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Abstract Objective Closure surgery of patent foramen ovale (PFO) has been found to effectively control cryptogenic stroke and migraine, but it is uncertain whether PFO closure could also alleviate epileptic seizures. This study aims to observe the therapeutic effect of PFO closure on epileptic seizures. Methods Since July 11th, 2017, in the neurology department of West China Hospital, Sichuan University, Chengdu, we have been regularly monitoring patients with epilepsy who have undergone PFO closure. The patient's clinical information, such as frequency, duration, and severity of seizures, before and after surgery was recorded in detail as well as postoperative safety events. Results Of the 31 epilepsy patients who confirmed PFO observed (27 cases were drug‐resistant epilepsy, 87.10%), average age of surgery was 23.74 years, and 12 cases were female (38.71%). After one‐year follow‐up, 26 patients (83.87%) achieved remission of seizure frequency, and 22 of whom (70.97%) experienced a remission of more than 50%. Additionally, compared to before surgery, 22 cases (70.97%) reported a decrease in the average seizure duration, and 20 cases (64.52%) reported a reduction in seizure severity. In the seizure indicators of frequency, average duration and severity, significant differences were identified between preoperative and postoperative comparisons with all test p values were

Abstract Hepatocellular carcinomas (HCCs) are characterized by a vast spectrum of somatic copy number alterations (CNAs); however, their functional relevance is largely unknown. By performing a genome‐wide survey on prognosis‐associated focal CNAs in 814 HCC patients by an integrative computational framework based on transcriptomic data, genomic amplification is identified at 8q24.13 as a promising candidate. Further evidence is provided that the 8q24.13 amplification‐driven overexpression of Rab GTPase activating protein TBC1D31 exacerbates HCC growth and metastasis both in vitro and in vivo through activating Epidermal growth factor receptor (EGFR) signaling. Mechanistically, TBC1D31 acts as a Rab GTPase activating protein to catalyze GTP hydrolysis for Rab22A and then reduces the Rab22A‐mediated endolysosomal trafficking and degradation of EGFR. Notably, overexpression of TBC1D31 markedly increases the resistance of HCC cells to lenvatinib, whereas inhibition of the TBC1D31‐EGFR axis can reverse this resistance phenotype. This study highlights that TBC1D31 at 8q24.13 is a new critical oncogene, uncovers a novel mechanism of EGFR activation in HCC, and proposes the potential strategies for treating HCC patients with TBC1D31 amplification or overexpression.

Abstract This study investigates the specific circulation anomalies that have sustained the low Antarctic sea ice state since 2016. Firstly, we find a significant strengthening and southward shift in the Ferrel Cell (FC) during 2016–2022, resulting in a marked increase in southward transport of heat and moisture. Secondly, this enhanced FC is closely associated with a stronger mid‐latitude wave pattern. This pattern is zonally asymmetric and greatly amplifies the poleward advections of heat and moisture, leading to the increased downward longwave radiation, more liquid precipitation and sea ice retreat in specific regions, including the western Pacific and Indian Ocean sectors, Ross and northern Weddell Seas. The mechanism deduced from the short‐term period is further supported by the results of 40 ensemble members of simulations. The southward expansion of the FC and sea ice decline are closely linked to La Niña‐like conditions but may also be driven by anthropogenic global warming.

Abstract The current reliability criterion (RC) of the film capacitor (FC) is usually a fixed value, which does not consider the staged capacitance loss caused by moisture diffusion under high temperature and/or high humidity. The expected lifetime of capacitors would deviate far from the actual one. The moisture diffusion process of the encapsulated FC is analysed based on Fick's second law. In order to investigate the capacitance loss and moisture diffusion characteristics, 4 types of film capacitors are stressed with AC voltage under different temperatures and humidities. Based on the staged analysis of the capacitance and weight gain curves, the effect of moisture diffusion on capacitance loss is revealed. Results indicate that the linear stage of capacitance loss corresponds to the Fickian moisture diffusion stage of weight gain. The effect of voltage on FC aging is the most significant. The capacitance loss rate increases by 301% when the voltage rises by 30%. An RC calculation method of the FC is further proposed, which could also screen the encapsulation quality and shorten the aging test duration by at least 80%.

Abstract Background Lymph node metastasis (LNM) significantly impacts the prognosis of individuals diagnosed with cervical cancer, as it is closely linked to disease recurrence and mortality, thereby impacting therapeutic schedule choices for patients. However, accurately predicting LNM prior to treatment remains challenging. Consequently, this study seeks to utilize digital pathological features extracted from histopathological slides of primary cervical cancer patients to preoperatively predict the presence of LNM. Methods A deep learning (DL) model was trained using the Vision transformer (ViT) and recurrent neural network (RNN) frameworks to predict LNM. This prediction was based on the analysis of 554 histopathological whole‐slide images (WSIs) obtained from Qilu Hospital of Shandong University. To validate the model's performance, an external test was conducted using 336 WSIs from four other hospitals. Additionally, the efficiency of the DL model was evaluated using 190 cervical biopsies WSIs in a prospective set. Results In the internal test set, our DL model achieved an area under the curve (AUC) of 0.919, with sensitivity and specificity values of 0.923 and 0.905, respectively, and an accuracy (ACC) of 0.909. The performance of the DL model remained strong in the external test set. In the prospective cohort, the AUC was 0.91, and the ACC was 0.895. Additionally, the DL model exhibited higher accuracy compared to imaging examination in the evaluation of LNM. By utilizing the transformer visualization method, we generated a heatmap that illustrates the local pathological features in primary lesions relevant to LNM. Conclusion DL‐based image analysis has demonstrated efficiency in predicting LNM in early operable cervical cancer through the utilization of biopsies WSI. This approach has the potential to enhance therapeutic decision‐making for patients diagnosed with cervical cancer.

