local habitat‐related factors including precipitation and temperature are the main drivers of changes in Collembola communities with altitude. Specifically, soil and litter carbon‐to‐nitrogen ratio correlated positively with Collembola communities at high altitudes, whereas soil pH correlated positively at low altitudes. This documents that altitudinal gradients provide unique opportunities for identifying factors driving the community composition of not only above‐ but also belowground invertebrates.

Background Lung cancer serum tumor markers including carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21‐1), and carbohydrate antigen 125(CA125) as prognostic predictors is controversial. Therefore, this study aimed to evaluate the association between these markers and the survival of patients with postoperative stage III‐N2 non‐small cell lung cancer (NSCLC). Methods We enrolled 1011 patients with pathologically confirmed stage III‐N2 NSCLC who underwent resection and whose pretreatment serum tumor marker levels were available. Patients were categorized according to their serum levels into low‐, medium‐, and high‐risk groups. Overall survival (OS), progression‐free survival (PFS), local regional relapse‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were calculated from the date of resection. Their association with each serum tumor marker was assessed using the log‐rank test. Results Abnormal CEA levels were associated with worse five‐year OS, PFS and DMFS; abnormal CYFRA21‐1 levels were associated with worse five‐year OS and LRFS; and abnormal CA125 levels were associated with worse five‐year OS, PFS, LRFS and DMFS. Among the risk groups, there were significant differences in five‐year OS, PFS, LRFS and DMFS (P = 0.000). In propensity score matching analysis, the model also achieved prognostic significance for all four survival classifications (P = 0.001–0.004) among the three risk groups. Conclusions The combined model achieved prognostic significance for all survival outcome types. The serum tumor markers tested are useful prognostic predictors for postoperative NSCLC patients but not for all survival outcomes. The combination of the three indices is more reliable in predicting all four of the survival outcomes. Key points Significant findings of the study Serum CEA, CYFRA21‐1, and CA125 levels can be used as prognostic factors of postoperative N2 non‐small cell lung cancer patients but not for all survival outcomes, suggesting that combinative detection of all three indices would be more reliable. What this study adds Our model utilizes available technology, with conventional cutoff values, inexpensive costs, and simple mathematics methods and, thus, can be feasibly employed by clinicians or oncologists.

Abstract Although targeting DNA repair signaling pathways has emerged as a promising therapeutic for skin cancer, the relevance of DNA damage responses (DDR) in the development and survival of nonmelanoma skin cancer (NMSC), the most common type of skin cancer, remains obscure. Here, we report that Src‐associated substrate during mitosis of 68 kDa (Sam68), an early signaling molecule in DDR, is elevated in skin tumor tissues derived from NMSC patients and skin lesions from Gli2‐transgenic mice. Downregulation of Sam68 impacts the growth and survival of human tumor keratinocytes and genetic ablation of Sam68 delays the onset of basal cell carcinomas (BCC) in Gli2‐transgenic mice. Moreover, Sam68 plays a critical role in DNA damage‐induced DNA repair and nuclear factor kappa B (NF‐κB) signaling pathways in keratinocytes, hence conferring keratinocyte sensitivity to DNA damaging agents. Together, our data reveal a novel function of Sam68 in regulating DDR in keratinocytes that is crucial for the growth and survival of NMSC.

Abstract Aims/Introduction Pregnant women with gestational diabetes mellitus (GDM) are at a higher risk of adverse pregnancy outcomes. The aim of the present study was to estimate the pooled prevalence of GDM in mainland China according to International Association of Diabetes and Pregnancy Study Groups criteria. Materials and Methods We carried out a systematic review by searching both English and Chinese literature databases. Random effects models were used to summarize the prevalence of GDM in mainland China. Subgroup and sensitivity analyses were carried out to address heterogeneity. Publication bias was evaluated using Egger's test. Results A total of 25 papers were included in the meta‐analysis, involving 79,064 Chinese participants. The total incidence of GDM in mainland China was 14.8% (95% confidence interval 12.8–16.7%). Subgroup analysis showed that the age, bodyweight and family history of diabetes mellitus could significantly increase the incidence of GDM. Conclusions To the best of our knowledge, this systematic review is the first to estimate the pooled prevalence of GDM among women in mainland China according to International Association of Diabetes and Pregnancy Study Groups criteria. The results of our systematic review suggest a high prevalence of GDM in mainland China, indicating that this country might have the largest number of GDM patients worldwide.

