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Abstract It is important to study the effect of hydrate production on the physical and mechanical properties of low‐permeability clayey–silty reservoirs for the large‐scale exploitation of hydrate reservoirs in the South China Sea. In this study, a multiphysical‐field coupling model, combined with actual exploration drilling data and the mechanical experimental data of hydrate cores in the laboratory, was established to investigate the physical and mechanical properties of low‐permeability reservoirs with different slope angles during 5‐year hydrate production by the depressurization method via a horizontal well. The result shows that the permeability of reservoirs severely affects gas production rate, and the maximum gas production amount of a 20‐m‐long horizontal well can reach 186.8 m3/day during the 5‐year hydrate production. Reservoirs with smaller slope angles show higher gas production rates. The depressurization propagation and hydrate dissociation mainly develop along the direction parallel to the slope. Besides, the mean effective stress of reservoirs is concentrated in the near‐wellbore area with the on‐going hydrate production, and gradually decreases with the increase of the slope angle. Different from the effective stress distribution law, the total reservoir settlement amount first decreases and then increases with the increase of the slope angle. The maximum settlement of reservoirs with a 0° slope angle is up to 3.4 m, and the displacement in the near‐wellbore area is as high as 2.2 m after 5 years of hydrate production. It is concluded that the pore pressure drop region of low‐permeability reservoirs in the South China Sea is limited, and various slope angles further lead to differences in effective stress and strain of reservoirs during hydrate production, resulting in severe uneven settlement of reservoirs.

Abstract Background Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL‐S) is a rare autosomal dominant systemic microvascular disorder attributed to TREX1 (three‐prime repair exonuclease‐1) gene mutations, often proned to misdiagnosed. Methods We reported a case of RVCL‐S coexisting with systemic lupus erythematosus due to a mutation in the TREX1 gene. This study provided a summary and discussion of previously documented cases related to TREX1 mutations or RVCL‐S. Results A 39‐year‐old female patient visited the clinic due to progressive memory loss and speech difficulties. Magnetic resonance imaging results showed corpus callosum atrophy and multiple subcortical calcifications in both brain hemispheres. Genetic testing revealed a TREX1 gene mutation (c.294dupA). Treatment with immunosuppressive therapy for 2 months led to improvements in communication and mobility. We also summarized previously reported cases providing an overview of TREX1 gene mutation or RCVL‐S. Conclusion Our case establishes a compelling foundation for future RVCL‐S diagnosis and treatment paradigms. Notably, conducting systemic immunity screening in patients with RVCL‐S emerges as a strategic approach to prevent potential diagnostic oversights.

Abstract All‐solid‐state batteries equipped with solid‐state electrolytes (SSEs) have gained significant interest due to their enhanced safety, energy density, and longevity in comparison to traditional liquid organic electrolyte‐based batteries. However, many SSEs, such as sulfides and hydrides, are highly sensitive to water, limiting their practical use. As one class of important perovskites, the Ruddlesden–Popper perovskite oxides (RPPOs), show great promise as SSEs due to their exceptional stability, particularly in terms of water resistance. In this review, the crystal structure and synthesis methods of RPPOs SSEs are first introduced in brief. Subsequently, the mechanisms of ion transportation, including oxygen anions and lithium‐ions, and the relevant strategies for enhancing their ionic conductivity are described in detail. Additionally, the progress made in developing flexible RPPOs SSEs, which are critical for flexible and wearable electronic devices, has also been summarized. Furthermore, the key challenges and prospects for exploring and developing RPPOs SSEs in all‐solid‐state batteries are suggested. This review presents in detail the synthesis methods, the ion transportation mechanism, and strategies to enhance the room temperature ionic conductivity of RPPOs SSEs, providing valuable insights on enhancing their ionic conductivity and thus for their practical application in solid‐state batteries.

Abstract There are limited studies on mutation profiling for Peripheral T‐cell lymphomas (PTCL) in the Chinese population. We retrospectively analyzed the clinical and genetic landscape of 66 newly diagnosed Chinese patients. Targeted next‐generation sequencing (NGS) was performed for tissues from these patients. At least one mutation was detected in 60 (90.9%) patients, with a median number of 3 (0–7) mutations, and 32 (48.5%) cases detected with more than 4 mutations. The genes with higher mutation frequencies were TET2, RHOA, DNMT3A, IDH2, TP53, STAT3, and KMT2D respectively. When mutant genes are classified by functional group, the most prevalent mutations are related to epigenetics and signal transduction. IPI ≥2, PIT ≥2, and failure to achieve partial remission (PR) were factors for inferior progression‐free survival (PFS) and overall survival (OS). Multivariate analysis showed TP53 was an adverse factor for PFS (HR, 3.523; 95% CI, 1.262–9.835; p = 0.016), and KMT2D was an adverse factor for OS (HR, 10.097; 95% CI, 1.000–101.953; p = 0.048). Mutation profiling could help differentiate distinct types of PTCL and serve as a useful tool for determining treatment options and prognoses.

Abstract Deep penetration and downregulation of heat shock protein (HSP) expression in multimodal synergistic therapy are promising approaches for curing cancer in clinical trials. However, free small‐molecule drugs and most drug vehicles have a low delivery efficiency deep into the tumor owing to poor drug penetration and hypoxic conditions at the tumor site. In this study, the objective is to use reactive oxygen species (ROS)‐responsive supramolecular gels co‐loaded with the photosensitizer Zn(II) phthalocyanine tetrasulfonic acid (ZnPCS4) and functionalized tetrahedral DNA (TGSAs) (G@P/TGSAs) to enhance deep tissue and cell penetration and block the HSP90 pathway for chemo‐ photodynamic therapy (PDT) ‐ photothermal therapy (PTT) trimodal synergistic therapy. The (G@P/TGSAs) are injected in situ into the tumor to release ZnPCS4 and TGSAs under high ROS concentrations originating from both the tumor and PDT. TGSAs penetrate deeply into tumor tissues and augment photothermal therapy by inhibiting the HSP90 pathway. Proteomics show that HSP‐related proteins and molecular chaperones are inhibited/activated, inhibiting the HSP90 pathway. Simultaneously, the TGSA‐regulated apoptotic pathway is activated. In vivo study demonstrates efficient tumor penetration and excellent trimodal synergistic therapy (45% tumor growth inhibition).

