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Abstract Although the association between persistent hypertension and the compromise of both micro‐ and macro‐circulatory functions is well recognized, a significant gap in quantitative investigations exploring the interplay between microvascular and macrovascular injuries still exists. In this study, the authors looked into the relationship between brachial‐ankle pulse wave velocity (baPWV) and hypertensive retinopathy in treated hypertensive adults. The authors conducted a cross‐sectional study of treated hypertensive patients with the last follow‐up data from the China Stoke Primary Prevention Trial (CSPPT) in 2013. With the use of PWV/ABI instruments, baPWV was automatically measured. The Keith‐Wagener‐Barker classification was used to determine the diagnosis of hypertensive retinopathy. The odds ratio (OR) and 95% confidence interval (CI) for the connection between baPWV and hypertensive retinopathy were determined using multivariable logistic regression models. The OR curves were created using a multivariable‐adjusted restricted cubic spline model to investigate any potential non‐linear dose‐response relationships between baPWV and hypertensive retinopathy. A total of 8514 (75.5%) of 11,279 participants were diagnosed with hypertensive retinopathy. The prevalence of hypertensive retinopathy increased from the bottom quartile of baPWV to the top quartile: quartile 1: 70.7%, quartile 2: 76.1%, quartile 3: 76.7%, quartile 4: 78.4%. After adjusting for potential confounders, baPWV was positively associated with hypertensive retinopathy (OR = 1.05, 95% CI, 1.03–1.07, p

ABSTRACT Background Early on in the development of diabetes, skeletal muscles can exhibit microarchitectural changes that can be detected using texture analysis (TA) based on volume transfer constant (Ktrans) maps. Nevertheless, there have been few studies and thus we evaluated microvascular permeability and the TA of the bone marrow in diabetics with critical limb ischemia (CLI). Methods Eighteen male rabbits were randomly assigned equally into an operation group with hindlimb ischemia and diabetes, a sham‐operated group with diabetes only, and a control group. Dynamic contrast enhanced magnetic resonance imaging (DCE‐MRI) was performed on all rabbits at predetermined intervals (1, 5, 10, 15, 20, and 25 days post‐surgery). The pharmacokinetic model was used to generate the permeability parameters, while the textural parameters were derived from the Ktrans map. Data analysis methods included the independent sample t‐test, Mann–Whitney U test, repeated‐measures analysis of variance, and Pearson correlation tests. Results The Ktrans values reached a minimum on day 1 after ischemia induction, then gradually recovered, but remained lower than those of the sham‐operated group. The volume fraction only showed a significant difference between the operation group and the sham‐operated group on day 5 post‐surgery, but not in the extravascular extracellular space volume fraction at all time points. A significantly reduced Ktrans on day 1, a decreased number of bone trabeculae (Tb.N), and the area of bone trabeculae (Tb.Ar), and an increased microvessel density on day 25 in the operation group compared with the sham‐operated group were observed. At each time point, there was a discernible difference between the two groups in the mean value, mean of positive pixels, and sumAverage. Conclusions The early stages of diabetic bone marrow with CLI can be evaluated by DCE‐MRI for microvascular permeability. Texture analysis based on DCE‐MRI could act as an imaging discriminator and new radiological analysis tool for critical limb ischemia in diabetes mellitus.

Abstract Lack of liver regenerative capacity is the primary cause of hepatic failure and even mortality in patients undergoing hepatectomy, with no effective intervention strategies currently available. Therefore, identifying efficacious interventions to enhance liver regeneration is pivotal for optimizing clinical outcomes. Recent studies have demonstrated that vagotomy exerts an inhibitory effect on liver regeneration following partial hepatectomy, thereby substantiating the pivotal role played by the vagus nerve in the process of liver regeneration. In recent years, electroacupuncture (EA) has emerged as a non‐invasive technique for stimulating the vagus nerve. However, EA on hepatic regeneration remains uncertain. In this study, a 70% partial hepatectomy (PH) mouse model is utilized to investigate the effects of EA on acute liver regeneration and elucidate its underlying molecular mechanisms. It is observed that EA at ST36 acutely activated cholinergic neurons in the dorsal motor nucleus of the vagus nerve (DMV), resulting in increased release of acetylcholine from hepatic vagal nerve endings and subsequent activation of IL‐6 signaling in liver macrophages. Ultimately, these events promoted hepatocyte proliferation and facilitated liver regeneration. These findings provide insights into the fundamental brain‐liver axis mechanism through which EA promotes liver regeneration, offering a novel therapeutic approach for post‐hepatectomy liver regeneration disorders.

Abstract Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1‐DXd) is elucidated. DAC treatment significantly enhanced anti‐tumor efficacy of I1‐DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1‐DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.

Abstract N‐glycosylation has important implications for the physicochemical properties and biochemical activity of breast milk proteins. However, an in‐depth characterization of site‐specific N‐glycans in breast milk serum proteins is lacking. In this study, 875 site‐specific N‐glycans attached to 114 serum glycoproteins from breast colostrum (BC) and 427 site‐specific N‐glycans attached to 60 serum glycoproteins from breast mature milk (BM) were identified and quantified using label‐free site‐specific glycoproteomics. Among them, 24 site‐specific N‐glycans mapping to 11 N‐glycosites on 9 glycoproteins were significantly increased, and 76 site‐specific N‐glycans mapping to 19 N‐glycosites on 13 glycoproteins were significantly decreased. Gene ontology annotation analysis showed that BC and BM serum N‐glycoproteins were mainly enriched in complement activation, classical pathway, extracellular exosome part, and immunoglobulin receptor binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that BC and BM serum N‐glycoproteins were mainly involved in the PI3K‐Akt signaling pathway. Additionally, breast milk serum N‐glycoproteins carried fucosylated core structures as well as Lewis and sialylated branch structures that may contribute to neonatal retinal homeostasis. These results provide a molecular basis for understanding the unique biological activities of breast milk serum N‐glycoproteins.

Abstract Objective The treatment of biliary tract (BTC) cancer remains relatively limited, especially in the setting of advanced BTC. Immune checkpoint inhibitors (ICIs) have shown some effects in a variety of solid tumors, but their efficacy and safety in patients with advanced BTC are still elusive, which require in‐depth analysis. Methods The clinical information of 129 patients diagnosed with advanced BTC between 2018 and 2021 were retrospectively reviewed. All patients were treated with chemotherapy, while a portion of them (64 patients) were treated with ICIs, the other 64 patients were not. Therefore, we divided the patients into two groups, SC (standard chemotherapy) and CI (chemotherapy in combined with immunotherapy), then we analyzed the benefit of adding ICIs according to efficacy, adverse events, progression‐free survival (PFS), progressive disease (PD), and the influence of various factors and effectiveness. Results The mean PFS was 9.67 months for CI group and 6.83 months for SC group. The PFS was prolonged by 2.84 months with ICI addition, and the difference was statistically significant (t = 3.114, 95% CI: 1.06–4.74, p

Abstract The solar‐driven interfacial evaporation (SIE) technology shows great prospects in seawater desalination and sewage treatment, but it is unable to obtain highly efficient and high‐quality clean nontoxic water at low cost. Here, a novel biodegradable hydrogel‐based solar evaporator (BBH‐L) with a bionic coral structure taking Chinese ink as the solar absorber was developed. This evaporator consists of chitosan/polyvinyl alcohol hydrogel and a loofah substrate. The average evaporation rate and efficiency of BBH‐L reach 4.37 kg/(m2·h) and 98.2%, respectively, under one sun illumination (1 kW/m2), which are attributed to its excellent thermal localization and water transporting abilities. Meanwhile, high salt resistance enables BBH‐L to achieve efficient desalination and purification of other unconventional water. Heavy metal ions in seawater can be effectively removed by chelation and forming hydrogen bonds in hydrogels. This study is anticipated to provide new possibilities to enhance evaporation performance and reduce the costs of water treatment systems.