Abstract Objective This study aimed to investigate the proportion of patent foramen ovale (PFO) in people with epilepsy (PWE) compared to controls without epilepsy and to assess whether PWEs with and without PFO exhibit distinctive clinical features. Methods This is a case–control study conducted in a hospital. Contrast transthoracic echocardiography with a venous microbubble bolus and provocative maneuvers (Valsalva and coughing) were used to identify PFO and its right‐to‐left shunt (RLS) among 741 PWEs and 800 controls without epilepsy. The risk of having PFO in PWEs was explored using multiple matching methods and logistic regression with adjusted congenital factors that may affect the occurrence of PFO. Results The proportion of PFO in PWEs and controls was 39.00% and 24.25%, respectively. After 1:1 propensity score matching, the risk of suffering PFO in PWEs was 1.71 times (OR, 1.71; 95% CI, 1.24–2.36) higher than that in controls. PWEs also had a higher risk of having a high RLS grade (βepilepsy = 0.390, P

Objective Bone cement leakage is a major complication of percutaneous vertebroplasty (PVP) while treating Kümmell's disease and it is a focus of close attention during the surgical procedure. The study aimed to investigate whether pre‐injecting a composite of bone cement and gelatine sponge (the “bone cement‐gelatine sponge composite”) before injecting bone cement during PVP aids in lowering the leakage rate in stage I and II Kümmell's disease. Methods This prospective analysis evaluated 74 patients with stage I and II Kümmell's disease who underwent PVP treatment at our hospital from December 2019 to December 2021. The participants were divided randomly into groups based on whether the bone cement‐gelatine sponge composite was used during the surgery. The two groups were the bone cement‐gelatine sponge composite group (GS group, comprising 37 patients) and the no bone cement‐gelatine sponge composite group (N‐GS group, comprising 37 patients). The independent samples t‐test and chi‐square test were employed to compare general information, operative time, cement injection volume, intraoperative bleeding, and bone cement leakage between the two groups. Additionally, the visual analogue scale (VAS) score, Oswestry disability index (ODI), anterior vertebral height ratio (AVHR), and the kyphotic Cobb angle were compared between the two groups at the preoperative, 2 days postoperative, and 6 months postoperative stages using repeated measures analysis of variance. Results All patients were followed up for more than 6 months, with an average of (11.19 ± 2.21) months. No significant differences were observed in terms of the operative time, cement injection volume, and intraoperative bleeding between the two groups (P > 0.05). The incidence of bone cement leakage in the N‐GS group (32.43%) was significantly higher than that in the GS group (5.41%), and the difference was statistically significant (P 0.05). Conclusion The bone cement‐gelatine sponge composite intravertebral prefilling technique can lower bone cement leakage in stage I and II Kümmell's disease and can also relieve pain and improve vertebral body height.

Abstract The development of a high‐current DC breaker is very important for the protection of the expensive superconducting magnet. A kind of an economic switch called pyrobreaker, which is driven by explosive detonation waves, has been used as the backup quench protection due to its inherent reliability and fast response. A prototype pyrobreaker with a special structure that can withstand and break 100 kA is discussed. The numerical material model is taken to calculate the fracture demand of contact and the mass demand of explosive. Then, the detonation wave and contact breaking process are simulated by the ANSYS software. The performance of the design and characterisation during dynamic breaking are compared with simulation and no‐load experiment test. At the end, the temperature rise test and the breaking test under 100 kA are completed successfully. These results demonstrate that the design of 100 kA pyrobreaker is reliable.

Abstract Problem Interferon epsilon (IFN‐ε) is constitutively expressed in the epithelium of female reproductive tract and confers vital protection against sexually transmitted pathogens in mouse models. However, there is limited insight into the role of IFN‐ε in human sexually transmitted infections such as human papillomavirus (HPV). Method of Study Cervical biopsies were obtained from high‐risk (HR) HPV positive (n = 28) and HR‐HPV negative (n = 10) women. mRNA expression of IFN‐ε in cervical tissues was measured by qPCR. Expression of the IFN‐ε protein was determined by Western blot analysis, immunohistochemistry and immunofluorescence staining. Results mRNA expression of IFN‐ε was higher in the ectocervix than that of other IFNs, and was further upregulated in HR‐HPV positive women compared with HR‐HPV negative women. Expression of the IFN‐ε protein was comparable between HR‐HPV infected patients and healthy controls. Conclusions These results reveal differential expression of IFN‐ε mRNA between individuals with or without HR‐HPV infection, and imply direct or indirect regulatory mechanisms for IFN‐ε transcription by HPV. Expression of IFN‐ε protein in HPV infections would require further validation.

Abstract Background Graves' disease (GD) is a T cell‐mediated organ‐specific autoimmune disease. Forkhead box P3 (FoxP3) is an excellent marker for the induction and development of regulatory T cells (Tregs). Recent studies showed that single‐nucleotide polymorphisms (SNPs) in the FoxP3 gene were associated with the increased susceptibility to several autoimmune diseases. In the present study, we investigated the association of FoxP3 gene polymorphisms with GD in a Southwest Chinese Han population. Methods A two‐stage case‐control study was performed in 890 healthy controls (male, 282; female, 608) and 503 patients with GD (male, 138; female, 365). Four SNPs (rs3761548, rs3761549, rs3761547, and rs2280883) were genotyped by the polymerase chain reaction‐restriction fragment length polymorphism assay. The χ2 test was used to compare the genotype distributions and allele frequencies between GD patients and healthy controls. Results In the first stage, the significantly increased frequencies of the A allele (p = .031, odds ratio [OR] = 1.635) and AA genotype (p = .023, OR = 3.257), together with a significantly decreased frequency of the C allele (p = .031, OR = 0.611) of FoxP3/rs3761548 were found in female patients with GD. None of the other FoxP3 SNPs was associated with GD susceptibility. Subsequent validation and combination of data confirmed the association between FoxP3/rs3761548 and the female patients with GD (A allele: p < .001, OR = 1.672; AA genotype: p = .005, OR = 2.488; CC genotype: p = .001, OR = 0.622; C allele: p < .001, OR = 0.615, respectively). Conclusion Our findings suggest that FoxP3/rs3761548 is significantly associated with female GD patients in a Southwest Chinese Han population.

Abstract Computer‐assisted orthopedic system (CAOS) is rapidly gaining popularity in the field of precision medicine. However, the cost‐effectiveness of CAOS has not been well clarified. We performed this review to summarize and assess the cost‐effectiveness analyses (CEAs) with regard to CAOS. Publications on CEA in CAOS have been searched in PubMed and CEA Registry up to May 31, 2022. The Quality of Health Economic Studies (QHES) instrument was used to estimate the quality of studies. Relationships between qualities and potential factors were also examined. There were 15 eligible studies in the present review. Twelve studies evaluated CAOS joint arthroplasties and found that CAOS joint arthroplasties were cost‐effective compared to manual methods. Three studies focused on spinal surgery, two of which analyzed the cost‐effectiveness of CAOS for patients after spinal fusion, with conflicting results. One study demonstrated that CAOS was cost‐effective in spinal pedicle screw insertion. The mean QHES score of CEAs included was 86.1. The potential factors had no significant relationship with the quality of studies. Based on available studies, our review reflected that CAOS was cost‐effective in the field of joint arthroplasty. While in spinal surgery, the answer was unclear. Current CEAs represent high qualities, and more CEAs are required in the different disciplines of orthopedics where CAOS is employed.