Abstract There lacks real‐world study with a large sample size assessing olmesartan medoxomil‐amlodipine besylate (OM‐AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM‐AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM‐AML (20/5 mg) tablet were analyzed in the current prospective, single‐arm, multi‐center, real‐world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was ‐10.8 ± 0.4/‐6.6 ± 0.3 mmHg at W4 and ‐12.7 ± 0.5/‐7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home‐measured SeSBP and SeDBP decreased from W1 to W8 (both p

Background A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as an add‐on treatment to optimized lipid‐lowering therapy in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia. Methods and Results A total of 806 patients who were receiving stable and optimized lipid‐lowering therapy but did not achieve their low‐density lipoprotein cholesterol (LDL‐C) targets were enrolled and randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks, or ongericimab 300 mg or matching placebo every 4 weeks for 52 weeks. Efficacy and safety were evaluated in 802 patients who received at least 1 dose of ongericimab or placebo. The primary end point was the percentage change in LDL‐C from baseline to week 24. Our findings demonstrated that the least‐squares mean difference of percentage change in LDL‐C from baseline to week 24 was −67.7% (95% CI, −72.5% to −63.0%; P

Abstract Background Comparative investigations evaluating the efficacy of pomalidomide‐based (Pom‐based) versus daratumumab‐based (Dara‐based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real‐world studies. Methods This retrospective cohort study included 140 RRMM patients treated with Pom‐based or Dara‐based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023. Results The overall response rates (ORR) for Pom‐based (n = 48), Dara‐based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression‐free survival (PFS) was 5.7 months (95% CI: 5.0–6.5) for the Pom‐based group, 10.5 months (5.2–15.8) for the Dara‐based group, and 6.7 months (4.0–9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara‐based vs. Pom‐based, DPd vs. Pom‐based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double‐refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara‐based regimens over Pom‐based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara‐based and DPd regimens (Pom‐based 39.6% vs. Dara‐based 64.7% vs. DPd 70.8%, p = 0.009). Conclusions In real‐world settings, Pom‐based, Dara‐based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara‐based therapy yielded superior clinical response and PFS compared to Pom‐based therapy.

Abstract Transformer winding turns often consist of multiple parallel strands. The spatial position variation of each strand affects the leakage inductance of each branch, resulting in an uneven distribution of short‐circuit currents within the winding turns. And this unevenness persists even when transposition structures are implemented. Traditional methods in transformer analysis frequently overlooked the distribution characteristics of short‐circuit currents when calculating electromagnetic forces. A frequency‐domain calculation method for analysing the current distribution in winding turns was proposed, with a deviation of less than 3% compared to existing analysis methods. Two typical 110 kV transformer models were utilised to investigate the influence of uneven current distribution on the spatial distribution of electromagnetic forces. The spatial distribution of short‐circuit electromagnetic forces in low‐voltage (LV) windings exhibited significant changes, with maximum change rates of 10% and 61.2% for axial and radial electromagnetic force, respectively, in a LV winding with 4 parallel strands. The research also analysed how strand radial width and axial height affect current distribution unevenness and proposed specific design principles to mitigate these disparities in winding design. The findings offer valuable insights for selecting structural parameters and assessing short‐circuit stability during transformer design.

Abstract Accurately calculating axial electromagnetic force is essential to analyse transformer winding axial stability. Prior research has mainly focused on the effect of winding structure on static axial electromagnetic force and studying vibration by substituting the static force in a time‐varying function. However, the coupling effect between axial electromagnetic force and winding vibration has not been addressed, and no calculation method for the axial electromagnetic force that considers both winding meso‐structures and vibration coupling effects has been proposed. Previously the authors presented an electromagnetic force calculation model that considers winding structure characteristics, and an iterative algorithm for magnetic‐structure coupling calculation. Currently, the winding vibration model was first proposed and the dynamic calculation method was formulated. By applying the method to a typical 110kV transformer, the spatial‐temporal distribution of winding axial short‐circuit electromagnetic force was obtained. It was found that the peak value of the axial short‐circuit electromagnetic force of some windings appears at the second or third peak moment of the short‐circuit current, which is called as peak time shift phenomenon. Further stress analysis indicates that existing evaluation methods may overestimate the short‐circuit resistance of windings by only considering short‐circuit electromagnetic force under maximum peak of short‐circuit current.

Abstract Background The wide use of antibody‐drug conjugates (ADCs) is transforming the cancer‐treatment landscape. Understanding the treatment‐related adverse events (AEs) of ADCs is crucial for their clinical application. We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies. Methods We searched the PubMed, Embase, and Cochrane Library databases for articles published from January 2001 to October 2022. The overall profile and incidence of all‐grade and grade ≥ 3 treatment‐related AEs were the primary outcomes of the analysis. Results A total of 138 trials involving 15,473 patients were included in this study. The overall incidence of any‐grade treatment‐related AEs was 100.0% (95% confidence interval [CI]: 99.9%–100.0%; I2 = 89%) and the incidence of grade ≥ 3 treatment‐related AEs was 6.2% (95% CI: 3.0%–12.4%; I² = 99%). Conclusions This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment. ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade ≥ 3 AEs. The AE profiles and incidence differed according to cancer type, ADC type, and ADC components.

Abstract Background Malignant liver tumors seriously endanger human health. Among different therapeutic approaches, high‐frequency irreversible electroporation (H‐FIRE) is a recently emerging tumor ablation technique. The objective of this study was to evaluate the feasibility and safety of ultrasound‐guided percutaneous H‐FIRE using four electrode needles in porcine livers. Methods Twelve experimental pigs underwent percutaneous H‐FIRE ablation using a compound steep‐pulse therapeutic device. Liver tissues adjacent to the gallbladder, blood vessels, and bile ducts were selected as the ablation targets. Pigs were randomly divided into three groups: (1) immediately after ablation (N = 4), (2) 2 days after ablation (N = 4), and (3) 7 days after ablation (N = 4). Blood routine, liver and kidney function, and myocardial enzyme levels were measured before and after ablation. Ultrasound, contrast‐enhanced ultrasound (CEUS), contrast‐enhanced magnetic resonance imaging (MRI), and hematoxylin–eosin staining were performed to evaluate the ablation performance. Results Ultrasound‐guided percutaneous H‐FIRE ablations using four electrode needles were successfully performed in all 12 experimental pigs. The general conditions of the pigs, including postoperative activities and feeding behaviors, were normal, with no significant changes compared with the preoperative conditions. The imaging features of ultrasound, CEUS, and MRI demonstrated no significant changes in the gallbladder walls, bile ducts, or blood vessels close to the ablation areas. Laboratory tests showed that liver function indices and myocardial enzymes increased temporarily after H‐FIRE ablation, but decreased to normal levels at 7 days after ablation. Histopathological examinations of porcine liver specimens showed that this technique could effectively ablate the target areas without damaging the surrounding or internal vascular systems and gallbladder. Conclusions This study demonstrated the feasibility and safety of ultrasound‐guided percutaneous H‐FIRE ablation in porcine livers in vivo, and proposed a four‐needle method to optimize its clinical application.