Objective The surgical transepicondylar axis (sTEA) is believed to be a consistent reference for femoral rotation axis, and the reliability of its orientation seriously affects the accuracy and outcome of total knee arthroplasty (TKA). This study was designed to investigate the relationship between the orientation of sTEA and femoral bowing angle (FBA) and posterior condylar line (PCL) using three‐dimensional (3D) computed tomography (CT) reconstruction models to verify its reliability. Methods This study retrospectively collected lower extremity images of 443 southern Chinese osteoarthritic patients (347 women, 96 men; 234 left, 209 right; mean age 66.5 ± 9.3 years) from August 2016 to June 2018. The hip–knee‐ankle angle (HKA) was measured on anteroposterior weight‐bearing full lower extremity standing radiographs. Measurements on 3D CT models of the femurs included lateral angle between the femoral mechanical axis and sTEA coronal angle, angle between sTEA and distal joint line (distal condylar axis angle, DCA); angle between sTEA and PCL (sTEA axial angle); angle between anatomical axis of proximal femur and anatomical axis of distal femur in the plane they form (actual FBA) and its projection on the coronal (lateral FBA) and sagittal (anterior FBA) planes. The correlations between sTEA coronal angle, sTEA axial angle and actual FBA, lateral FBA, anterior FBA, HKA, DCA were explored using the Spearman correlation test. Results The mean value of actual FBA is (14.4 ± 3.6)°, of lateral FBA is (6.0 ± 4.0)°, and of anterior FBA is (12.7 ± 3.0)°. The mean value of sTEA coronal angle is (88.7 ± 3.6)°, of sTEA axial angle is (2.1 ± 2.8)°. The sTEA coronal angle was positively correlated with actual FBA (r = 0.320, P

Abstract Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first “tumor agnostic” drugs approved for pan‐cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second‐generation drugs designed to overcome first‐generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription‐polymerase chain reaction, and (DNA and/or RNA‐based) next‐generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first‐ and second‐generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

Objective Patellofemoral kinematics and contact mechanics are important measurements for the assessment of patellofemoral joint (PFJ) problems. Simultaneously measuring PFJ contact pressures and kinematics is a challenging task. The purpose of this study was to simultaneously measure the kinematics and mean/peak contact pressures in the PFJs of cadaveric knees. Methods This was a comparative study performed on fresh cadaveric knees. The kinematic data was acquired for nine cadaveric knees using an optical tracking system. Data about the contact pressure and contact area in the PFJ was obtained at knee flexion angles of 0°, 30°, 60°, 90°, and 120° using a pressure sensor. Intraclass correlation coefficients (ICCs) and minimal detectable differences (MDDs) of six degrees of freedom (6 DOF) in the PFJs were calculated. ICCs and the MDDs of contact pressure, peak pressure, and contact area in the PFJs were also analyzed. We also compared the kinematics of the cadaveric knees before and after the insertion of the pressure sensor. Results All ICC values of 6 DOF in the PFJs were found to be greater than or equal to 0.924. Regarding medial–lateral rotation, the patellar showed a simplified movement pattern that demonstrated progressive lateral rotation of 4.8° ± 3.4° at 120° of knee flexion. While for patellar tilting, the patella showed medial tilting that peaked at 7.2 ± 2.5° at 30° of knee flexion. Whereas no significant differences in PFJ kinematics were found between with and without the placement of the pressure sensor at all knee flexions (P > 0.05). Most of the ICC values for contact pressure, peak contact pressure, and contact area ranged from 0.8 to 0.9. The MDDs for rotational displacement were 0.9° and 0.6 mm for translational displacement. No statistical differences in patellar kinematics were found before and after the insertion of the pressure sensor. Conclusions The setup in the present study enables researchers to simultaneously and synchronously collect real‐time PFJ kinematics and tibiofemoral joint (TFJ) biomechanical kinematic data with high reliability. The low MDDs enabled the researchers to obtain an accurate interpretation of the kinematic and contact mechanics measurement using the experimental setting used in the present study.

Objective This study explored whether robotic arm‐assisted total knee arthroplasty (RATKA) has the advantage of restoring femoral rotational alignment compared to conventional total knee arthroplasty (COTKA). Methods Sixty patients (45 women and 15 men) attending our department from May 2019 to December 2020 were selected and divided into two groups, with 30 patients in each group, according to whether they underwent COTKA or RATKA. Femoral rotational alignment results, such as, posterior condylar angle (PCA), patella transverse axis‐femoral transepicondylar axis angle (PFA), radiological findings, such as, hip‐knee‐ankle angle (HKA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA), and operative data (operation time, intraoperative blood loss, tourniquet time, and length of stay (LOS), and clinical outcomes, such as maximum knee flexion angle (MKFA), Knee Society Score (KSS), and Western Ontario Mac Master University Index Score (WOMAC) were compared within and between the two groups. Results PCA and PFA in the RATKA group were (0.6 ± 0.3)° and (0.9 ± 0.3)°, respectively, which were smaller than (1.5 ± 2.0)° and (3.1 ± 1.1)° in the COTKA group (P

Abstract Aims Radiofrequency catheter ablation (RFCA) is now an established therapeutic option for patients with atrial fibrillation (AF), but the long‐term recurrence rate of AF is still high. Sacubitril/valsartan (Sac/Val) is superior to valsartan in attenuating ventricular remodelling and improving clinical outcomes in heart failure patients, but whether this additional benefit exists in reversing atrial remodelling and reducing AF recurrence of RFCA‐treated AF patients remains uncovered. Methods and results Patients that had undergone RFCA were enrolled and randomly assigned 1:1 to valsartan (160 mg/day) or Sac/Val (200 mg/day) treatment group, in addition to other standard treatment of AF. Patients were followed up for 24 weeks. Echocardiography and ambulatory Holter monitoring for 24 h was performed at 24 weeks after RFCA. The primary end point was the change of atrial diameter from baseline to 24 weeks after RFCA. Second end points included the recurrence rate of AF, all‐cause hospitalization and all‐cause death. A total of 64 AF patients were enrolled, 32 of which received Sac/Val and 32 received valsartan treatment. There was no difference in the age (64.8 ± 9.8 vs. 63.7 ± 9.0, P = 0.634), gender (per cent of male: 59.4% vs. 50.0%, P = 0.616), heart rate (84.7 ± 4.1 b.p.m. vs. 80.9 ± 2.6 b.p.m., P = 0.428), systolic (127.5 ± 15.4 mmHg vs. 130.0 ± 17.8 mmHg, P = 0.549) or diastolic (81.7 ± 9.8 mmHg vs. 79.9 ± 12.6, P = 0.537) blood pressure upon admission between valsartan and Sac/Val treatment groups. The percentage of persistent AF was also comparable (43.8% vs. 53.1%, P = 0.617) in both treatment groups. Patients receiving Sac/Val treatment displayed significant decrease in the left atrial diameter (4.3 ± 0.5 cm to 3.8 ± 0.5 cm, P

Abstract Long records of tree‐ring maximum latewood density (MXD) measurements in conifers have been successfully employed to reconstruct summer temperature changes globally. Yet, the potential of MXD as a proxy in semi‐arid, low‐latitude regions for reconstructing either temperature or hydroclimate variability remains largely unexplored. Here, we developed a MXD data set of Chinese pine from semi‐arid northern China, and investigated its sensitivity to different climate variables. We found that the annual self‐calibrated Palmer Drought Severity Index from previous August to current July displays the strongest influence on the MXD variation. The entire MXD chronology (covering 1736–2020) is highly consistent with nearby tree‐ring‐based annual precipitation and drought reconstructions at decadal timescales, confirming a temporally stable hydroclimate signal in our MXD record. In particular, the rapid wetting trend during the 2010–2020 period is well captured by the MXD data. This novel study has wide implications for future use of tree‐ring density data to reconstruct past climate changes globally.