Objective The mechanical high modulus structure of the proximal femur could guide clinical surgical treatment and instrument design of proximal femoral fractures. The purpose of this study is to analyze and verify the mechanical structure of the proximal femur. Methods A total of 375 patients with intertrochanteric fractures were imaged using computed tomography (CT) scans. Patients were grouped according to age and sex. Cortical and medullary cavity parameters (cortical thickness [CTh], cortical mean density [CM], upper‐lower diameter length [ULL], and medial‐lateral diameter length [MLL]) were measured at eight planes. Six proximal femoral finite element models of different sexes and ages were constructed. To verify the measurement results, Abaqus was used to implement the force load to describe the von Mises stress distribution, and the maximum von Mises stress values of each wall of the proximal femur were compared. Results The CTh values of the lower and upper walls were higher than those of the anterior and posterior walls of the femoral neck (p

Abstract There is emerging evidence that α1‐blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1‐blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1‐blockers as add‐on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1‐blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1‐blockers have to be used under several considerations. Among the currently available agents, only long‐acting α1‐blockers, such as doxazosin gastrointestinal therapeutic system 4–8 mg daily and terazosin 2–4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1‐blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1‐blocker with a diuretic.

Abstract Background SIRT6, an important NAD+‐dependent protein, protects endothelial cells from inflammatory and oxidative stress injuries. However, the role of SIRT6 in cardiac microvascular endothelial cells (CMECs) under ischemia‒reperfusion injury (IRI) remains unclear. Methods The HUVECs model of oxygen–glucose deprivation/reperfusion (OGD/R) was established to simulate the endothelial IRI in vitro. Endoplasmic reticulum oxidase 1 alpha (Ero1α) mRNA and protein levels in SIRT6‐overexpressing or SIRT6‐knockdown cells were measured by qPCR and Western blotting. The levels of H2O2 and mitochondrial reactive oxygen species (ROS) were detected to evaluate the status of oxidative stress. The effects of SIRT6 deficiency and Ero1α knockdown on cellular endoplasmic reticulum stress (ERS), inflammation, apoptosis and barrier function were detected by a series of molecular biological experiments and functional experiments in vitro. Chromatin immunoprecipitation, Western blotting, qPCR, and site‐specific mutation experiments were used to examine the underlying molecular mechanisms. Furthermore, endothelial cell‐specific Sirt6 knockout (ecSirt6−/−) mice were subjected to cardiac ischemia‒reperfusion surgery to investigate the effects of SIRT6 in CMECs in vivo. Results The expression of Ero1α was significantly upregulated in SIRT6‐knockdown endothelial cells, and high Ero1α expression correlated with the accumulation of H2O2 and mitochondrial ROS. In addition, SIRT6 deficiency increased ERS, inflammation, apoptosis and endothelial permeability, and these effects could be significantly attenuated by Ero1α knockdown. The deacetylase catalytic activity of SIRT6 was important in regulating Ero1α expression and these biological processes. Mechanistically, SIRT6 inhibited the enrichment of HIF1α and p300 at the Ero1α promoter through deacetylating H3K9, thereby antagonizing HIF1α/p300‐mediated Ero1α expression. Compared with SIRT6‐wild‐type (SIRT6‐WT) cells, cells expressing the SIRT6‐H133Y‐mutant and SIRT6‐R65A‐mutant exhibited increased Ero1α expression. Furthermore, ecSirt6−/− mice subjected to ischemia‒reperfusion surgery exhibited increased Ero1α expression and ERS in CMECs and worsened injuries to microvascular barrier function and cardiac function. Conclusions Our results revealed an epigenetic mechanism associated with SIRT6 and Ero1α expression and highlighted the therapeutic potential of targeting the SIRT6‐HIF1α/p300‐Ero1α axis.

Abstract Background The careHPV test as a primary screening method for cervical cancer has been proven to be the best option for Uyghur women in Xinjiang in a previous study. In this research, we aim to discuss the appropriate age for Uyghur women in Xinjiang to be screened for cervical cancer using careHPV. Methods Eleven thousand women aged 20–69 years old (mean age 38.93 ± 9.74) from South Xinjiang were screened using careHPV and liquid‐based cytology, and the positive results were referred for colposcopy and cervical biopsy. A questionnaire regarding basic social characteristics, sexual practices, and reproductive history was administered to each woman. The age‐specific prevalence of HPV positivity, cytology abnormality, and cervical intraepithelial neoplasia (CIN) 2+ in ≥25, ≥30, and ≥35 age groups were analyzed, and the diagnostic value of careHPV in the three age groups was evaluated. The chi‐squared test was used to compare the differences between age groups. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve were calculated. Results The women were mostly married (76.3%) and delivered at 15–19 years of age (61.4%). The HPV infection rate was 9.15% and detection rates of CIN2+ and invasive cervical cancer were 1.53% (1530/100,000) and 0.25% (250/100,000), respectively. The first peak of HPV(+) appeared at the age of 30–34, while CIN2+ appeared at 35–39. CareHPV performed similarly well in the three age groups. Conclusion Based on the results of our study, Uyghur women in Xinjiang should be recommended to initiate cervical cancer screening at the age of 30 years when screened using careHPV.

Abstract Recently, a new type of subsynchronous oscillation (SSO) has occurred in doubly‐fed induction generator (DFIG)‐based wind farms. This oscillation is also called the subsynchronous control interaction (SSCI), which is mainly caused by the interaction between the transmission series compensation and the DFIG controller. Therefore, the oscillation frequency of the SSCI is susceptibly impacted by DFIG operating conditions, which presents major challenges to conventional mitigation strategies. To solve this problem, a grid‐connected series‐compensated DFIG‐based wind farm is established, and the formation process of the SSCI is analysed. The strategy of active disturbance rejection control (ADRC), which can automatically estimate and compensate for the total disturbance of the system in real‐time, is introduced into the rotor‐side converter to mitigate the SSCI in the DFIG. ADRC is designed based on dynamic parameter tuning and chaos optimization. Finally, a detailed model‐based time‐domain simulation is conducted to evaluate the performance of the proposed optimized ADRC (O‐ADRC) compared to conventional virtual impedance and ADRC. The simulation results show that O‐ADRC can effectively mitigate the SSCI under different operating conditions and provide sufficient damping for the DFIG‐based wind farms.