Abstract Triple‐positive breast cancer (TPBC) poorly responds to current standard neoadjuvant therapy (trastuzumab plus pertuzumab and chemotherapy). Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib (pan‐human epidermal growth factor receptor tyrosine kinase inhibitor) plus dalpiciclib (cyclin‐dependent kinase 4/6 inhibitor) and letrozole, but the efficacy remains suboptimal. This pilot study (NCT05228951) explored adding trastuzumab to this triplet neoadjuvant regimen in patients with stage II–III TPBC. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Between February 2022 and June 2022, 12 patients were enrolled, and seven (58%; 95% confidence interval [CI], 27.7%–84.8%) patients achieved tpCR. The rate of residual cancer burden (RCB) 0–I was 75% (95% CI, 46.8%–91.1%). The objective response rate (ORR) was 92% (95% CI, 64.6%–98.5%). Mean Ki‐67 level was significantly reduced from 45.0% (95% CI, 19.5%–70.5%) at baseline to 17.2% (95% CI, 0.7%–33.7%) after neoadjuvant therapy (p = 0.03). The most common grade 3 adverse events were diarrhea (four [33%]) and decreased neutrophil count (three [25%]). No grade 4 adverse events or treatment‐related deaths occurred. This four‐drug neoadjuvant regimen shows promising pathological response with an acceptable safety profile in patients with TPBC. A randomized controlled trial (NCT05638594) of this regimen is being conducted.

Abstract Pure organic materials with persistent and efficient room‐temperature phosphorescence have recently aroused great research interest due to their vast potential in applications. One crucial design principle for such materials is to suppress as much as possible the non‐radiative decay of the triplet exciton while maintaining a moderate phosphorescent radiative rate. However, molecular engineering often exhibits similar regulation trends for the two processes. Here, we propose that the quantum interference caused by aggregation can be utilized to control the phosphorescent and non‐radiative decay channels. We systematically analyze various constructive and destructive transition pathways in aggregates with different molecular packing types and establish clear relationships between the luminescence characters and the signs of the singlet and triplet excitonic couplings. It is shown that the decay channels can be flexibly switched on or off by regulating the packing type and excitonic couplings. Most importantly, an enhanced phosphorescent decay and a completely suppressed non‐radiative decay can be simultaneously realized in the aggregate packed with inversion symmetry. This work lays the theoretical foundation for future experimental realization of quantum interference effects in phosphorescence.

Abstract Introduction Locoregional recurrent breast cancers have a poor prognosis. Little is known about the prognostic impact of immune microenvironment, and tertiary lymphoid structures (TLSs) in particular have not been reported. Thus, we aimed to characterize the immune microenvironment in locoregional recurrent breast tumors and to investigate its relationship with prognosis. Methods We retrospectively included 112 patients with locoregional recurrent breast cancer, and hematoxylin–eosin staining and immunohistochemical staining (CD3, CD4, CD8, CD19, CD38, and CD68) were performed on locoregional recurrent tumor samples. The association of immune cells and TLSs with progression‐free survival (PFS) were analyzed by survival analysis. Results We found more immune cells in the peritumor than stroma. After grouping according to estrogen receptor (ER) status, a low level of peritumoral CD3+ cells in ER+ subgroup (p = 0.015) and a low level of stromal CD68+ cells in ER− subgroup (p = 0.047) were both associated with longer PFS. TLSs were present in 68% of recurrent tumors, and CD68+ cells within TLSs were significantly associated with PFS as an independent prognostic factor (p = 0.035). TLSs and immune cells (CD3, CD38, and CD68) within TLSs were associated with longer PFS in ER− recurrent tumors (p = 0.044, p = 0.012, p = 0.050, p

The widespread dissemination of high-fidelity fake faces created by face forgery techniques has caused serious trust concerns and ethical issues in modern society. Consequently, face forgery detection has emerged as a prominent topic of research to prevent technology abuse. Although, most existing face forgery detectors demonstrate success when evaluating high-quality faces under intra-dataset scenarios, they often overfit manipulation-specific artifacts and lack robustness to postprocessing operations. In this work, we design an innovative dual-branch collaboration framework that leverages the strengths of the transformer and CNN to thoroughly dig into the multimodal forgery artifacts from both a global and local perspective. Specifically, a novel adaptive noise trace enhancement module (ANTEM) is proposed to remove high-level face content while amplifying more generalized forgery artifacts in the noise domain. Then, the transformer-based branch can track long-range noise features. Meanwhile, considering that subtle forgery artifacts could be described in the frequency domain even in a compression scenario, a multilevel frequency-aware module (MFAM) is developed and further applied to the CNN-based branch to extract complementary frequency-aware clues. Besides, we incorporate a collaboration strategy involving cross-entropy loss and single center loss to enhance the learning of more generalized representations by optimizing the fusion features of the dual branch. Extensive experiments on various benchmark datasets substantiate the superior generalization and robustness of our framework when compared to the competing approaches.

Abstract The authors conducted an observational study to explore the association between body fat composition and the risk of hyperhomocysteinemia (HHcy) and their combined effect on the risk of developing cardiovascular disease (CVD). Adults aged 18–74 years from the Northwest China Natural Population Cohort: Ningxia Project (CNC‐NX) were recruited in this study. Association between body fat composition and HHcy was evaluated by logistic regression model. Restricted cubic spline was used to find nonlinear association. The impact of the interaction between HHcy and body fat composition on CVD was evaluated using the addition interaction model and mediation effect model. In total, 16 419 participants were included in this research. Body fat percentage, visceral fat level, and abdominal fat thickness were positively associated with overall HHcy (p for trend

Abstract Background Multifocal (MF) and multicentric (MC) breast cancer cases have been increasingly diagnosed owing to the extensive use of improved preoperative breast imaging. The current tumor‐node‐metastasis staging system uses the dimension of the largest tumor and recommends reporting the pathological features of the largest tumor in MF/MC breast cancers. Aim This study aimed to explore whether the largest or aggregate dimensions of MF and MC breast cancers can better predict tumor behavior. We also attempted to study the histological and biological heterogeneities of separate foci in MF and MC breast cancers to determine whether it was necessary to examine each lesion. Methods We retrospectively analyzed 121 patients with MF/MC (103 with MF and 18 with MC) breast cancers and 484 patients with unifocal breast cancer who were treated at the First Affiliated Hospital of Nanjing Medical University. Two methods were used to record the T stage (using the dimensions of the largest lesion and aggregate dimensions of all lesions). The histological grade, immunohistochemical parameters, and molecular subtypes of the largest lesion and other lesions in MF/MC breast cancers were studied to assess intertumoral heterogeneity. Results The use of aggregate dimensions upstaged 63 patients with MF/MC breast cancers to a more advanced stage and removed the independent effect of cancer multiplicity on lymph node positivity compared with the use of the largest dimension. Mismatches were found in the pathological type (9.9%), histological grade (4.1%), and molecular subtype (8.3%) among different foci. Conclusion The tendency of MF/MC breast tumors to metastasize may be related to tumor load, which can be better predicted by the aggregate dimensions of all foci. The use of the current staging systems may require further evaluation and modification. Intertumoral heterogeneity indicates the necessity for pathological and immunohistochemical assessments of each lesion in patients with MF/MC breast cancers.