Abstract As the lastly unexplored electromagnetic wave, terahertz (THz) radiation has been exploited in a plenty of contexts such as fundamental research, military and civil fields. Most recently, representative two‐dimensional (2D) topological semimetal, platinum ditelluride (PtTe2) has attracted considerable research interest in THz detection due to its unique physical properties. However, to achieve practical applications, the low‐cost, large‐scale, controllable synthesis and efficient patterning of 2D materials are key requirements, which remain a challenge for PtTe2 and its photodetectors (PDs). Herein, a facile approach is developed to obtain wafer‐scale (2‐inches) patterned PtTe2 arrays using one‐step tellurium‐vapor transformation method and micro‐Nano technology. PtTe2 PD arrays are fabricated with the as‐grown PtTe2 arrays evenly distributed on a 2‐inch wafer, exhibiting high conductivity (~2.7 × 105 S m−1) and good electrical consistency. Driven by the Dirac fermions, PtTe2 PDs achieve a broadband (0.02–0.3 THz) response with a fast response speed (~4.7 μs), a high sensitivity (~47 pW Hz−1/2) and high‐resolution transmission THz‐imaging capability, which displays the potential of large‐area THz array imaging. These results are one step towards the practical applications of integrated PD arrays based on 2D materials.

Abstract Genomics data analysis requires efficient tools to address the vast amount of data generated by current next‐generation sequencing technologies. K‐mer counting works face difficulties in balancing high memory overhead with statistical precision. We designed a high‐frequency k‐mer statistical computation based on the Space Saving algorithm and a novel hash table structure, which reduces the memory overhead by 46% while ensuring high computational efficiency.

Abstract Background We aimed to determine whether receptor tyrosine kinase‐like orphan receptor 2 (ROR2) is involved in the occurrence of acute lung injury (ALI) by an animal study and explore the effect of ROR2 downregulation on lipopolysaccharide (LPS)‐treated human lung carcinoma A549 cells by a cytological study. Methods Murine models of ALI were successfully constructed by intratracheal instillation of LPS. Meanwhile, A549 cell line stimulated with LPS was used for a cytological study. The expression of ROR2 and its effect on proliferation, cell cycle, apoptosis, and inflammation were detected. Results It was found that LPS administration markedly inhibited the cell proliferation, resulted in cell cycle arrest at G1 phage, elevated levels of pro‐inflammatory cytokines and apoptosis rate of A549 cells. However, LPS‐mediated adverse effects mentioned above were significantly ameliorated by downregulation of ROR2 in comparison with LPS treatment. In addition, administration of ROR2 siRNA notably decreased the phosphorylation level of c‐Jun N‐terminal kinase (JNK) and extracellular signal‐regulated kinase (ERK) in LPS‐challenged A549 cells. Conclusions Thus, the present data indicate that downregulation of ROR2 may decrease LPS‐induced inflammatory responses and cell apoptosis through inhibiting JNK and ERK signaling pathway, which attenuates ALI.

Abstract Two‐dimensional (2D) ferroelectrics have attracted considerable attention due to their potential in the development of devices of miniaturization and multifunction. Although several van der Waals (vdW)‐layered materials show ferroelectricity, the experimental demonstrations of ferroelectric behavior in monolayers are very limited. Here we report the observation of room‐temperature out‐of‐plane switchable electric polarization in supported MoS2 monolayers exfoliated from 3R‐stacked bulk crystals under ambient conditions. Using in situ piezoelectric force microscopy and Kelvin probe force microscopy in a glovebox, we reveal that trapped water/ice molecules are responsible for this switchable electric polarization and this conclusion is strongly supported by theoretical simulations. It is worth noting that the water/ice trapping in the monolayers exfoliated from 2H‐stacked MoS2 crystals is not as much as that in 3R monolayers and, consequently, the out‐of‐plane electric polarization is missing there. Our findings indicate that monolayers with a trapped single layer of polar molecules might be emerging alternatives to 2D ferroelectrics. Furthermore, the stacking sequences may bring new properties and applications to 2D vdW materials not only when we stack them up but also when we thin them down.

Abstract Objective This study aims to emphasize the initiating role of facet joint (FJ) degeneration in the process of cervical spine degeneration induced by tangential load, and we further validate it in a novel cervical spine degeneration animal model. Methods The characteristics of cervical degeneration in patients of different ages were summarized through case collection. In the rat models, Hematoxylin–Eosin, Safranin O staining, and micro‐computed tomography were used to show the histopathological changes and bone fiber structure of FJ and the height of intervertebral disc (IVD) space. The ingrowth of nociceptive sensory nerve fibers was observed by immunofluorescence staining. Results FJ degeneration without IVDs degeneration was more common in people with cervical spondylosis in young patients. The obvious degeneration phenotypes of the FJs preceded the IVDs at the same cervical segment in our animal model. The SP+ and CGRP+ sensory nerve fibers were observed in the articular subchondral bone of degenerated FJs and porous endplates of degenerated IVDs. Conclusion The FJ degeneration may act as the major contributor to cervical spine degeneration in young people. The dysfunction of functional unit of spine, not a certain part of IVD tissue, results in the occurrence of cervical degeneration and neck pain.

Background. Kynureninase (KYNU) is a potential prognostic marker for various tumor types. However, no reports on the biological effects and prognostic value of KYNU in gastric cancer (GC) exist. Methods. GC-associated single-cell RNA sequencing and bulk RNA sequencing (bulk-seq) data were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. The differential expression of KYNU between GC and normal gastric tissues was first analyzed based on the bulk-seq data, followed by an exploration of the relationship between KYNU and various clinicopathological features. The Kaplan–Meier survival and Cox regression analyses were performed to determine the prognostic value of KYNU. The relationship between KYNU expression and immune cell infiltration and immune checkpoints was also explored. The biological function of KYNU was further examined at the single-cell level, and in vitro experiments were performed to examine the effect of KYNU on GC cell proliferation and invasion. Results. KYNU expression was significantly elevated in GC samples. Clinical features and survival analysis indicated that high KYNU expression was associated with poor clinical phenotypes and prognosis, whereas Cox analysis showed that KYNU was an independent risk factor for patients with GC. Notably, high expression of KYNU induced a poor immune microenvironment and contributed to the upregulation of immune checkpoints. KYNU-overexpressing macrophages drove GC progression through unique ligand-receptor pairs and transcription factors and were associated with adverse clinical phenotypes in GC. KYNU was overexpressed in GC cells in vitro, and KYNU knockout significantly inhibited GC cell proliferation and invasion. Conclusion. High KYNU expression promotes an adverse immune microenvironment and low survival rates in GC. KYNU and KYNU-related macrophages may serve as novel molecular targets in the treatment of GC.