Abstract Background It has been well documented that social isolation stress (SIS) can induce posttraumatic stress disorder (PTSD)‐like behavior in rodents, however, the underlying mechanism is remained misunderstood. In the current study, we aimed to elucidate the role of NO/NMDAR pathway in PTSD‐like behavior through modulating of astrocyte activity and improvement of oxidative stress. Methods Male NMRI mice were used to evaluate the memory function by using Morris water maze (MWM) and fear memory extinction by using freezing response. We used MK‐801 (NMDAR‐antagonist), L‐NNA (NOS‐inhibitor), NMDA (NMDAR‐agonist), and L‐arginine (NO‐agent) to find a proper treatment. Also, immunohistochemistry, RT‐PCR, and oxidative stress assays were used to evaluate the levels of astrocytes and oxidative stress. We used five mice in each experimental task. Results Our results revealed that SIS could induce learning and memory dysfunction as well as impairment of fear memory extinction in MWM and freezing response tests, respectively. Also, we observed that combined treatment including blockage of NOS (by L‐NNA, 0.5 mg/kg) and NMDAR (by MK‐801, 0.001 mg/kg) at subeffective doses could result in improvement of both memory and fear memory. In addition, we observed that SIS significantly increases the GFAP expression and astrocyte activity, which results in significant imbalance in oxidative stress. Coadministration of MK‐801 and L‐NNA at subeffective doses not only decreases the expression of GFAP, but also regulates the oxidative stress imbalance Conclusion Based on these results, it could be hypothesized that blockage of NO/NMDAR pathway might be a novel treatment for PTSD‐like behavior in animals by inhibiting the astrocyte and regulating oxidative stress level.

Abstract Objective Buccal cells are an ideal surrogate tissue for studying biologic effects of carcinogens or drugs, however inherent fragility and salivary RNAses limit RNA yield. We conducted healthy volunteer trials to optimize collection conditions. Methods We conducted: (a) a single‐arm crossover study evaluating four test conditions on RNA yield by buccal cytobrush; (b) a single‐arm prospective study evaluating RNA yield by investigator vs self‐collection. Results Antecedent toothbrushing, time of day, and number of cytobrush strokes did not significantly impact RNA yield. RNA yield was doubled by using 2 vs 1 cytobrush per buccal surface (P = .0054). Self‐collection of buccal cells for RNA was feasible; 36 of 50 (72%) samples passed quality control. Conclusion RNA yield was doubled by using two cytobrushes per buccal surface. Healthy volunteers can self‐collect sufficient buccal RNA for gene expression studies. Techniques from these pragmatic trials could enhance availability of a limited tissue for serial biomarker measurements. Level of Evidence 1b—Prognosis Study (Individual prospective cohort study).

Abstract Breast cancer is the second deadliest cancer among women. Mammography is an important method for physicians to diagnose breast cancer. The main purpose of this study is to use deep learning to automatically classify breast masses in mammograms into benign and malignant. This study proposes a two‐view mammograms classification model consisting of convolutional neural network (CNN) and recurrent neural network (RNN), which is used to classify benign and malignant breast masses. The model is composed of two branch networks, and two modified ResNet are used to extract breast‐mass features of mammograms from craniocaudal (CC) view and mediolateral oblique (MLO) view, respectively. In order to effectively utilise the spatial relationship of the two‐view mammograms, gate recurrent unit (GRU) structures of RNN is used to fuse the features of the breast mass from the two‐view. The digital database for screening mammography (DDSM) be used for training and testing our model. The experimental results show that the classification accuracy, recall and area under curve (AUC) of our method reach 0.947, 0.941 and 0.968, respectively. Compared with previous studies, our method has significantly improved the performance of benign and malignant classification.

Osteoporosis and osteoarthritis are orthopedic disorders that affect millions of elderly people worldwide; stimulation of bone formation is a potential therapeutic strategy for the treatment of these conditions. As the only bone‐forming cells, osteoblasts play a key role in bone reconstruction. The microRNA miR‐17‐3p is downregulated during osteogenic differentiation of human bone marrow mesenchymal stem cells, but its precise role in this process is unknown. Here, we investigated the role of miR‐17‐3p in osteoblast differentiation. An in vitro model of osteogenesis was established by treating MC3T3‐E1 murine preosteoblast cells with bone morphogenetic protein 2 (BMP2). The expression of miR‐17‐3p in BMP2‐induced MC3T3‐E1 cells was detected by reverse transcription‐quantitative PCR, and its effects on cells transfected with miR‐17‐3p mimic or inhibitor were evaluated by Alizarin Red staining, alkaline phosphatase (ALP) activity assay, and by detection of osteoblast markers including the ALP, collagen type I α1 chain, and osteopontin genes. Bioinformatics analysis was carried out to identify putative target genes of miR‐17‐3p, and the luciferase reporter assay was used for functional validation. Rescue experiments were performed to determine whether SRY‐box transcription factor 6 (Sox6) plays a role in the regulation of osteoblast differentiation by miR‐17‐3p. We report that miR‐17‐3p was downregulated upon BMP2‐induced osteoblast differentiation in MC3T3‐E1 cells, and this was accompanied by decreased differentiation and mineralization, ALP activity, and expression of osteogenesis‐related genes. Sox6 was confirmed to be a target gene of miR‐17‐3p in osteoblasts, and the inhibitory effect of miR‐17‐3p on osteoblast differentiation was observed to occur via Sox6. These results suggest the existence of a novel mechanism underlying miRNA‐mediated regulation of osteogenesis, which has potential implications for the treatment of orthopedic disorders.

Abstract With the rapid development of data‐driven human interaction, advanced data‐storage technologies with lower power consumption, larger storage capacity, faster switching speed, and higher integration density have become the goals of future memory electronics. Nevertheless, the physical limitations of conventional Si‐based binary storage systems lag far behind the ultrahigh‐density requirements of post‐Moore information storage. In this regard, the pursuit of alternatives and/or supplements to the existing storage technology has come to the forefront. Recently, organic‐based resistive memory materials have emerged as promising candidates for next‐generation information storage applications, which provide new possibilities of realizing high‐performance organic electronics. Herein, the memory device structure, switching types, mechanisms, and recent advances in organic resistive memory materials are reviewed. In particular, their potential of fulfilling multilevel storage is summarized. Besides, the present challenges and future prospects confronted by organic resistive memory materials and devices are discussed.