Abstract Topological transition metal dichalcogenides (TMDCs) have attracted much attention due to their potential applications in spintronics and quantum computations. In this work, the structural and electronic properties of topological TMDCs candidate ZrTe2 are systematically investigated under high pressure. A pressure‐induced Lifshitz transition is evidenced by the change of charge carrier type as well as the Fermi surface. Superconductivity is observed at around 8.3 GPa without structural phase transition. A typical dome‐shape phase diagram is obtained with the maximum Tc of 5.6 K for ZrTe2. Furthermore, the theoretical calculations suggest the presence of multiple pressure‐induced topological quantum phase transitions, which coexists with emergence of superconductivity. The results demonstrate that ZrTe2 with nontrivial topology of electronic states displays new ground states upon compression.

Abstract Spectrum resources are becoming harder to come by for wireless communications. The spectrum environment map (SEM), which depicts the electromagnetic environment's current state and future trend, is a valuable technique for managing and allocating spectrum resources. Most SEM construction approaches only take static SEMs into account and cannot forecast time‐domain changes and trends of SEMs in dynamic scenes. In this paper, a brand‐new temporal SEM prediction method for the high dynamic spectrum environment is proposed. This method is based on knowledge of radiation source and the optical flow driven by propagation channel models. First, a novel radiation source localization strategy is designed to obtain the radiation source movement information. Then, the optical flow field of the available SEMs is combined with the information regarding radiation source movement. In order to forecast future SEMs, a propagation model driven reconstruction technique is developed. Simulation findings demonstrate how well the suggested strategy is tailored to capture the spatiotemporal correlation of SEMs. This technique performs better than the state‐of‐the‐art in terms of single‐ and multiple‐step SEM predictions.

Abstract Rationally constructing atom‐precise active sites is highly important to promote their catalytic performance but still challenging. Herein, this work designs and constructs ZSM‐5 supported Cu and Ag dual single atoms as a proof‐of‐concept catalyst (Ag1−Cu1/ZSM‐5 hetero‐SAC (single‐atom catalyst)) to boost direct oxidation of methane (DOM) by H2O2. The Ag1−Cu1/ZSM‐5 hetero‐SAC synthesized via a modified co‐adsorption strategy yields a methanol productivity of 20,115 µmol gcat−1 with 81% selectivity at 70 °C within 30 min, which surpasses most of the state‐of‐the‐art noble metal catalysts. The characterization results prove that the synergistic interaction between silver and copper facilitates the formation of highly reactive surface hydroxyl species to activate the C−H bond as well as the activity, selectivity, and stability of DOM compared with SACs, which is the key to the enhanced catalytic performance. This work believes the atomic‐level design strategy on dual‐single‐atom active sites should pave the way to designing advanced catalysts for methane conversion.

Abstract The authors propose and experimentally demonstrate an on‐chip all‐optical multicasting (AOM) for 40 Gbit/s mode‐division‐multiplexed quadrature phase‐shift keying (MDM‐QPSK) signals based on a parallel dispersion‐engineered multimode non‐linear silicon waveguide. Five dual‐mode multicast wavelengths are successfully obtained on the generate idlers, and the power penalties of all the multicast channels are less than 1.1 dB at the bit error rate (BER) of 3.8 × 10−3. The dual‐mode AOM scheme has the potential to promote the ability of optical cross‐connect in practical hybrid multiplexed networks including MDM channels.

Objectives Sitting is a common weight‐bearing posture, like standing, but there still lacks enough understanding of sagittal alignment in sitting position for patients after lumbar fusion. This study aimed to investigate the accommodation of fixed spine from standing to sitting position and its influence on unfused segments. Methods Sixty‐two patients after lumbar fusion (test group) and 40 healthy volunteers (control group) were recruited in this research. All subjects underwent lateral radiographs of entire spine in the standing and sitting positions. The spinopelvic parameters including sagittal vertical axis (SVA), T1 pelvic angle (TPA), lumbar lordosis (LL), thoracic kyphosis (TK), and pelvic tilt (PT) were measured. The changes in parameters of patients between two positions were compared with control group, and patients were divided in different groups based on fusion level and their parameters were compared. Results When changing from standing to sitting positions, a forward‐moving SVA and TPA were observed in both patients and control groups, accompanied by the decrease in LL, TK and increase in PT, but the changes of patients were smaller in TPA, LL, and TK (6.5° ± 7.2° vs 9.7° ± 6.0°, 7.7° ± 8.3° vs 13.6° ± 8.5°, 2.2° ± 6.5° vs 5.4° ± 5.1°, respectively, p

Abstract To reveal the correlation of dynamic serum tumor markers (STMs) and molecular features of epidermal growth factor receptor‐mutated (EGFR‐mutated) lung cancer during targeted therapy, we retrospectively reviewed 303 lung cancer patients who underwent dynamic STM tests [neuron‐specific enolase (NSE), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), the soluble fragment of cytokeratin 19 (CYFRA21‐1), and squamous cell carcinoma antigen (SCC)] and circulating tumor DNA (ctDNA) testing with a panel covering 168 genes. At baseline, patients with EGFR mutation trended to have abnormal CEA, abnormal CA153, and normal SCC levels. Additionally, patients with Thr790Met (T790M) mutation were more likely to have abnormal CEA levels than patients without T790M mutation. Among patients with secondary resistance to EGFR tyrosine kinase inhibitors (TKI), the dynamic STMs showed a descending trend in the responsive stage and a rising trend in the resistant stage. However, the changing slopes differed between T790M subgroup and the non‐T790M subgroup in individual STMs. Our study demonstrated that the combination of baseline levels and variations of STMs (including the responsive stage and resistant stage) can be suggestive of secondary EGFR‐T790M mutation [area under the curve (AUC) = 0.897] and that changing trends of STMs (within 8 weeks after initiating the TKI therapy) can be potential predictors for the clearance of EGFR ctDNA [AUC = 0.871]. In conclusion, dynamic monitoring STMs can help to predict the molecular features of EGFR‐mutated lung cancer during targeted therapy.