White matter damage (WMD) is a primary cause of cerebral palsy and cognitive impairment in preterm infants, and no effective treatments are available. Microglia are a major component of the innate immune system. When activated, they form typical pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes and regulate myelin development and synapse formation. Therefore, they may play a pivotal role in hypoxic–ischemic (HI) WMD. Herein, we investigated neural inflammation and long-term microglia phenotypic polarization in a neonatal rat model of hypoxia-ischemia-induced WMD and elucidated the underlying pathophysiological processes. We exposed 3-day-old (P3) Sprague−Dawley rats to hypoxia (8% oxygen) for 2.5 hr after unilateral common carotid artery ligation. The activation of NLRP3 inflammatory bodies, microglia M1/M2 polarization, myelination, and synaptic development in our model were monitored 7, 14, and 21 days after birth. In addition, the Morris water maze test was performed on postnatal Day 28. We confirmed myelination disturbance in the periventricular white matter, abnormal synaptic development, and behavioral changes in the periventricular area during the development of HI WMD. In addition, we found an association between the occurrence and development of HI WMD and activation of the NLRP3 inflammasome, microglial M1/M2 polarization, and the release of inflammatory factors. NLRP3 inhibition can play an anti-inflammatory role by inhibiting the differentiation of microglia into the M1 phenotype, thereby improving myelination and synapse formation. In conclusion, microglia are key mediators of the inflammatory response and exhibit continuous phenotypic polarization 7–21 days after HI-induced WMD. This finding can potentially lead to a new treatment regimen targeting the phenotypic polarization of microglia early after HI-induced brain injury.

Objective To investigate the efficacy of modified percutaneous Achilles tendon lengthening for severe ankle joint deformity. Methods This retrospective case series study included 33 patients with an average age of 25.2 years who underwent surgery in our hospital from April 1, 2010 to March 1, 2018. Triple hemisection percutaneous Achilles tendon lengthening was performed. One stage surgery, other soft tissue surgery or bone correction surgery could be performed. After surgery, a plaster cast was used to fix the functional position, and rehabilitation training was carried out as planned. Complications during the perioperative period were recorded. Statistical analysis of the patients' visual analogue scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) score before and at the last follow‐up was performed. The recurrence rate of Achilles tendon contracture at the last follow‐up and the patients' satisfaction rate were investigated. Results All patients were followed up, with an average follow‐up period of 56.31 months (8–104 months). All achieved good ankle joint function and appearance improvement And there were no infection or skin necrosis complications. In two cases, the incision was poorly healed at non‐Achilles tendon site and was cured by change of dressing. The average VAS score at the last follow‐up was reduced from (2 ± 1.48) points before surgery to (0.26 ± 0.51) points (P = 0.001), and the average AOFAS score was increased from (64.97 ± 13.56) points before surgery to (90.06 ± 10.06) points (P = 0.001). During the follow‐up period, there was no chronic rupture of Achilles tendon. There were two cases of recurrence of foot drop (5.7%), and the patients' satisfaction rate was 93.9%. Conclusion In the surgical treatment of severe ankle joint deformity, the application of triple hemisection percutaneous Achilles tendon lengthening for Achilles tendon contracture has the advantages of less trauma, beautiful incision, and reliable efficacy. The satisfaction rate of patients with this treatment is high, and it is worth promoting in the clinic.

Abstract Design procedure of a novel transmission line low‐pass filter is presented. The filter has a flexible rejection response for a prescribed cut‐off frequency and an in‐band ripple factor. It is compact by using a Z‐shaped coupled‐line section, which is loaded with open‐circuited stubs. All of the transmission line elements are identical in electrical length, and the impedances can be calculated by solving certain specific equations according to prescribed in‐band specifications. The simulated results show that the circuit can generate low‐pass responses with third‐, fifth‐, and seventh‐order filtering functions. The filter order depends on the number and position of the loading stubs. For verification, two sample filters with cut‐off frequency of 0.5/0.3 GHz are fabricated using a three‐/five‐layer PCB process, which generate seventh‐order low‐pass filtering responses with good selectivity. The experimental results agree well with the predictions.

Abstract Despite the interest toward the terahertz (THz) rapidly increasing, the high‐efficient detection of THz photon is not widely available due to the low photoelectric conversion efficiency at this low‐energy photon regime. Excitonic insulator (EI) states in emerging materials with anomalous optical transitions and renormalized valence band dispersions render their nontrivial photoresponse, which offers the prospect of harnessing the novel EI properties for the THz detection. Here, an EI‐based photodetector is developed for efficient photoelectric conversion in the THz band. High‐quality EI material Ta2NiSe5 is synthesized and the existence of the EI state at room temperature is confirmed. The THz scanning near‐field optical microscopy experimentally reveals the strong light–matter interaction in the THz band of EI state in the Ta2NiSe5. Benefiting from the strong light–matter interaction, the Ta2NiSe5‐based photodetectors exhibit superior THz detection performances with a detection sensitivity of ≈42 pW Hz−1/2 and a response time of ≈1.1 µs at 0.1 THz at room temperature. This study provides a new avenue for realizing novel high‐performance THz photodetectors by exploiting the emerging EI materials.

Abstract Background The melanocortin receptor accessory proteins (MRAP1 and MRAP2) are well‐known endocrine regulators for the trafficking and signalling of all five melanocortin receptors (MC1R–MC5R). The observation of MRAP2 on regulating several non‐melanocortin G protein‐coupled receptors (GPCRs) has been sporadically reported, whereas other endogenous GPCR partners of the MRAP protein family are largely unknown. Methods Here, we performed single‐cell transcriptome analysis and drew a fine GPCR blueprint and MRAPs‐associated network of two major endocrine organs, the hypothalamus and adrenal gland at single‐cell resolution. We also integrated multiple bulk RNA‐seq profiles and single‐cell datasets of human and mouse tissues, and narrowed down a list of 48 GPCRs with strong endogenous co‐expression correlation with MRAPs. Results 36 and 46 metabolic‐related GPCRs were consequently identified as novel interacting partners of MRAP1 or MRAP2, respectively. MRAPs exhibited protein–protein interactions and varying pharmacological properties on the surface translocation, constitutive activities and ligand‐stimulated downstream signalling of these GPCRs. Knockdown of MRAP2 expression by hypothalamic administration of adeno‐associated virus (AAV) packed shRNA stimulated body weight gain in mouse model. Co‐injection of corticotropinreleasing factor (CRF), the agonist of corticotropin releasing hormone receptor 1 (CRHR1), suppressed feeding behaviour in a MRAP2‐dependent manner. Conclusions Collectively, our study has comprehensively elucidated the complex GPCR networks in two major endocrine organs and redefined the MRAP protein family as broad‐spectrum GPCR modulators. MRAP proteins not only serve as a vital endocrine pivot on the regulation of global GPCR activities in vivo that could explain the composite physiological phenotypes of the MRAP2 null murine model but also provide us with new insights of the phenotyping investigation of GPCR–MRAP functional complexes.

Objective To report on the clinical outcome of patients undergoing combined arthroscopic treatment of labral resection and microfracture at the rim of acetabulum at a minimum 2‐year follow‐up. Methods The retrospective study included 38 patients undergoing hip arthroscopy for irreparable labral injury from 24 February 2014 to 26 February 2018. Thirteen patients were excluded owing to patient refusal of participation and concomitant diseases like synovial chondromatosis and dysplasia hip. The study group consisted of patients undergoing combined arthroscopic labral resection and microfracture at the rim of acetabulum (MICRO Group: 20 patients), arthroscopic labral resection alone (RESEC Group: five patients). Postoperative three‐dimensional (3D) double‐echo steady‐state (DESS) sequence with radial imaging at 3 Tesla were obtained and fluoroscopic image of the involved hip under distraction were used to observe the restoration of vacuum effect. Patient‐reported outcome scores (PROs) including the Harris Hip Score (HHS), Visual Analogue Score (VAS), Hip Outcome Score Activities of Daily Living Subscale (HOS‐ADL), Hip Outcome Score Sport‐Specific Subscale (HOS‐SSS) were collected and compared between two groups. Results All patients were followed up for at least 6 months. The follow‐up time of RESEC group is longer than MICRO group (46.6 months vs 23.9 months, P

Abstract The interface structure of the electrode is closely related to the electrochemical performance of lithium‐metal batteries (LMBs). In particular, a high‐quality solid electrode interface (SEI) and uniform, dense lithium plating/stripping processes play a key role in achieving stable LMBs. Herein, a LiF‐rich SEI and a uniform and dense plating/stripping process of the electrolyte by reducing the electrolyte concentration without changing the solvation structure, thereby avoiding the high cost and poor wetting properties of high‐concentration electrolytes are achieved. The ultra‐low concentration electrolyte with an unchanged Li+ solvation structure can restrain the inhomogeneous diffusion flux of Li+, thereby achieving more uniform lithium deposition and stripping processes while maintaining a LiF‐rich SEI. The LiIICu battery with this electrolyte exhibits enhanced cycling stability for 1000 cycles with a coulombic efficiency of 99% at 1 mA cm–2 and 1 mAh cm–2. For the LiIILiFePO4 pouch cell, the capacity retention values at 0.5 and 1 C are 98.6% and 91.4%, respectively. This study offers a new perspective for the commercial application of low‐cost electrolytes with ultra‐low concentrations and high concentration effects.