Abstract Background Adequate cytology is limited by insufficient cytologists in a large‐scale cervical cancer screening. We aimed to develop an artificial intelligence (AI)‐assisted cytology system in cervical cancer screening program. Methods We conducted a perspective cohort study within a population‐based cervical cancer screening program for 0.7 million women, using a validated AI‐assisted cytology system. For comparison, cytologists examined all slides classified by AI as abnormal and a randomly selected 10% of normal slides. Each woman with slides classified as abnormal by either AI‐assisted or manual reading was diagnosed by colposcopy and biopsy. The outcomes were histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results Finally, we recruited 703 103 women, of whom 98 549 were independently screened by AI and manual reading. The overall agreement rate between AI and manual reading was 94.7% (95% confidential interval [CI], 94.5%‐94.8%), and kappa was 0.92 (0.91‐0.92). The detection rates of CIN2+ increased with the severity of cytology abnormality performed by both AI and manual reading (Ptrend

Abstract Memristors are a new type of circuit element with a resistance that is tunable to discrete levels by a voltage/current and sustainable after removal of power, allowing for low‐power computation and multilevel information storage. Many organic‐inorganic lead perovskites are reported to demonstrate memristive behavior, but few have been considered for use as a multilevel memory; also, their potential application has been hindered by the toxicity of lead ions. In this article, lead‐free perovskite MASnBr3 was utilized in memristors for quaternary information storage. Indium tin oxide (ITO)/MASnBr3/Au memristors were fabricated and showed reliable memristive switching with well‐separated ON/OFF states of a maxima resistance ratio of 102 to 103. More importantly, four resistive states can be distinguished and repeatedly written/read/erased with a retention time of 104 seconds and an endurance of 104 pulses. By investigating the current‐electrode area relationship, Br distribution in the ON/OFF states by in situ Raman and scanning electron microscopy, and temperature‐dependent current decay, the memristive behavior was explicitly attributed to the forming/breaking of conductive filaments caused by the migration of Br− under an electric field. In addition, poly(ethylene terephthalate)‐ITO/MASnBr3/Au devices were found to retain their multiresistance state behavior after being bent for 1000 times, thus demonstrating good device flexibility. Our results will inspire more lead‐free perovskite work for multilevel information storage, as well as other memristor‐based electronics.

Abstract Background CCL22 played critical roles in Tregs recruitment. The upstream regulators modulating CCL22 in hepatocellular carcinoma (HCC) were not clearly understood. Methods MiR‐23a, p‐p65, p65, CCL22, and Foxp3 levels were monitored by RT‐qPCR and western blotting. Immunofluorescence assay was used to perform the costaining of Foxp3 and CD4 on liver tissues. Transwell assay was applied to evaluate the migration ability of Tregs. Dual‐luciferase assay was performed to determine relationship of miR‐23a/CCL22 and p65/miR‐23a. Chromatin immunoprecipitation (ChIP) was applied to detect the direct binding of p65 to miR‐23a promoter. Xenograft tumor models were developed to investigate the functions of p65 and miR‐23a in vivo. Results HBV infection was associated with reduced survival and increased Tregs recruitment in HCC patients. MiR‐23a was decreased, whereas p65, CCL22, and Foxp3 were increased in HBV+ tumors. MiR‐23a was inversely correlated with CCL22 and Foxp3 expression in HCC. MiR‐23a directly targeted CCL22 3’UTR, leading to CCL22 reduction and attenuated Tregs recruitment. Meanwhile, p65 functioned as a transcription repressor of miR‐23a by directly binding to its promoter. Inhibition of p65 induced miR‐23 expression, leading to less CCL22 expression and Tregs recruitment in vitro. CCL22 was the indispensable effector underlying p65/miR‐23a axis and Tregs recruitment. MiR‐23a inhibitor promoted xenografted tumor growth accompanying with upregulation of CCL22, whereas p65 inhibition exerted opposite effects. Conclusion Blockage of p65 disinhibited miR‐23a expression, leading to CCL22 reduction and repress Tregs recruitment. Targeting p65/miR‐23a/CCL22 axis was a novel approach for HBV+ HCC treatment.

Background. Colon cancer is a common gastrointestinal malignancy. It has been discovered that Farnesoid X receptor (FXR) plays an imperative regulatory role in multitype cancers in recent years. However, its regulatory mechanism in colon cancer has not been clearly explored. This study intended to explore the molecular regulatory mechanism of FXR and its downstream genes on the malignant progression of colon cancer. Methods. The mRNA and protein expression of FXR in colon cancer cells were measured by quantitative real-time polymerase chain reaction and Western blot. The effects of FXR on the biological function of colon cancer cells were measured by Cell Counting Kit-8, colony formation, and transwell assays. The downstream target gene of FXR was predicted by bioinformatics analysis and found to be associated with cellular oxidative phosphorylation. The binding relationship between FXR and its downstream gene dehydrogenase/reductase member 9 (DHRS9) was verified through luciferase reporter assay and chromatin immunoprecipitation assay. The changes of oxidative phosphorylation were detected by Western blot and oxygen consumption rate determination. The effect of FXR/DHRS9 axis on the malignant progression of colon cancer cells was further confirmed by rescue experiments. Results. FXR was underexpressed in colon cancer tissues and cells, and overexpressing FXR could repress the malignant behaviors of colon cancer cells. Besides, DHRS9 was a downstream gene of FXR, and FXR/DHRS9 inhibited the deterioration of colon cancer through inhibiting oxidative phosphorylation. Moreover, promoting FXR expression in colon cancer cells could partially reverse the biological function changes caused by silencing DHRS9 expression. Conclusion. FXR inhibited the oxidative phosphorylation and inhibited the malignant progression of colon cancer cells via targeting DHRS9.

Abstract Cardiac voltage‐gated ion channels (VGICs) play critical roles in mediating cardiac electrophysiological signals, such as action potentials, to maintain normal heart excitability and contraction. Inherited or acquired alterations in the structure, expression, or function of VGICs, as well as VGIC‐related side effects of pharmaceutical drug delivery can result in abnormal cellular electrophysiological processes that induce life‐threatening cardiac arrhythmias or even sudden cardiac death. Hence, to reduce possible heart‐related risks, VGICs must be acknowledged as important targets in drug discovery and safety studies related to cardiac disease. In this review, we first summarize the development and application of electrophysiological techniques that are employed in cardiac VGIC studies alone or in combination with other techniques such as cryoelectron microscopy, optical imaging and optogenetics. Subsequently, we describe the characteristics, structure, mechanisms, and functions of various well‐studied VGICs in ventricular myocytes and analyze their roles in and contributions to both physiological cardiac excitability and inherited cardiac diseases. Finally, we address the implications of the structure and function of ventricular VGICs for drug safety evaluation. In summary, multidisciplinary studies on VGICs help researchers discover potential targets of VGICs and novel VGICs in heart, enrich their knowledge of the properties and functions, determine the operation mechanisms of pathological VGICs, and introduce groundbreaking trends in drug therapy strategies, and drug safety evaluation.