Abstract Background and aims The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single‐cell level is rare due to the need for fresh and high‐quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. Methods Five paired samples of intramucosal ESCC, para‐ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA‐seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. Results A total of 164 715 cells were profiled. Epithelial cells exhibited high intra‐tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEXs, Tregs and PD1+CD4+T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand–receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK–NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. Conclusion This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies.

Abstract Extracellular vesicles (EVs) are cell‐derived membrane‐enclosed structures that deliver biomolecules for intercellular communication. Developing visualization methods to elucidate the spatiotemporal dynamics of EVs’ behaviors will facilitate their understanding and translation. With a quantum dot (QD) labeling strategy, a single particle tracking (SPT) platform is proposed here for dissecting the dynamic behaviors of EVs. The interplays between tumor cell‐derived small EVs (T‐sEVs) and endothelial cells (ECs) are specifically investigated based on this platform. It is revealed that, following a clathrin‐mediated endocytosis by ECs, T‐sEVs are transported to the perinuclear region in a typical three‐stage pattern. Importantly, T‐sEVs frequently interact with and finally enter lysosomes, followed by quick release of their carried miRNAs. This study, for the first time, reports the entire process and detailed dynamics of T‐sEV transportation and cargo‐release in ECs, leading to better understanding of their proangiogenic functions. Additionally, the QD‐based SPT technique will help uncover more secrets of sEV‐mediated cell–cell communication.

This study investigates the seismic behavior of the T-shaped concrete-filled steel tubular (CFST) column to steel beam joints, aimed at expanding their applicability in areas with high-seismic fortification intensity. A construction form of T-shaped CFST column to steel beam joint with side plates is presented. The variables studied in these experiments include the side plate length, the axial compression ratio, the presence of side plates, and the presence of binding bars. The force mechanism, failure modes, load–displacement curves, strength, stiffness, ductility, and energy dissipation capacity of seven specimens were evaluated under low-cycle reciprocating load. The experimental results demonstrate that the joints of side plates show a full hysteresis curve, with the ductility coefficient ranging from 1.67 to 2.49, and the equivalent viscous damping coefficient between 0.147 and 0.234. The joint panel zone displays strong deformation and energy dissipation capacity. The inclusion of side plates and binding bars improves the seismic behavior of the joint. The setting of side plates enables the formation of a plastic hinge on the steel beam, creating a beam hinge failure mechanism and satisfying the seismic design principle of “strong column and weak beam, strong joint and weak member” as required by the building structures.

In bearing capacity testing of prestressed concrete pipe piles, grouting material is filled up to the bottom of the pipe pile, which is equipped with a finishing rolled rebar. The reaction force of the reaction beam is transferred to the anchor pile through the bonding force between the finishing rolled rebar and grouting material. Therefore, investigating the bonding properties between the finishing rolled rebar and grouting material is essential to remove barriers to the application of the anchor pile method in bearing capacity testing of the prestressed concrete pipe pile. In this study, the bonding properties of 11 groups of specimens were studied through pull-out tests, and the effects of the cover thickness, diameter, and anchorage length of reinforcement on the bond strength between finishing rolled rebar and grouting material as well as on the bond stress-slip curve were explored. The test results showed that the bond stress-slip curve between finishing rolled rebar and grouting material can be divided into two stages, i.e., slip stage and splitting failure stage. In the slip stage, a linear relationship exists between bond stress and slip amount, and microcracks appear in the grouting material around the finishing rolled rebar. In the splitting failure stage, the slip amount increases rapidly under uplift load. Finally, the grouting material around the finishing rolled rebar forms a failure zone, and splitting failure occurs. The bonding capacity and bond strength between finishing rolled rebar and grouting material increase with the increasing cover thickness of the rebar. The bond strength is the maximum for a relative cover thickness of 3.0, and the difference between the maximum and minimum values is more than 9%. The bonding capacity between rebar and grouting material increases slightly with the increasing rebar diameter, but the bond strength decreases with the diameter, and the difference between the maximum and minimum bond strengths is more than 21%. As the contact area between finishing rolled rebar and grouting material increases, the bonding capacity between them increases with the increasing anchorage length of the rebar. However, the bond strength first increases, then decreases, and finally stabilizes with the increasing anchorage length, and the difference between the maximum and minimum bond strengths exceeds 14.64%.

In view of the poor accuracy and unsatisfactory effect of shrinkage compensation for concrete-filled steel tubular structures of large cross-sea bridge (CSTS-LCSB), a new shrinkage compensation technology for CSTS-LCSB is proposed. The shrinkage mechanism of CSTS-LCSB is analyzed, including plastic shrinkage, dry shrinkage, autogenous shrinkage, and carbonation shrinkage. The proportion of dry shrinkage and autogenous shrinkage in ordinary concrete and high-strength concrete is determined. The CSTS-LCSB has different shrinkage forms in different environments, and the shrinkage strain state of CSTS-LCSB in different environments is calculated according to the difference. The shrinkage area of the concrete structure is determined, and the expansion agent is used to compensate for the shrinkage area of CSTS-LCSB. The experimental results show that the proposed compensation technology has a good effect on shrinkage compensation and has certain feasibility.

Abstract Sarcopenia, characterized by loss of skeletal muscle mass, quality, and strength, has become a common hallmark of ageing and many chronic diseases. Diabetes mellitus patients have a higher prevalence of sarcopenia, which greatly aggravates the metabolic disturbance and compromises treatment response. Preclinical and clinical studies have shown differential impacts of anti‐diabetic drugs on skeletal muscle mass, strength, and performance, highlighting the importance of rational therapeutic regimen from the perspective of sarcopenia risk. In this review, we provide an update on the regulation of muscle mass and quality by major anti‐diabetic drugs, focusing primarily on emerging data from clinical studies. We also discuss the underlying mechanisms and clinical implications for optimal selection of anti‐diabetic drugs to reduce the risk of sarcopenia. In view of the lifelong use of anti‐diabetic drugs, we propose that a better understanding of the sarcopenia risk and interventional strategies is worthy of attention in future studies.