Abstract Intraplaque hemorrhage (IPH) plays a major role in the aggressive progression of vulnerable plaque, leading to acute cardiovascular events. We previously demonstrated that sonodynamic therapy (SDT) inhibits atherosclerotic plaque progression. In this study, we investigated whether SDT could also be applied to treat more advanced hemorrhagic plaque and addressed the underlying mechanism. SDT decreased atherosclerotic burden, positively altered atherosclerotic lesion composition, and alleviated iron retention in rabbit hemorrhagic plaques. Furthermore, SDT reduced iron retention by stimulating ferroportin 1 (Fpn1) expression in apolipoprotein E (ApoE)−/− mouse plaques with high susceptibility to IPH. Subsequently, SDT inhibited iron‐overload‐induced foam‐cell formation and pro‐inflammatory cytokines secretion in vitro. Moreover, SDT reduced levels of the labile iron pool and ferritin expression via the reactive oxygen species (ROS)‐nuclear factor erythroid 2‐related factor 2 (Nrf2)‐FPN1 pathway. SDT exerted therapeutic effects on hemorrhagic plaques and reduced iron retention via the ROS‐Nrf2‐FPN1 pathway in macrophages, thereby suggesting that it is a potential translational strategy for patients with advanced atherosclerosis in clinical practice.

This article constructs a comprehensive evaluation index system from four aspects: economic vitality, innovation efficiency, green development, and people’s lives. Use the entropy method to comprehensively measure the urban competitiveness level of 25 counties and cities in the economic zone, clarify the differences in their high-quality development levels, and use spatial econometric analysis methods to study the spatial agglomeration and dispersion and spatial convergence of regional urban competitiveness. The results show that the following: (1) the overall high-quality development level of the Huaihe River Eco-Economic Zone is not high, and the overall time and space characteristics is “high in the east and low in the west”; (2) there is a positive spatial autonomy in urban competitiveness and the spatial distribution of the Huaihe River, and relevantly, the degree of closeness of spatial associations between cities is generally low; (3) the gap between the level of urban competitiveness in Jiangsu Province is shrinking, the development of other provinces has a time lag effect, and there are differences in the level of urban competitiveness. Finally, to promote the high-quality development of the Huaihe Economic Zone, we must follow the law of the basin and the characteristics of spatial distribution and implement targeted strategies.

Objective. To explore the characteristics of invasive pulmonary fungal disease and the spectrum of pathogens causing invasive pulmonary fungal disease diagnosed by pathological examination using fungal stains. Methods. Patients with an invasive pulmonary fungal disease diagnosed by histopathological analysis through the use of fungal stains (including Grocott’s methenamine silver and periodic acid-Schiff stains) were included in this study. The clinical records, radiological reports, pathology, and fungal culture results were reviewed. Results. Forty-eight invasive pulmonary fungal disease patients diagnosed by histopathological analysis in the Tianjin Haihe Hospital (including 8 cases obtained by pulmonary resection, 35 cases by fiberoptic bronchoscopic biopsy, and 5 cases by percutaneous lung biopsy) were included. There were 24 male and 24 female patients, aged 21–80 years (53 ± 13 years). There were 37 cases of pulmonary aspergillosis, 4 cases of pulmonary cryptococcosis, 2 cases of pulmonary mucormycosis, and 5 in which pathogens were not determined due to limited tissue availability. Among 48 cases, 32 specimens were submitted to fungal culture. No fungus was detected in culture, although 26 cases of fungus infections were diagnosed by histopathological analysis. Only 3 cases were consistent between histopathological and culture results. In 3 cases, the pathogen was identified as Aspergillus spp. by the histopathological analysis, while the contrasting fungal culture results identified Candida albicans. Conclusion. Candida albicans pneumonia was rare, while aspergillosis was common in invasive pulmonary fungal disease diagnosed by histopathological analysis. The majority of patients with an invasive pulmonary fungal disease were culture-negative. Although culture can clarify the fungal pathogen species, it has low sensitivity. Pathological examination with fungal stains has its advantages in diagnosing fungal disease; therefore, more attention should be paid to the role of pathological examination in the diagnosis of fungal disease.