Abstract Background Several ECG criteria have been widely used for diagnosis of left ventricular hypertrophy (LVH) in clinical practice. However, their performance in a general Chinese population is limited. Methods and results A multi‐stage, stratified cluster sampling across China was performed and 7415 representative Chinese adults aged 18–85 years were analyzed. ECG was collected by using GE MAC 5500 machine. The association between five ECG‐LVH criteria (i.e., Peguero–Lo Presti, Cornell, Cornell product, Sokolow–Lyon and Sokolow–Lyon product) and echocardiographic LVH (Echo‐LVH) was assessed by Pearson's correlation, diagnostic statistics like predictive values, and receiver operating characteristics (ROC) curve. We found that the prevalence of the Echo‐LVH was 11% while ECG‐LVH ranged from 3% to 27%. All ECG‐LVH criteria had high negative predictive value (NPV) (89%) and specificity (73–96%) but low positive predictive value (PPV) (12–24%) and sensitivity (4–29%). The newly Peguero–Lo Presti criteria had higher sensitivity (29%) but lower specificity (73%) and accuracy (68%) compared with other criteria. Cornell product had the best diagnostic performance (AUC: 0.59), as well as the highest specificity (96%) and accuracy (86%) but lowest sensitivity (4%). Among single‐lead components of ECG criteria, RaVL voltage and QRS duration performed relatively better than others. Hypertensive and older individuals had higher sensitivity but lower specificity and accuracy than their counterparts. Conclusion ECG‐LVH criteria had high NPV to detect Echo‐LVH. Though with higher sensitivity, Peguero–Lo Presti criteria did not have better diagnostic performance to detect Echo‐LVH. RaVL and QRS duration had stronger association with Echo‐LVH among all single‐lead components.

Abstract Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment‐naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC‐related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top‐ranked prognostic proteins X‐prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well‐known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi‐omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC.

Abstract Objectives Lamotrigine is used to treat bipolar depression despite inconsistent evidence. Here we present the results of an exploratory item‐level analysis of pooled data from five randomized placebo‐controlled trials of lamotrigine for acute bipolar depression. The goal was to determine if certain depression scale items were more responsive to lamotrigine treatment. Methods The pooled sample contained 1072 adult outpatients treated for up to 7–10 weeks. Depressive symptoms were measured with the Hamilton Depression Rating Scale and the Montgomery–Åsberg Depression Rating Scale. Change scores on individual scale items were compared between treatment groups. Results There were statistically significant effects on items assessing depressed mood/sadness, lack of interest/anhedonia, pessimism/guilt, and anergia/fatigue, on both scales. However, there was marked variation in the baseline symptom prevalence, and items with higher scores at baseline tended to have larger and statistically significant treatment effects. Conclusions The results suggested a significant treatment effect on core symptoms of depression. A floor effect appeared to limit the sensitivity of other scale items. Given the exploratory nature of the analysis, firm conclusions cannot be drawn, although the results were consistent with past research. Relying on total depression scale sum scores over targeted assessments of core depressive symptoms may have impeded signal detection in the original trials.

Abstract Background Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. Prenatal screening of FXS allows for early identification and intervention. The present study explored the feasibility of FXS carrier screening during prenatal diagnosis for those who were not offered screening early in pregnancy or prior to conception. Methods Pregnant women to be offered amniotic fluid testing were recruited for the free voluntary carrier screening at a single center between August, 2017 and September, 2019. The number of CGG repeats in the 5’ un‐translated region of the fragile X mental retardation gene 1 (FMR1) was determined. Results 4286 of 7000 (61.2%) pregnant women volunteered for the screening. Forty (0.93%), five (0.11%), and three (0.07%) carriers for intermediate mutation (45–54 repeats), premutation (55–200 repeats) and full mutation (>200 repeats) of the FMR1 gene were identified respectively. None of the detected premutation alleles were inherited by the fetuses. Of the three full mutation carrier mothers, all had a family history and one transmitted a full mutation allele to her male fetus. Conclusion Implementation of FXS carrier screening during prenatal diagnosis may be considered for the need to increase screening for FXS.

Abstract Objects The diffusion‐based spherical mean technique (SMT) provides a novel model to relate multi‐b‐value diffusion magnetic resonance imaging (MRI) data to features of tissue microstructure. We propose the first clinical application of SMT to image the brain of patients with multiple sclerosis (MS) and investigate clinical feasibility and translation. Methods Eighteen MS patients and nine age‐ and sex‐matched healthy controls (HCs) underwent a 3.0 Tesla scan inclusive of clinical sequences and SMT images (isotropic resolution of 2 mm). Axial diffusivity (AD), apparent axonal volume fraction (Vax), and effective neural diffusivity (Dax) parametric maps were fitted. Differences in AD, Vax, and Dax between anatomically matched regions reflecting different tissues types were estimated using generalized linear mixed models for binary outcomes. Results Differences were seen in all SMT‐derived parameters between chronic black holes (cBHs) and T2‐lesions (P ≤ 0.0016), in Vax and AD between T2‐lesions and normal appearing white matter (NAWM) (P

Abstract The ban on the use of antibiotic in feed encouraged nutritionists to using alternatives to maintain growth performance and intestinal function of broilers. This study was conducted to evaluate the effects of Yupingfeng polysaccharides (YP) supplementation on growth performance and expression of SGLT1, GLUT2 and GLUT5 in Qingyuan partridge chicken. Experiment 1: a total of 540 chickens were randomly allocated to five groups with six replication. Dietary treatments were: (1) CON (control group), basal diet; (2) T1, CON + 0.5 g kg−1 YP; (3) T2, CON + 1 g kg−1 YP; (4) T3, CON + 2 g kg−1 YP; (5) T4, CON + 4 g kg−1 YP. Experiment 2, a total of 162 were randomly allocated to three groups with three replication. Dietary treatments were: (1) CON, basal diet; (2) T1, CON + 0.5 g kg−1 YP; (3) T2, CON + 1 g kg−1 YP. From days 1 to 14 and overall, chicken fed T1 diet had higher ADG. On day 42, there was increased villus height of jejunum in T1 group. On days 14 and 28, there was decreased villus height of duodenum and jejunum in T2 group. In duodenum, the expression of SGLT1 (days 21, 35 and 42), GLUT2 (days 7, 14, 21, 28, 35 and 42) and GLUT5 (days 7, 14, 21 and 28) was increased with YP supplementation. In jejunum, the expression of SGLT1 (days 7, 14, 21, 28 and 35), GLUT2 (days 14, 21, 28, 35 and 42) and GLUT5 (days 7, 14, 21, 28, 35 and 42) was increased with YP supplementation. In ileum, the expression of SGLT1 (days 7, 21, 35 and 42), GLUT2 (days 7, 14, 21 and 42) and GLUT5 (days 7, 14, 21, 28, 35 and 42) was increased with YP supplementation. Dietary YP supplementation improves growth performance and expression of SGLT1, GLUT2 and GLUT5 in intestine.