Abstract Objective Immunoglobulin G4‐related disease (IgG4‐RD) is a systemic immune‐mediated fibroinflammatory condition. Previous studies have indicated relationships between malignancy and autoimmunity. This retrospective cohort study aimed to determine IgG4‐RD incidence and clinical features in patients with a family history of malignancy. Methods To analyze the relationship between IgG4‐RD and family history of malignancy, we reviewed IgG4‐RD patients with a family history of malignancy diagnosed in various departments in West China Hospital, Sichuan University from December 2012 to September 2019. Clinical data and laboratory features were compared between IgG4‐RD patients with and without a family history of malignancy. Results Among 168 enrolled patients with IgG4‐RD, 22 (13.1%) had a family history of malignancy. The most frequently involved system in family members with malignancy was the digestive system (38.5%). Among patients with a family history of malignancy, the most frequently involved organs in IgG4‐RD were the pancreas (31.9%) and lymph nodes (31.9%). Age at symptom onset was older in IgG4‐RD patients with a family history of malignancy than in patients without a family history of malignancy (50–59 years: 36.3% vs. 16.4%, p = 0.0393). Hemoglobin (p = 0.0172) and albumin (p = 0.0247) levels were higher and globulin (p = 0.0232) levels were lower in patients with a family history of malignancy. Conclusions Our findings suggest that a family history of malignancy may be associated with IgG4‐RD development. We hypothesize that genetic susceptibility may be involved in the pathogenesis of IgG4‐RD.

Abstract This article discusses the exponential synchronisation problem for multiple neural networks with time‐varying delay and a more general non‐Laplacian coupling matrix is considered. To reduce the redundant communication, two event‐based time‐varying delay hybrid impulsive control schemes are proposed with static event‐triggered condition and dynamic event‐triggered condition. These novel control schemes neatly combine the event‐triggered coupling strategy with the time‐varying delay hybrid impulsive control, where the impulsive instant is only determined by the specified event‐triggered condition. Moreover, a delay impulsive differential inequality is established to discuss the synchronisation problem for controlled multiple neural networks. By using Stolz's theorem and introducing the average event‐triggered delay impulsive gain, some less conservative sufficient conditions are derived to assure the stability of the time‐varying delay multiple neural networks. Furthermore, the Zeno behaviour can be eliminated effectively and the consumption of the computing resources can be reduced. Finally, some examples are given to verify the superiority of the results. First, a static event‐triggered time‐varying delay hybrid impulsive control scheme was proposed to lessen the communication burden. Then, a time‐varying delay impulsive differential inequality was established to guarantee the synchronisation of multiple neural networks. Moreover, the authors also discussed the issue that continuously triggering and sampling can be excluded.

Abstract We consider leveraging the joint potential of non‐orthogonal multiple access (NOMA) and traffic offloading to benefit cell‐edge users in multi‐cell scenarios. We formulate the edge‐driven throughput maximisation problem where both the offloading decision and resource allocation are to be optimised, accounting for the impact of the inter‐cell interference on the decoding order in NOMA. The inter‐cell interference is not given constants as it is influenced by resource allocation. Therefore the non‐orthogonal multiple access (NOMA) decoding order is not known a priori. We explore the problem by decomposing it into two subproblems. By analysis of structural properties, we derive algorithm modules which interact iteratively for reciprocity, forming the overall algorithm. Numerical results show that the proposed scheme considerably improves the cell‐edge throughput, compared with the conventional scheme of orthogonal multiple access without traffic offloading.

Abstract Background The biological function of mesenchymal stem‐like cells (MSLCs), a type of stromal cells, in the regulation of the tumour microenvironment is unclear. Here, we investigated the molecular mechanisms underlying extracellular matrix (ECM) remodelling and crosstalk between MSLCs and glioblastomas (GBMs) in tumour progression. Methods In vitro and in vivo co‐culture systems were used to analyze ECM remodelling and GBM infiltration. In addition, clinical databases, samples from patients with GBM and a xenografted mouse model of GBM were used. Results Previous studies have shown that the survival of patients with GBM from whom MSLCs could be isolated is substantially shorter than that of patients from whom MSLCs could not be isolated. Therefore, we determined the correlation between changes in ECM‐related gene expression in MSLC‐isolatable patients with that in MSLC non‐isolatable patients using gene set enrichment analysis (GSEA). We found that lysyl oxidase (LOX) and COL1A1 expressions increased in MSLCs via GBM‐derived clusters of differentiation 40 ligand (CD40L). Mechanistically, MSLCs are reprogrammed by the CD40L/CD40/NFκB2 signalling axis to build a tumour infiltrative microenvironment involving collagen crosslinking. Importantly, blocking of CD40L by a neutralizing antibody‐suppressed LOX expression and ECM remodelling, decreasing GBM infiltration in mouse xenograft models. Clinically, high expression of CD40L, clusters of differentiation 40 (CD40) and LOX correlated with poor survival in patients with glioma. This indicated that GBM‐educated MSLCs promote GBM infiltration via ECM remodelling in the tumour microenvironment. Conclusion Our findings provide mechanistic insights into the pro‐infiltrative tumour microenvironment produced by GBM‐educated MSLCs and highlight a potential therapeutic target that can be used for suppressing GBM infiltration.

Abstract Minimally invasive thermal therapies have been attempted in the treatment of breast cancer, and the immune response induced by these therapies has not been fully reported. A clinical trial is performed to determine the effect of microwave ablation (MWA) in the treatment of early‐stage breast cancer. The authors perform single‐cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) from six patients before and after ablation. NK and CD8+T cells are activated by MWA of breast cancer, with the increased inhibitory signature of CD8+T cells but not dysfunctional. Enhanced co‐stimulatory signature of CD4+ T cells is observed and increased frequency of ICOS+CD4+ T cells after MWA is confirmed by flow cytometric analysis. After ablation, T‐cell clones expand with increased T‐cell receptor diversities. Activated antigen receptor‐mediated signaling pathways are found in B cells. Enhanced interactions between B cells and CD4+ T cells are found, indicating that B cells are important antigen‐presenting cells that initiate CD4+T cells in MWA‐induced immune response. Blockade of CTLA‐4 or PD‐1 of post‐MWA PBMCs show higher T‐cell activity than that of pre‐MWA PBMCs. This study provide global characteristics of MWA‐induced systemic immune response and pave a way for the identification of potential targets to improve the immune response.