Background Although the association between shift work and individual cardiometabolic diseases has been well studied, its role in the progression to cardiometabolic multimorbidity (CMM) remains unclear. In this study, we investigate the association between shift work and the incidence of CMM in patients with hypertension. Methods and Results This study is a population‐based and prospective cohort study on 36 939 UK Biobank participants. We used competing risk models to examine the association between shift work and the risk of CMM, which was defined as coexistence of hypertension and diabetes, coronary heart disease, or stroke in our study. We also investigated the association between the frequency and duration of shift work and CMM risks. In addition, we conducted a cross‐classification analysis with the combination of frequency and duration of shift work, chronotype and sleep duration as the exposure metrics. During a median follow‐up of 11.6 years, a total of 5935 participants developed CMM. We found that usually/always night shift workers were associated with a 16% higher risk of CMM compared with day workers (hazard ratio [HR], 1.16 [95% CI, 1.02–1.31]). We also found that a higher frequency of night shifts (>10/month) was associated with increased risk of CMM (HR, 1.19 [95% CI, 1.06–1.34]) that was more pronounced for >10/month in combination with a morning chronotype or 8 hours of sleep duration (HR, 1.26 [95% CI, 1.02–1.56]; HR, 1.43 [95% CI, 1.19–1.72], respectively). Conclusions We find that night shift work is associated with higher CMM risk in patients with hypertension.

Abstract We aimed to identify skipjack elastin hydrolysate‐derived peptides, and explore its mechanism of photoprotection against ultraviolet A (UVA) induced skin damage. Two peptides, TGVLTVM (peptide A) and NHIINGW (peptide B), were successfully identified using Sephadex G‐15, analyzed and detected using LC‐MS/MS fitted with electrospray ionization (ESI‐MS/MS), and further synthesized using the Fmoc strategy. A UVA radiation‐induced damage cell model of Human keratinocytes cell line (HaCaT) was established and applied. We found that both peptides significantly reduced reactive oxygen species (ROS) generation, reversed mitochondrial membrane potential (MMP) by 12.40%–13.13% and 10.80%–12.90% and reduced cell apoptosis by 3.43%–6.44%, and 4.56%–6.03% for peptide A and B, respectively, compared to the UVA model group. In conclusion, peptides TGVLTVM and NHIINGW protected against UVA‐induced photoaging through the attenuation of oxidative stress, thus both peptides might be useful as promising ingredients in sunscreens or antiaging cosmetic products.

Thyroid dysgenesis (TD) is a major cause of primary congenital hypothyroidism; however, the molecular mechanism underlying this process is unclear. Current knowledge regarding the morphogenesis of the thyroid gland and vascular anomalies affecting thyroid development is limited. To monitor the early stages of thyroid gland development, we generated double transgenic zebrafish embryos Tg(tg:mCherry/flk1:EGFP). We described the volume of the thyroid from 2 days postfertilization (dpf) to 5 dpf using 3D reconstruction images. We treated zebrafish embryos with the fibroblast growth factor (FGF) inhibitor PD166866 to better understand the impact of vascular defects on thyroid development and the effects of drug administration at specific time periods on different stages of thyroid development. The 3D reconstruction data revealed that the thyroid glands underwent significant transformation at critical time points. PD166866 treatment from 48 to 72 hours postfertilization (hpf) and from 72 to 96 hpf did not cause obvious reductions in thyroid volume but did result in observable abnormalities in thyroid morphology. The treatment also affected thyroid volume from 36 to 48 hpf, thus indicating that there are time‐point‐specific effects of drug administration during thyroid development. Three‐dimensional image reconstruction provides a comprehensive picture of thyroid anatomy and can be used to complement anatomical fluorescence information. The effects of an FGF pathway inhibitor on thyroid development were determined to be time‐point‐dependent.

Abstract Untethered small robots with multiple functions show considerable potential as next‐generation catheter‐free systems for biomedical applications. However, owing to dynamic blood flow, even effective upstream swimming in blood vessels remains a challenge for the robot, let alone performing medical tasks. This paper presents an untethered millirobot with a streamlined shape that integrates the engine, delivery, and biopsy modules. Based on the proposed spiral‐rolling strategy, this robot can move upstream at a record‐breaking speed of ≈14 mm s−1 against a blood phantom flow of 136 mm s−1. Moreover, benefiting from the bioinspired self‐sealing orifice and easy‐open auto‐closed biopsy needle sheath, this robot facilitates several biomedical tasks in blood vessels, such as in vivo drug delivery, tissue and liquid biopsy, and cell transportation in rabbit arteries. This study will benefit the development of wireless millirobots for controllable, minimally invasive, highly integrated, and multifunctional endovascular interventions and will inspire new designs of miniature devices for biomedical applications.

Abstract Reclamation of cropland from grassland is regarded as a main reason for grassland degradation; understanding succession from abandoned cropland to grassland is thus crucial for vegetation restoration in arid and semiarid areas. Soil becomes dry when cropland is reverted to grassland, and enzyme and osmotic adjustment compounds may help plants to adapt to a drying environment. Croplands that were abandoned in various years on the Ordos Plateau in China, were selected for the analysis of the dynamics of enzymes and osmotic adjustment compounds in plant species during vegetation succession. With increasing number of years since abandonment, levels of superoxide dismutase increased in Stipa bungeana, first decreased and then increased in Lespedeza davurica and Artemisia frigida, and fluctuated in Heteropappus altaicus. Levels of peroxidase and catalase in the four species fluctuated; levels of proline, soluble sugar, and soluble protein either decreased or first increased and then generally decreased. According to a drought resistance index, the drought resistance of the four species was ranked in descending order as follows: S. bungeana > A. frigida > H. altaicus > L. davurica. The drought resistance ability of the different species was closely linked with vegetation succession from communities dominated by annual and biennial species (with main accompanying species of L. davurica and H. altaicus) to communities dominated by perennial species (S. bungeana and A. frigida) when soil became dry owing to increasing evapotranspiration after cropland abandonment. The restoration of S. bungeana steppe after cropland abandonment on the Ordos Plateau is recommended both as high‐quality forage and for environmental sustainability.