The decomposition-based algorithm, for example, multiobjective evolutionary algorithm based on decomposition (MOEA/D), has been proved effective and useful in a variety of multiobjective optimization problems (MOPs). On the basis of MOEA/D, the MOEA/D-DE replaces the simulated binary crossover (SBX) operator with differential evolution (DE) operator, which is used to enhance the diversity of the solutions more effectively. However, the amplification factor and the crossover probability are fixed in MOEA/D-DE, which would lead to a low convergence rate and be more likely to fall into local optimum. To overcome such a prematurity problem, this paper proposes three different adaptive operators in DE with crossover probability and amplification factors to adjust the parameter settings adaptively. We incorporate these three adaptive operators in MOEA/D-DE and MOEA/D-PaS to solve MOPs and many-objective optimization problems (MaOPs), respectively. This paper also designs a sensitive experiment for the changeable parameter η in the proposed adaptive operators to explore how η would affect the convergence of the proposed algorithms. These adaptive algorithms are tested on many benchmark problems, including ZDT, DTLZ, WFG, and MaF test suites. The experimental results illustrate that the three proposed adaptive algorithms have better performance on most benchmark problems.

In order to study the coal pillar stability of gob-side entry in gently inclined coal seam, a comprehensive method including theoretical analysis, numerical modeling, and field monitoring was applied to study its fracturing and instability mechanism. The results show that the uneven horizontal stress was the internal cause of entry asymmetric deformation and failure in inclined coal seam. In gently inclined coal seam, the rotation movement of the main roof and stress distribution were closely related to inclination of the coal seam. Based on the asymmetric deformation characteristics and mechanisms of entry, a collaborative control technology of roof cutting for pressure relief and support strengthening has been put forward. The research results have practical significance for revealing the mechanism of entry damage in gently inclined coal seam mining and proposing engineering measures to prevent coal pillar damage and disaster occurrence.

This paper uses the data of Shanghai and Shenzhen A-share-listed companies from 2008 to 2018 to construct the director networks as an indicator to explore the relationship between the company’s director networks and the cost of equity capital and the influence of nature of property rights and the ownership structure on the aforementioned relationship. The research results demonstrate that director networks cannot effectively reduce the cost of equity capital. This conclusion verifies the “busy director hypothesis.” With the increase in the director networks centrality, the increase in the cost of equity capital in non-state-owned listed companies is more significant compared with state-owned listed companies; equity concentration plays a significant negative regulatory role in the director networks centrality and affects the cost of equity capital. Compared with the networks centrality of independent director, the networks centrality of nonindependent director has a stronger negative effect on the cost of equity capital. This article broadens the perspective of corporate governance research and provides new ideas for listed companies to make financing decisions.

Objective. To systematically study the mechanism of cordyceps cicadae in the treatment of diabetic nephropathy (DN) with the method of network pharmacology and molecular docking analysis, so as to provide theoretical basis for the development of new drugs for the treatment of DN. Methods. TCMSP, Symmap, PubChem, PubMed, and CTD database were used to predict and screen the active components and therapeutic targets for DN. The network of active components and targets was drawn by Cytoscape 3.6.0, the protein-protein interaction (PPI) was analyzed by the STRING database, and the DAVID database was used for the enrichment analysis of intersection targets. Molecular docking studies were finished by Discovery Studio 3.5. Results. A total of 36 active compounds, including myriocin, guanosine, and inosine, and 378 potential targets of cordyceps cicadae were obtained. PPI network analysis showed that AKT1, MAPK8, and TP53 and other targets were related to both cordyceps cicadae and DN. GO and KEGG pathway analysis showed that these targets were mostly involved in R-HSA-450341, 157.14-3-3 cell cycle, and PDGF pathways. Docking studies suggested that myriocin can fit in the binding pocket of two target proteins (AKT1 and MAPK8). Conclusion. Active ingredients of cordyceps cicadae such as myriocin may act on DN through different targets such as AKT1, MAPK8, and TP53 and other targets, which can help to develop innovative drugs for effective treatment of DN.