Roadway maintenance of the gob-side entry driving with narrow pillars is a key issue that needs to be considered in underground mining. In this paper, a thick-anchored dual-layer locking (TADL) supporting technique is proposed, in which, the flexible bolt and the cable are used as the main bodies of the foundation supporting layer and the deep reinforcement layer, respectively. In the instantaneous deformation stage after excavation, TADL is applied to form a thick-anchored bearing structure in time, aiming to achieve the following effects: (1) prevent the delamination of the roadway at the initial stage of excavation, (2) avoid the reduction of the bearing capacity of the surrounding rock structure, and (3) effectively control the plastic zone development and surrounding rock deformation of roof strata. Finally, the mining conditions of gob-side entry driving with narrow pillars are selected for engineering application and verification. The results of numerical simulation and field industrial tests show that the TADL support technique can effectively control the deformation of surrounding rock and drive away tensile stress. Compared with the original support scheme, the roof displacement of the roadway is significantly reduced by more than 16% after TADL support. This study provides a reference for the stability control of roadway roofs under similar conditions.

Accurate determinations of water (H2O) content in natural gases especially in the methane (CH4) phase are highly important for chemical engineers dealing with natural gas processes. To this end, development of a high performance model is necessary. Due to importance of the solubility of methane in the aqueous solutions for natural gas industries, two novel models based on the Decision Tree (DT) and Adaptive Neuro-Fuzzy Interference System (ANFIS) have been employed. To this end, a total number of 204 real methane solubility points in aqueous solution containing NaCl under different pressure and temperature conditions have been gathered. The comparisons between predicted solubility values and experimental data points have been conducted in visual and mathematical approaches. The R2 values of 1 for training and testing phases express the great ability of proposed models in calculation of methane solubility in pure water systems.

There is a “bottleneck effect” in the extraction process of ordinary boreholes. It is crucial to enhance the permeability of the boreholes. In this paper, a set of ultra-high-pressure water jet-based drilling and slotting integrated equipment was designed and applied, and the ultra-high-pressure safeguarding technology of several key components has been studied. Finally, the gas drainage effect of slotted boreholes and ordinary boreholes was investigated through field tests. The test results showed that after using ultra-high-pressure hydraulic slotting, the average drainage concentration of slotted boreholes is 1.49 times that of the ordinary boreholes. The average extraction scalar volume of slotted drilling is 3.02 times that of ordinary boreholes. Under the condition of original content of 12 m3/t, the extraction radii of slotted boreholes in 3 months and 6 months are 3.76 m and 4.76 m, respectively. The effective radius of the slotted boreholes is 1.76 times that of the ordinary boreholes, which indicate that the ultra-high-pressure hydraulic slotting technology can effectively relieve the pressure and increase the permeability of the soft coal seam.

Root resorption is a common dental challenge that can lead to tooth loosening or even tooth loss. Among the cells involved in root resorption, cementoblasts are responsible for laying down the cementum, while macrophages with different phenotypes have also been shown to have bidirectional effects on root resorption. However, the relationship between macrophages and cementoblasts remains largely unknown. In this study, we examined the effect of macrophages with different polarization phenotypes on the mineralization of cementoblasts. Using the transwell coculture system and a conditioned medium-based coculture system, we found that compared with M0 (unpolarized macrophages), M1-polarized macrophages attenuated cementoblast mineralization, while M2-polarized macrophages enhanced cementoblast mineralization. Furthermore, by extracting M0/M1/M2 macrophage exosomes and examining their effects on the mineralization of cementoblasts, we found that the effects of macrophages on cementoblast mineralization were, at least partially, exerted by exosomes. Moreover, in vivo studies also indicated that an increased M1/M2 ratio could suppress cementoblast mineralization and bring about root resorption. During mechanical force-induced orthodontic tooth movement (OTM), root resorption was evident on the compression side of periodontal tissue, and a higher M1/M2 ratio and weaker cementoblast mineralization were observed on the compression side than on the tension side. We also used localized lipopolysaccharide (LPS) injection to increase the M1/M2 ratio around the roots of maxillary molars, where root resorption and decreased cementoblast mineralization were also observed. Furthermore, when we injected the exosomes from M0 and M1- and M2-polarized macrophages into mice, it was observed that the cementoblast mineralization was attenuated in the group injected with M1-polarized macrophage exosomes, while it was augmented in the group injected with M2-polarized macrophage exosomes.

The platform inertial-stellar composite guidance is a composite guidance method supplemented by stellar correction on the basis of inertial navigation, which can effectively improve the accuracy of responsive launch vehicles. In order to solve the problem of rapid determining the optimal navigation star in the system, this paper proposes an algorithm based on the equivalent information compression theory. At first, this paper explains why the single-star scheme can achieve the same accuracy as the dual-star scheme. At the same time, the analytical expression of the optimal navigation star with significant initial error is derived. In addition, the available optimal navigation star determination strategy is also designed according to the arrow-borne navigation star database. The proposed algorithm is evaluated by two representative responsive launch vehicle trajectory simulations. The simulation results demonstrate that the proposed algorithm can determine the optimal navigation star quickly, which greatly shorten the preparation time before the rapid launch of vehicles and improve the composite guidance accuracy.

Abstract Despite aggressive clinical treatment, recurrence of glioblastoma multiforme (GBM) is unavoidable, and the clinical outcome is still poor. A convincing explanation is the phenotypic transition of GBM cells upon aggressive treatment such as radiotherapy. However, the microenvironmental factors contributing to GBM recurrence after treatment remain unexplored. Here, it is shown that radiation‐treated GBM cells produce soluble intercellular adhesion molecule‐1 (sICAM‐1) which stimulates the infiltration of macrophages, consequently enriching the tumor microenvironment with inflammatory macrophages. Acting as a paracrine factor, tumor‐derived sICAM‐1 induces macrophages to secrete wingless‐type MMTV integration site family, member 3A (WNT3A), which promotes a mesenchymal shift of GBM cells. In addition, blockade of either sICAM‐1 or WNT3A diminishes the harmful effect of radiation on tumor progression. Collectively, the findings indicate that cellular crosstalk between GBM and macrophage through sICAM‐1‐WNT3A oncogenic route is involved in the mesenchymal shift of GBM cells after radiation, and suggest that radiotherapy combined with sICAM‐1 targeted inhibition would improve the clinical outcome of GBM patients.