Hepatocellular carcinoma (HCC) with high heterogeneity is one of the most frequent malignant tumors. However, there were no studies to create a clinical stage-related gene signature for HCC patients. Differentially expressed genes (DEGs) associated with clinical stage of HCC were analyzed based on TCGA datasets. Functional enrichment analysis was carried out by the use of stage-related DEGs. Then, the least absolute shrinkage and selection operator (LASSO) regression and univariate Cox regression were performed to reduce the overfit and the number of genes for further analysis. Next, survival and ROC assays were carried out to demonstrate the model using TCGA. Functional analysis and immune microenvironment analysis related to stage-related DEGs were performed. Reverse transcriptase polymerase chain reaction (RT-PCR) and Cell Counting Kit-8 (CCK-8) assays were applied to examine the expression and function of PNCK in HCC. In this research, there were 21 DEGs between HCC specimens with stage (I-II) and HCC specimens with stage (III-IV), including 20 increased genes and 1 decreased genes. A novel seven-gene signature (including PITX2, PNCK, GLIS1, SCNN1G, MMP1, ZNF488, and SHISA9) was created for the prediction of outcomes of HCC patients. The ROC curves confirmed the prognostic value of the new model. Cox assays demonstrated that the seven-gene signature can independently forecast overall survival. The immune analysis revealed that patients with low risk score exhibited more immune activities. Moreover, we confirmed that PNCK expressions were distinctly increased in HCC, and its silence suppressed the proliferation of HCC cells. Overall, our research offered a robust and reliable gene signature which displayed an important value in the prediction of overall survival of HCC patients and might deliver more effective personalized therapies.

Chronic obstructive pulmonary disease (COPD) has high morbidity and mortality and presents a threat to human health worldwide. Numerous clinical trials have confirmed that Bufei Yishen formula (BYF), an herbal medicine, can alleviate the symptoms of COPD by reducing oxidative stress-mediated inflammation. However, the active components of BYF remain unclear. We developed an efficient ultrahigh-performance liquid chromatography Q-Extractive Orbitrap mass spectrometry method to identify the composition of BYF and determine its antioxidant profile through an offline screening strategy based on 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH)-liquid chromatography-mass spectrometry. In total, 189 compounds were identified in BYF extract, including 83 flavonoids, 24 lignans, 20 alkaloids, 15 saponins, 11 terpenoid, 10 saccharides, eight lipids, seven organic acids, two coumarins, two amino acids, and seven other compounds. Among them, 79 compounds were found to have a potential antioxidant activity. In vitro validation indicated that the free radical scavenging activities of rosmarinic acid and calycosin were similar to that of the positive control (DPPH IC50 = 25.72 ± 1.02 and 147.23 ± 25.12 μg/mL, respectively). Furthermore, calycosin had a high content in serum after the oral administration of BYF, indicating that calycosin might be the major antioxidant compound in BYF.

Schwann cells have been found to promote osteogenesis by an unclear molecular mechanism. To better understand how Schwann cells accelerate osteogenesis, RNA-Seq and LC-MS/MS were utilized to explore the transcriptomic and metabolic response of MC3T3-E1 to Schwann cells. Osteogenic differentiation was determined by ALP staining. Lentiviruses were constructed to alter the expression of Mif (macrophage migration inhibitory factor) in Schwann cells. Western blot (WB) analysis was employed to detect the protein expression. The results of this study show that Mif is essential for Schwann cells to promote osteogenesis, and its downstream CD74/FOXO1 is also involved in the promotion of Schwann cells on osteogenesis. Further, Schwann cells regulate amino acid metabolism and lipid metabolism in preosteoblasts. These findings unveil the mechanism for Schwann cells to promote osteogenesis where Mif is a key factor.

Oil sand is an important substitute for conventional oil resources. In this paper, oil sand cores are used to systematically study the mesostructure characteristics of oil sand. Triaxial compression tests under different temperatures and pressures are carried out on oil sand specimens. The research results show that the mineral particles in these oil sands have a loose structure. The particle size distribution of the mineral particles has good continuity. The prepeak deformation characteristics of these oil sands are similar. However, three kinds of postpeak deformation forms are observed: plastic flow, strain softening, and strain hardening. Increasing the temperature can enhance the shear dilatation rate, and the shear dilatation rate decreases nonlinearly with increasing confinement. The compressive strength, residual strength, and elastic modulus increase linearly with increasing confinement. Temperature has little effect on the strength and elastic modulus of oil sand, but it can significantly affect the corresponding Poisson’s ratio. The failure modes of oil sand are dominated by shear failure and tensile failure. Under the test condition of 120°C, the thermal stress generated by the high temperature causes the oil sand specimens to produce transverse cracks. These results can provide relevant parameters for the design of oil sand exploration technology.

To satisfy the adaptability of forecasting the short-term and abrupt volume of the initial metro network, we build the multiple enter linear regression (MELR) model to explore the determinants and forecast the intensity during the twice expansion of the initial metro network in Xi’an. We further compare the prediction of the metro transport capacity between the MELR models with exponential smoothing and autoregressive integrated moving average (ARIMA) models. Results show that the passenger intensity significantly fluctuates with the months and days, and MELR model is more adapted for the short-term prediction of the abrupt volume than the ARIMA model during the new metro line opening and the old line expands, which avoids the drawback of time series models that need a huge database. This study provides a guide for the prediction of initial metro network volume and accurate purchase of the rail vehicles during the metro planning and expends stages.

Background. BRAF exon 15 p.V600E (BRAF V600E) mutation has been established as an important molecular marker for papillary thyroid carcinoma diagnosis by ultrasound-guided fine-needle aspiration biopsy (FNAB). Sanger sequencing is the gold standard for detecting BRAF V600E mutations but fails to identify low-frequency mutations. However, droplet digital PCR (ddPCR) is a popular new method for detecting low-frequency mutations. Here, we compare the efficiency of droplet digital PCR (ddPCR) and Sanger sequencing for detection of the BRAF V600E mutation in thyroid fine-needle aspiration (FNA) samples. Methods. Thyroid fine-needle aspiration samples from 278 patients with 310 thyroid nodules were collected. Sanger sequencing and ddPCR were conducted to detect the BRAF V600E mutation. Results. The BRAF V600E mutation was found in 94 nodules (30.32%) by ddPCR and 40 nodules (12.90%) by Sanger sequencing in 310 FNA samples. A total of 119 nodules were confirmed PTC by postsurgical pathology. Among which the BRAF mutation was found in 80 (67.23%) nodules by ddPCR and 31 (26.05%) by Sanger sequencing. All nodules carrying the mutation detected by Sanger sequencing (SS+) were verified by ddPCR (ddPCR+). Also, all nodules with no mutation detected by ddPCR were interpreted as wild-type by Sanger sequencing (SS−). In addition. Almost all SS+/ddPCR + nodules (95.00%; 38/40) and SS−/ddPCR + nodules (100.00%; 54/54) displayed a BRAF mutation rate of >5% and

Background. In recent years, the incidence of depression is on the rise. Our paper proposed to study the protective effects of Schisandrin on CORT-induced PC12 depressive cell model and the underlying mechanisms. Methods. The in vitro models of PC12 were established using corticosterone (CORT). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to screen the effective concentration of Schisandrin, and the models of PC12 were treated with low, medium, and high concentrations of Schisandrin. The cell activity of each group was detected by MTT assay. The LDH activity in each group of cells was detected by lactate dehydrogenase (LDH) kit. Apoptosis rate of each group was detected by Annexin V-FITC apoptosis assay kit. Mitochondrial membrane potential of each group of cells was detected by mitochondrial membrane potential kit. The protein expression levels of Caspase-3, Bax, and Bcl-2 in each group of cells were detected by western blot. Results. The treatment of Schisandrin significantly increased the cell viability in models of PC12. In addition, the results of LDH activity suggested that Schisandrin significantly reduced LDH content in models of PC12. Consistently, Schisandrin reduced the mitochondrial membrane potential of CORT-induced PC12 depressive cell model. Furthermore, Schisandrin effectively reduced the number of apoptotic cells and inhibited the expression of proapoptotic-related proteins (cleaved Caspase-3 and Bax) but increased the antiapoptotic-related protein (Bcl-2) in the models of PC12. Conclusions. Protective effects of Schisandrin on CORT-induced PC12 depressive cell model by inhibiting cells apoptosis in vitro.