Abstract Background Autophagy is an intracellular degradation pathway conserved in eukaryotes. ANXA6 (annexin A6) belongs to a family of calcium‐dependent membrane and phospholipid‐binding proteins. Here, we identify ANXA6 as a newly synthesized protein in starvation‐induced autophagy and validate it as a novel autophagy modulator that regulates autophagosome formation. Results ANXA6 knockdown attenuates starvation‐induced autophagy, while restoration of its expression enhances autophagy. GO (gene ontology) analysis of ANXA6 targets showed that ANXA6 interacts with many RAB GTPases and targets endocytosis and phagocytosis pathways, indicating that ANXA6 exerts its function through protein trafficking. ATG9A (autophagy‐related 9A) is the sole multispanning transmembrane protein and its trafficking through recycling endosomes is an essential step for autophagosome formation. Our results showed that ANXA6 enables appropriate ATG9A+ vesicle trafficking from endosomes to autophagosomes through RAB proteins or F‐actin. In addition, restoration of ANXA6 expression suppresses mTOR (mammalian target of rapamycin) activity through the inhibition of the PI3K (phosphoinositide 3‐kinase)‐AKT and ERK (extracellular signal‐regulated kinase) signaling pathways, which is a negative regulator of autophagy. Functionally, ANXA6 expression is correlated with LC3 (microtubule‐associated protein 1 light chain 3) expression in cervical cancer, and ANXA6 inhibits tumorigenesis through autophagy induction. Conclusions Our results reveal an important mechanism for ANXA6 in tumor suppression and autophagy regulation.

Background. This prospective study compared the success rate and safety of a distal transradial artery (dTRA) approach to that of the conventional transradial artery (TRA) for coronary angiography or percutaneous coronary intervention. Methods. From January 2019 to April 2020, nine hundred consecutive patients (height

In the process of denoising color images, it is very important to enhance the edge and texture information of the images. Image quality can usually be improved by eliminating noise and enhancing contrast. Based on the adaptive wavelet threshold shrinkage algorithm and considering structural characteristics on the basis of color image denoising, this paper describes a method that further enhances the edge and texture details of the image using guided filtering. The use of guided filtering allows edge details that cannot be discriminated in grayscale images to be preserved. The noisy image is decomposed into low-frequency and high-frequency subbands using discrete wavelets, and the contraction function of threshold shrinkage is selected according to the energy in the vicinity of the wavelet coefficients. Finally, the edge and texture information of the denoised color image are enhanced by guided filtering. When the guiding image is the original noiseless image itself, the guided filter can be used as a smoothing operator for preserving edges, resulting in a better effect than bilateral filtering. The proposed method is compared with the adaptive wavelet threshold shrinkage denoising algorithm and the bilateral filtering algorithm. Experimental results show that the proposed method achieves superior color image denoising compared to these conventional techniques.

Due to the influence of nonlinearity and time-variation, it is difficult to establish an accurate model of a magnetorheological damping structure that adopts semiactive control. Fuzzy control is a relatively appropriate control method, but fuzzy control design is susceptible to human subjective experience, which will decrease the control effect. This paper proposes new fuzzy control rules based on a genetic algorithm (GA) and particle swarm optimization (PSO) and performs a numerical simulation for a three-layer reinforced concrete frame structure under conditions of an uncontrolled structure, fuzzy control, fuzzy control optimized by GA, fuzzy control optimized by PSO, and GA-optimized FLC control (GA-FLC) proposed by Ali and Ramaswamy (2008). The results show that (1) the fitness values of the convergence of the two types of optimized fuzzy control are close. The speed of the convergence of the fuzzy control optimized by PSO is faster than that of the fuzzy control optimized by GA, but its running speed is slower. (2) Comparing the acceleration and displacement of the structure under the conditions of three different seismic waves, the effect of the optimized fuzzy control is better than that of the human experience fuzzy control and GA-FLC.