Abstract Background Surfactant protein D (SP‐D) is an innate immunity molecule in the alveoli. However, the associations between genetic variants of SP‐D and radiation pneumonitis (RP) have never been investigated. Methods The Linkage disequilibrium of SP‐D and tagSNPs were analyzed by using Haploview 4.1. Eight tagSNPs were genotyped among 396 lung cancer patients who received thoracic radiation therapy with follow–up time (median [P25, P75]: 11[6, 18]) using improved multiplex ligation detection reaction (iMLDR). The associations between clinical characteristics, tagSNP alleles, genotypes, haplotypes and onset time of grade ≥2 or ≥3 RP were evaluated by using univariate and multivariate Cox proportional hazard regression model. Results Three tagSNPs of SP‐D (rs1998374, rs911887 and rs2255326) were significantly associated with grade ≥2 RP in multivariate analysis with multiple testing (Q test). The rs199874 had a protective effect for grade ≥2 RP in the dominant model (Hazard ratio (HR), 0.575; 95% confidence interval (CI), 0.378‐0.875). The homozygous mutant genotype for rs911887 had risk effect for grade ≥2 RP (HR, 2.209; 95% CI, 1.251‐3.902). The A mutant allele of rs2255326 also showed an elevated risk for grade ≥2 RP (HR, 1.777; 95% CI, 1.283‐2.461) and this risk effect was still significant in the recessive genetic model (HR, 3.320; 95% CI, 1.659‐6.644) and dominant genetic model (HR, 1.773; 95% CI, 1.166‐2.696). Compared to the lung cancer patients bearing the most common haplotype C‐G‐T, the patients bearing the haplotype T‐A‐C (rs1998374‐rs2255326‐rs911887) showed a significant risk of both grade ≥2 RP (HR, 1.885; 95% CI, 1.284‐2.765) and grade ≥3 RP (HR, 2.256; 95% CI, 1.248‐4.080). Conclusions Genetic variants of SP‐D were associated with risk of RP development in lung cancer patients receiving thoracic radiotherapy.

Abstract Background Mesenchymal stem cells (MSCs) have therapeutic potential for multiple ischemic diseases. However, in vitro expansion of MSCs before clinical application leads to metabolic reprogramming from glycolysis to oxidative phosphorylation, drastically impairing their proliferative and therapeutic capacities. This study aimed to define the regulatory effects of Sirtuin 5 (SIRT5) on the proliferative and therapeutic functions of adipose‐derived MSCs (ADMSCs) during in vitro expansion. Methods ADMSCs were isolated from wild‐type (WT) and Sirt5‐knockout (Sirt5−/−) mice. Cell counting assay was used to investigate the proliferative capacities of the ADMSCs. Dihydroethidium and senescence‐associated β‐galactosidase stainings were used to measure intracellular ROS and senescence levels. Mass spectrometry was used to analyze protein succinylation. Oxygen consumption rates and extra cellular acidification rates were measured as indicators of mitochondrial respiration and glycolysis. Metabolic‐related genes expression were verified by quantitative PCR and western blot. Hind limb ischemia mouse model was used to evaluate the therapeutic potentials of WT and Sirt5−/− ADSMCs. Results SIRT5 protein levels were upregulated in ADMCs during in vitro expansion. Sirt5−/− ADMSCs exhibited a higher proliferation rate, delayed senescence, and reduced ROS accumulation. Furthermore, elevated protein succinylation levels were observed in Sirt5−/− ADMSCs, leading to the reduced activity of tricarboxylic acid cycle‐related enzymes and attenuated mitochondrial respiration. Glucose uptake, glycolysis, and pentose phosphate pathway were elevated in Sirt5−/− ADMSCs. Inhibition of succinylation by glycine or re‐expression of Sirt5 reversed the metabolic alterations in Sirt5−/‐ ADMSCs, thus abolishing their enhanced proliferative capacities. In the hind limb ischemia mouse model, SIRT5−/− ADMSCs transplantation enhanced blood flow recovery and angiogenesis compared with WT ADMSCs. Conclusions Our results indicate that SIRT5 deficiency during ADMSC culture expansion leads to reversed metabolic pattern, enhanced proliferative capacities, and improved therapeutic outcomes. These data suggest SIRT5 as a potential target to enhance the functional properties of MSCs for clinical application.

Abstract The pandemic of novel coronavirus disease 2019 (COVID‐19) seriously threatened the public health all over the world. A colloidal gold immunochromatography assay for IgM/IgG antibodies against the receptor‐binding domain of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) S1 protein was established to assess its rapid diagnostic value. We first designed and manufactured all contents of the test cassette of SARS‐CoV‐2 rapid test kit: the colloidal gold‐labeled mouse‐antihuman lgM/lgG antibody, the recombinant SARS‐CoV‐2 antigen, the nitrocellulose membrane control line, and specimen diluents. Furthermore, reverse transcription‐polymerase chain reaction (RT‐PCR) assay, colloidal gold immunochromatography assay, serological validation of cross reaction with other common viruses, and clinical validation were performed. The kit was finally evaluated by 75 serum/plasma samples of SARS‐CoV‐2 infection cases and 139 healthy samples as control, with the result of that the sensitivity, specificity, and accuracy for IgM were 90.67%, 97.84%, and 95.33%, whereas for IgG were 69.33%, 99.28%, and 88.79%, respectively; the combination of IgM and IgG could improve the value: 92.00%, 97.12%, and 95.33%, respectively. Therefore, the rapid detection kit has high sensitivity and specificity, especially for IgM&IgG, showing a critical value in clinical application and epidemic control of COVID‐19.

Abstract A strategy for efficaciously regulating perovskite crystallinity is proposed by using a volatile solid glycolic acid (HOCH2COOH, GA) in an FA0.85MA0.15PbI3 (FA: HC(NH2)2; MA: CH3NH3) perovskite precursor solution that is different from the common additive approach. Accompanied with the first dimethyl sulfoxide sublimation process, the subsequent sublimation of GA before 150 °C in the FA0.85MA0.15PbI3 perovskite film can artfully regulate the perovskite crystallinity without any residual after annealing. The improved film formation upon GA modification induced by the strong interaction between GA and Pb2+ delivers a champion power conversion efficiency (PCE) as high as 21.32%. In order to investigate the role of volatility in perovskite solar cells (PSCs), nonvolatile thioglycolic acid (HSCH2COOH, TGA) with a similar structure to GA is utilized as an additive reference. Large perovskite grains are obtained by TGA modification but with obvious pinholes, which directly leads to an increased defect density accompanied by a decline in PCE. Encouragingly, the champion PCE achieved for GA‐based PSC device (21.32%) is almost 13% or 20% higher than those of the control device or TGA‐based device. In addition, GA‐modified PSCs exhibit the best stability in light‐, thermal‐, and humidity‐based tests due to the improved film formation.