Abstract Background Thoracic aortic aneurysm and dissection (TAAD) is a life‐threatening pathology that remains a challenge worldwide. Up to 40% of TAAD cases are hereditary with complex heterogeneous genetic backgrounds. The purposes of this study were to determine the diagnostic rate of patients with TAAD, investigate the molecular pathologic spectrum of TAAD by next‐generation sequencing (NGS), and explore the future preclinical prospects of genetic diagnosis in patients at high ‐risk of study. Methods NGS was used to screen 15 genes associated with genetic TAAD in 212 patients from northwestern China. Clinical data of patients were gathered by electrocardiography, transthoracic echocardiography, and computed tomography. Results Of the 212 patients, 67 (31.60%) tested positive for a (likely) pathogenic variant, 42 (19.81%) had a variant of uncertain significance (VUS), and 103 (48.58%) had no variant (likely benign/benign/negative). A total of 135 reportable variants were detected in our test, among which 77 (57.04%) are first reported in this paper. A genotype–phenotype correlation of FBN1 was assessed, and the data showed that the patients with truncating and splicing mutations are more prone to developing severe aortic dissection than those with missense mutations, especially frameshift mutations (82.76% vs. 42.86%). In this study, 43 (20.28%) patients had a family history of sudden death or TAAD, whereas 132 (62.26%) did not (the remaining 37 were not available), and the positive rate of genetic testing was higher in TAAD patients with family history than in those without (76.74% vs. 18.94%). Conclusion Our study concludes that genetic variation is an important consideration in the risk stratification of individualized prediction and disease diagnosis.

Abstract Malignant cancer cells engage in a dynamic reciprocity with the tumor microenvironment (TME) that promotes tumor growth, development, and resistance to therapy. Early embryonic blastocyst microenvironments can reverse the tumorigenic phenotype of malignant cancer cells via ameliorating of TME. It is potential to apply embryonic stem cell (ESC) microenvironment to suppress the malignant behaviors of cancer cells. This study aimed to investigate a better method and the mechanism of ESC microenvironment supplied by ESCs on suppressing the malignancy of cutaneous melanoma cells. Cutaneous melanoma cell line A2058 were cultured and divided into four groups: (a) A2058‐only (Control); (b) A2058 and ESCs continuously co‐cultured (Group One); (c) A2058 co‐cultured with daily refreshed ESCs (Group two); (d) Group one with VO‐Ohpic, inhibitor of PTEN (VO‐Ohpic Group). The results showed that, compared to control group, A2058 cells in group one exhibited decreased cellular proliferation, migration, invasiveness and vasculogenic mimicry concomitant with an increase in cell apoptosis, accompanied by down‐regulation of PI3K/AKT pathway. Besides, the above mentioned anti‐tumor effects on A2058 cells were significantly enhanced in group two but statistically weakened after administration of VO‐Ohpic compared to group one. We demonstrate that ESC microenvironment reduces the malignancy of A2058 by down‐regulating PI3K/AKT pathway. Notably, such anti‐tumor effects can be enhanced by appropriately increasing the quality and quantity of ESCs in co‐culture system. Our results suggest that ESC microenvironment could be an effective and safe approach to treating cancer.

Abstract Cancer‐testis (CT) genes are a group of genes restrictedly expressed in testis and multiple cancers and can serve as candidate driver genes participating in the development of cancers. Our previous study identified a number of CT genes in nongerm cell tumors, but their expression pattern in testicular germ cell tumor (TGCT), a cancer type characterized by less genomic alterations, remained largely unknown. In this study, we systematically investigated the expression pattern of CT genes in TGCT samples and evaluated the transcriptome difference between TGCT and normal testis tissues, using datasets from the UCSC Xena platform, The Cancer Genome Atlas (TCGA) and the Genotype‐Tissue Expression (GTEx) project. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of expressed CT genes. We identified that 1036 testis‐specific expressed protein‐coding genes and 863 testis‐specific expressed long noncoding RNAs (lncRNAs) were expressed in TGCT samples, including 883 CT protein‐coding genes and 710 CT lncRNAs defined previously. The number of expressed CT genes was significantly higher in seminomas (P = 3.48 × 10−13) which were characterized by frequent mutations in driver genes (KIT, KRAS and NRAS). In contrast, the number of expressed CT genes showed a moderate negative correlation with the fraction of copy number altered genomes (cor = −0.28, P = 1.20 × 10−3). Unlike other cancers, our analysis revealed that 96.16% of the CT genes were down‐regulated in TGCT samples, while CT genes in stem cell maintenance related pathways were up‐regulated. Further survival analysis provided evidence that CT genes could also predict the prognosis of TGCT patients with both disease‐free interval and progression‐free interval as clinical endpoints. Taken together, our study provided a global view of CT genes in TGCT and provided evidence that CT genes played important roles in the progression and maintenance of TGCT.

Objective To explore the feasibility of 3D printed customized guides assisting the precise drilling of Kirschner wires in subtalar joint arthrodesis. Methods We retrospectively reviewed the data of 29 patients (30 subtalar joints) who underwent subtalar joint arthrodesis between 1 July 2013 and 31 December 2017. The customized guides were designed on a full‐scale 3D polylactic acid model made from computed tomography (CT) data of patients by Model Intestinal Microflora in Computer Simulation (MIMICS) software, which were manufactured by 3D printing technology. A total of 14 joints used customized guides (experimental group); the remained 16 joints used the traditional method (control group). The time of drilling the Kirschner wires to the correct position, the time of subtalar fusion, American Orthopaedic Foot & Ankle Society (AOFAS) scores, and complications were evaluated in both groups. Results All customized guides were successfully manufactured. In the experimental group, it took 2.1 ± 0.7 min to drill the Kirschner wire to the satisfactory position, and 2 cases needed to be re‐drilled; in the control group, it took 4.6 ± 1.9 min to drill the Kirschner wire to the satisfactory position (P 0.05). Conclusion It is safe to apply 3D‐printed customized guides for subtalar joint arthrodesis, which can assist the accurate drilling of Kirschner wires into the appropriate position according to the preoperative plan, and reduce the operation time as well as intraoperative radiation.

Objective To evaluate the surgical results of V‐Y tendon plasty in the treatment of chronic Achilles tendon rupture during medium and long‐term follow‐up. Methods Between June 2005 and September 2017, 20 patients with chronic Achilles tendon rupture underwent V‐Y tendon plasty in our hospital. The mean injury‐to‐surgery time was 20.4 weeks (range, 4–96 weeks). The Matles test and an improved Thompson test was used to examine Achilles tendon rupture. These patients were not able to stand on the tiptoes of the injured lower extremity. X‐ray tests ruled out the chance of fracture and were used to examine the Kager triangle. MRI was used to confirm the final diagnosis. The function of the ankle and the foot was assessed using the American Orthopaedic Foot & Ankle Society (AOFAS) score and the Achilles Tendon Total Rupture Score (ATRS). V‐Y tendon plasty for Achilles tendon reconstruction was performed. A below‐knee cast was used to keep the ankle in plantar flexion (up to 20°) for 4 weeks. Non‐weight‐bearing exercise was allowed with crutches. After 4 weeks, partial weight‐bearing was allowed. Physical exercises were performed under rehabilitation guidelines. At 10–12 weeks postoperation, patients began to return to daily life activity levels without restrictions. Preoperative and postoperative MRI was obtained. Results The mean follow‐up period was 32.8 months. The mean operative gap of the Achilles tendon after debridement was 5 cm (range, 4–9 cm), with 85% of the gap less than or equal to 6 cm. The mean AOFAS score increased from 59.25 ± 12.28 preoperatively to 96.55 ± 3.75 at final follow‐up (P < 0.05). The mean ATRS score increased from 39.55 ± 14.21 preoperatively to 94.05 ± 4.89 at final follow‐up (P < 0.05). All patients had no recurrent Achilles tendon rupture during the follow up. No patient had developed serious complications, such as sural nerve injury or deep vein thrombosis. Patients were able to return to daily life activity levels without restrictions. At the latest follow‐up, all patients were able to perform repetitive single heel rise on the involved limb, and to walk without a visible limp. All of the postoperative MRI showed the continuity of the Achilles tendon with no signs of cysts or inflammation, indicating perfect healing at the final follow‐up. Conclusions V‐Y tendon plasty can be used in most cases of chronic Achilles tendon rupture. It yields satisfactory functional results and low complication rates. The advantage of this procedure is that it is an easy and economic method without the need for expensive synthetic implants. V‐Y tendon plasty should be considered an acceptable first‐choice treatment.

Developing small‐scale soft continuum robots with large‐angle steering capacity and high‐precision manipulation offers broad opportunities in various biomedical settings. However, existing continuum robots reach the bottleneck in actuation on account of the contradiction among small size, compliance actuation, large tender range, high precision, and small dynamic error. Herein, a 3D‐printed millimeter‐scale soft continuum robot with an ultrathin hollow skeleton wall (300 μm) and a large inner‐to‐outer ratio (0.8) is reported. After coating a thin ferromagnetic elastomer layer (≈100–150 μm), the proposed soft continuum robot equipped with hybrid actuation (tendon‐ and magnetic‐driven mode) achieves large‐angle (up to 100°) steering and high‐precision (low to 2 μm for static positioning) micromanipulation simultaneously. Specifically, the robot implements an ultralow dynamic tracking error of ≈10 μm, which is ≈30‐fold improved than the state of art. Combined with a microneedle/knife or nasopharyngeal swab, the robot reveals the potential for versatile biomedical applications, such as drug injection on the target tissue, diseased tissue ablation, and COVID‐19 nasopharyngeal sampling. The proposed millimeter‐scale soft continuum robot presents remarkable advances in large‐range and high‐precise actuation, which provides a new method for miniature continuum robot design and finds broad applications in biomedical engineering.

To study the effects of anisotropy and heterogeneity on the shale failure mode and tensile strength, Brazilian splitting tests were performed from both directions of the bedding and layer thickness. Layers containing different bedding and loading angles and layer thicknesses were obtained separately. The results show that, at 0° and 90° angles, the shale cracks grow “linearly”; at 15°, the shale cracks have “arc type” growth; and at 30°–75°, the shale-splitting displays “broken line” crack propagation. The tensile strength from 0° to 90° exhibits an increasing trend. Water has a significant softening effect on the tensile strength of shale—the higher the water content, the lower the tensile strength. In addition, a 3DEC numerical simulation was used to simulate the tests, establishing shale specimen particles with random blocks. In the shale disc, uneven parallel bedding and uniform parallel bedding were set up with different loading angles and layer thicknesses to generate simulated stress-displacement curves, and the effect of layering on shale cleavage was analyzed from a mesoscopic perspective. The tensile strength of shale with uniform parallel bedding was found to be higher under the same conditions, which is consistent with the experimental results. By comparing the experimental and simulation results, from both the macro- and mesoperspectives, the Brazilian splitting crack growth of shale is affected by bedding, displaying a process from disorder to order. This study is of great significance for further exploration of the mechanical properties of shale under loading failure.

The change of water quality can reflect the important indicators of ecological environment measurement. Sewage discharge is an important factor causing environmental pollution. Establishing an effective water ecological prediction model can detect changes in the ecological environment system quickly and effectively. In order to detect high error rate and poor convergence of the water ecological chemical oxygen demand (COD) prediction model, combining the limit learning machine (ELM) model and whale optimization algorithm, CAWOA is improved by the sin chaos search strategy, while the ELM optimizes the parameters of the algorithm to improve convergence speed, thus improving the generalization performance of the ELM. In the CAWOA, the global optimization results of the WOA are promoted by introducing a sin chaotic search strategy and adaptive inertia weights. On this basis, the COD prediction model of CAWOA-ELM is established and compared with similar algorithms by using the optimized ELM to predict the water ecological COD in a region. Finally, from the experimental results of the CAWOA-ELM algorithm, it has excellent prediction effect and practical application value.

We report a 15-year-old boy with cat-eye syndrome (CES) without short stature or intellectual disorder. The boy was confirmed by cytogenetic and high-resolution chromosome microarray analysis (CMA). The G-banding karyotype confirmed the de novo of the patient. Also, the CMA result showed 1.76 Mb tetrasomy of proximal 22Q11.1 ⟶ 22Q11.21 consistent with CES {arr22q11.1q11.21 (16,888,899–18,644,241) X4}, a typical small type I CES chromosome. The patient has many of the basic characteristics of CES; however, he is taller than his peers instead of shorter. It is rarely reported in the past since short stature is a common feature of this syndrome. Furthermore, the boy has no intellectual disorder and attends a normal school since he was six-year-old. What bothered him most were recurrent respiratory infections, retromicrognathia, and heart defects.

Soldier pile support is an important tool for supporting deep foundation pits in the sand-gravel layer. However, since the sand-gravel layer itself is an aggregate of particles, its noncontinuity will cause extremely complex changes in the properties of the surrounding soils during pile supporting, and the changes in the mechanical properties of the soil behind the piles can also affect the safety and stability of the pit. To study the changing pattern of the surrounding soil in the course of pile supporting, we used the numerical method to simulate an excavation in the sand-gravel layer, followed by an analysis of the movement and stress distribution of the surrounding rocks. A photoelastic experiment was carried out to simulate the excavation process and study the force chain network of the surrounding soil as well as its changing characteristics. As shown by the results, (1) during the excavation of a deep foundation pit supported by soldier piles, on the same horizontal plane, the force chain changed most dramatically at the position that was 13.8 m (depth of the foundation pit) away from the edge of the foundation pit; (2) during the excavation, the force chain structure of the surrounding soil changed from vertical development to both vertical and horizontal developments; when there was a hard rock layer at the bottom of the soldier piles, the supporting effect of the piles was mainly provided by the hard rock layer; (3) the free face should be reinforced, and the excavation face should be adjusted based on the underground conditions of surrounding buildings (structures).

Malan loess in the middle and lower reaches of the Yellow River after mixed with different bentonite and HDTMA ratios was selected to carry out shear and consolidation tests for discussing the influence of bentonite-HDTMA on the mechanical property of loess lining material in landfills. Studies have shown that, after mixing 6% to 14% bentonite, the cohesive force of modified loess is significantly increased, the friction angle is reduced and remains stable, and the shear strength is improved. The compressibility of materials slightly decreases with the increase of bentonite ratio. The addition of 2%–4% HDTMA weakens the increment for the cohesive force caused by bentonite, but the friction angle is effectively recovered. The compressibility of materials increases with the increase of HDTMA ratio. As the dry density increases, the shear strength of the modified loess increases, and the compressibility coefficient decreases. The mechanical property of loess lining material can be optimized by adding 6%–14% bentonite. The incorporation of 2%–4% HDTMA does not have a significant negative impact on the optimization effect of bentonite. From the perspective of the mechanical property, it is recommended that the dry density of modified loess is 1.70 g/cm3, the bentonite ratio is 10%–14%, and the HDTMA ratio is 2%–4%.