Abstract Anlotinib is a multitargeted antiangiogenic drug, and its clinical predictor for responsive non‐small cell lung cancer (NSCLC) patients is still elusive. Here, tumor‐specific target capture is used to profile the circulating DNA of ALTER0303 (evaluating NSCLC clinical antitumor efficacy through anlotinib therapy) study participants. The results indicate that patients receiving no benefit can be mainly excluded via analysis of ARID1A and BRCA2 genetic profiling. For patients with no durable benefit and durable clinical benefit patients, three predictors: germline and somatic mutation burden (G+S MB), nonsynonymous and synonymous mutation burden (N+S MB), and unfavorable mutation score of circulating DNA profiling are identified. Through integrating the advantages and disadvantages of three independent predictors, the tumor mutation index (TMI) is established as a prediction model and the patients who are very likely to benefit more from anlotinib therapy are identified. Furthermore, the IDH1exon 4 mutation is identified as an unfavorable factor for anlotinib therapy under TMI‐based stratification, and the TMI plus IDH1exon 4 mutation status potentially predicts response to anlotinib. Collectively, this study provides a circulating DNA sequencing–based stratification method for identifying anlotinib responders via a noninvasive approach, and thus potentially improves the clinical outcome of NSCLC patients receiving third‐line therapy.

Abstract Optical frequency combs, consisting of well‐controlled equidistant frequency lines, have been widely used in precision spectroscopy and metrology. Terahertz combs have been realized in quantum cascade lasers (QCLs) by employing either an active mode‐locking or phase seeding technique, or a dispersion compensator mirror. However, it remains a challenge to achieve the passive comb formation in terahertz semiconductor lasers due to the insufficient nonlinearities of conventional saturable absorbers. Here, a passive terahertz frequency comb is demonstrated by coupling a multilayer graphene sample into a QCL compound cavity. The terahertz modes are self‐stabilized with intermode beat note linewidths down to a record of 700 Hz and the comb operation of graphene‐coupled QCLs is validated by on‐chip dual‐comb measurements. Furthermore, the optical pulse emitted from the graphene‐coupled QCL is directly measured employing a terahertz pump–probe technique. The enhanced passive frequency comb operation is attributed to the saturable absorption behavior of the graphene‐integrated saturable absorber mirror, as well as the dispersion compensation introduced by the graphene sample. The results provide a conceptually different graphene‐based approach for passive comb formation in terahertz QCLs, opening up intriguing opportunities for fast and high‐precision terahertz spectroscopy and nonlinear photonics.

The overall technology of passive radar and application overview in civil aviation are reviewed here, and the research history and status in this field are introduced. It is pointed out that the passive radar has huge application prospects in general aviation surveillance and drone surveillance of the airport terminal area. Then, the key technologies including system synchronisation, reference signal acquisition, weak target signal detection, and single-frequency network defuzzification are analysed. Finally, the development trends of passive radar are proposed to integrate into existing air traffic management systems, multi-band integration, and system networking, which indicates the research direction of this new radar system in civil aviation application.

Abstract A high‐quality perovskite photoactive layer plays a crucial role in determining the device performance. An additive engineering strategy is introduced by utilizing different concentrations of N,1‐diiodoformamidine (DIFA) in the perovskite precursor solution to essentially achieve high‐quality monolayer‐like perovskite films with enhanced crystallinity, hydrophobic property, smooth surface, and grain size up to nearly 3 µm, leading to significantly reduced grain boundaries, trap densities, and thus diminished hysteresis in the resultant perovskite solar cells (PSCs). The optimized devices with 2% DIFA additive show the best device performance with a significantly enhanced power conversion efficiency (PCE) of 21.22%, as compared to the control devices with the highest PCE of 19.07%. 2% DIFA modified devices show better stability than the control ones. Overall, the introduction of DIFA additive is demonstrated to be a facile approach to obtain high‐efficiency, hysteresis‐less, and simultaneously stable PSCs.

Objective. To investigate the relationship between hemoglobin levels and diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM). Methods. 1511 patients with T2DM were included in the study. DPN was diagnosed based on symptoms, signs, and laboratory tests. Hemoglobin was defined as both a continuous variable and a quartile category variable. We compared patient characteristics between the no diabetic peripheral neuropathy (NDPN) and DPN groups. Logistic regression was conducted to investigate the association of DPN with hemoglobin in all T2DM patients. Linear regression was also performed to investigate the impact of hemoglobin on the vibrating perception threshold (VPT). Results. Compared with the NDPN group, hemoglobin level in the DPN group was significantly lower (118.54 ± 16.91 versus 131.62 ± 18.32 g/L, P

The Effective Heat Source (EHS) and Effective Momentum Source (EMS) models have been proposed to predict the development of thermal stratification and mixing during a steam injection into a large pool of water. These effective models are implemented in GOTHIC software and validated against the POOLEX STB-20 and STB-21 tests and the PPOOLEX MIX-01 test. First, the EHS model is validated against STB-20 test which shows the development of thermal stratification. Different numerical schemes and grid resolutions have been tested. A 48×114 grid with second order scheme is sufficient to capture the vertical temperature distribution in the pool. Next, the EHS and EMS models are validated against STB-21 test. Effective momentum is estimated based on the water level oscillations in the blowdown pipe. An effective momentum selected within the experimental measurement uncertainty can reproduce the mixing details. Finally, the EHS-EMS models are validated against MIX-01 test which has improved space and time resolution of temperature measurements inside the blowdown pipe. Excellent agreement in averaged pool temperature and water level in the pool between the experiment and simulation has been achieved. The development of thermal stratification in the pool is also well captured in the simulation as well as the thermal behavior of the pool during the mixing phase.

Owing to the high dimensionality of multilabel data, feature selection in multilabel learning will be necessary in order to reduce the redundant features and improve the performance of multilabel classification. Rough set theory, as a valid mathematical tool for data analysis, has been widely applied to feature selection (also called attribute reduction). In this study, we propose a variable precision attribute reduct for multilabel data based on rough set theory, called δ-confidence reduct, which can correctly capture the uncertainty implied among labels. Furthermore, judgement theory and discernibility matrix associated with δ-confidence reduct are also introduced, from which we can obtain the approach to knowledge reduction in multilabel decision tables.