Abstract Honey is thought to act against microbes and regulates microbiota balance, and this is mainly attributed to the enzymatic production of hydrogen peroxide, high osmolarity, and nonperoxidase factors, for example, lysozyme and botanical sources of nectar, while the effect of honey's probiotic is recently considered. The study of honey as source of beneficial microbes is understudied. The purpose of this study was to screen for the beneficial microorganisms in honey with antagonistic property against important pathogens and the mechanism of antimicrobial activity and thus play a beneficial role as probiotics. The results showed that one out of the fourteen bacterial isolates had antimicrobial activity and was identified as Bacillus Sp. A2 by 16S rRNA sequence and morphology. Antimicrobial activity of the isolate against C. albicans, E. coli, and S. aureus was confirmed by Agar well diffusion and liquid coculture assays, and the propagation of those microbes was significantly inhibited after treatment with the isolate Bacillus sp. A2 (p

Abstract Climate change poses a serious threat to biodiversity. Predicting the effects of climate change on the distribution of a species' habitat can help humans address the potential threats which may change the scope and distribution of species. Pterocarya stenoptera is a common fast‐growing tree species often used in the ecological restoration of riverbanks and alpine forests in central and eastern China. Until now, the characteristics of the distribution of this species' habitat are poorly known as are the environmental factors that influence its preferred habitat. In the present study, the Maximum Entropy Modeling (Maxent) algorithm and the Genetic Algorithm for Ruleset Production (GARP) were used to establish the models for the potential distribution of this species by selecting 236 sites with known occurrences and 14 environmental variables. The results indicate that both models have good predictive power. Minimum temperature of coldest month (Bio6), mean temperature of warmest quarter (Bio10), annual precipitation (Bio12), and precipitation of driest month (Bio14) were important environmental variables influencing the prediction of the Maxent model. According to the models, the temperate and subtropical regions of eastern China had high environmental suitability for this species, where the species had been recorded. Under each climate change scenario, climatic suitability of the existing range of this species increased, and its climatic niche expanded geographically to the north and higher elevation. GARP predicted a more conservative expansion. The projected spatial and temporal patterns of P. stenoptera can provide reference for the development of forest management and protection strategies.

Abstract The aim of present study was to develop folic acid (FA)‐modified nonionic surfactant vesicles (NISVs, niosomes) as carrier systems for targeted delivery of gambogenic acid (GNA). The FA‐GNA‐NISVs exhibited a mean particle size of 180.77 ± 2.41 nm with a narrow poly dispersion index of 0.147 ± 0.08 determined by dynamic light scattering. Transmission electron microscopy also revealed that the FA‐GNA‐NISVs were spherical with double‐layer structure. Entrapment efficiency (EE%) and zeta potential of the optimal FA‐GNA‐NISVs were 87.84 ± 1.06% and −37.33 ± 0.33 mV, respectively. Differential scanning calorimetry demonstrated that the GNA was in a molecular or amorphous state inside the FA‐NISVs in vitro release profiles suggested that FA‐GNA‐NISVs could release GNA at a sustained manner, and less than 60% of GNA was released from the FA‐NISVs within 12 hours of dialysis. in vivo pharmacokinetic results illustrated that FA‐GNA‐NISVs had considerably higher Cmax, area under curve (AUC0 − t) and accumulation in lung. The cell proliferation study shown that the FA‐GNA‐NISVs significantly enhanced the in vitro cytotoxicity against A549 cells. Flow cytometry and fluorescence microscopy further demonstrated that the FA‐GNA‐NISVs increased apoptosis compared with nonmodified GNA‐NISVs and free GNA. Moreover, FA‐GNA‐NISVs induced A549 cell apoptosis in a dose‐dependent manner. In addition, cellular uptake assays showed a higher uptake of FA‐GNA‐NISVs than GNA‐NISVs as well as free GNA. Taken together, it could be concluded that FA‐GNA‐NISVs were proposed as a novel targeting carriers for efficient delivering of GNA to cancers cells.

Abstract A low‐profile metasurface antenna with circularly polarized radiation and tailored anisotropic reflection is proposed in this letter. The metasurface antenna composed of excitation structure (microstrip line with coupling slot) and a metasurface layer. The metasurface functions for two goals, generating circularly polarized wave for radiation and tailoring reflection phase for scattering, respectively. The overall structure of the metasurface antenna is compact with a dimension of 0.67λ × 0.67λ × 0.05λ at 5 GHz. Numerical and measured results confirm that the metasurface antenna exhibits 11.1% −10 dB S11 bandwidth from 4.68 to 5.23 GHz, 10.8% 3 dB axial ratio bandwidth from 4.782 to 5.37 GHz and a maximum gain of 6.83 dBic. Besides, the metasurface antenna achieves anti‐phase reflection under orthogonal polarized incident waves at around 5 GHz. To demonstrate a potential application, 16 identical metasurface antennas are put in a 4 × 4 array. The metasurface antenna array achieves directive circularly polarized radiation with a maximum gain of 15 dBic. On the other hand, when under normal illumination, the scattering field of metasurface antenna array is redistributed due to phase cancelation, so that the backward radar cross section of the array is significantly reduced, which is applicable for military platform.

Background The classification of large cell neuroendocrine carcinoma (LCNEC) has generated considerable debate and has been revised since its recognition as a separate entity. Although it shares clinical features with small cell lung carcinoma (SCLC) and was classified with SCLC in the 2015 World Health Organization classification system, numerous studies have revealed inferior treatment outcomes of LCNEC when it was treated as SCLC. Because the incidence of LCNEC is rare, its mutational landscape has not been comprehensively interrogated. Methods We performed capture‐based ultra‐deep targeted sequencing on tumor samples of LCNEC, large cell carcinoma (LCC), and SCLC to elucidate its biological relationship with these subtypes and to identify potentially targetable molecular alterations. Results Our data revealed a molecular signature, consisting of RUNX1, ERBB4, BRCA1, and EPHA3, that is distinctively mutated in LCNEC. A majority (60%) of LCNEC patients harbored copy number variations (CNVs). Interestingly, there were no common CNVs shared among the three subtypes: NFкBIA amplification was shared between LCNEC and LCC, while AKT2 amplification was shared between LCNEC and SCLC. Furthermore, genetic alterations in the PI3K/AKT/mTOR pathway were enriched in all three subtypes. Conclusion Despite the histological and/or morphological similarities among LCNEC, LCC, and SCLC, our data revealed a molecular signature, consisting of RUNX1, ERBB4, BRCA1, and EPHA3, that is distinctively mutated in LCNEC, which has the potential to be used as a panel of biomarkers to distinguish LCNEC from a molecular perspective. Furthermore, the molecular distinction among the three subtypes can also be reflected from CNV events.

Abstract Background Biotinidase deficiency (OMIM 253260) is an autosomal recessively inherited disorder affecting about 1/60,000 people worldwide. The absence or deficiency of biotinidase impairs free biotin recycling and affects biotin‐dependent carboxylase functions. Methods A Chinese patient with spontaneous recurrent epilepsy, an eczema‐like rash, hair loss, hypotonia, and hearing loss began at three months of age. Her biotinidase activity was 1.0 nmol/ml/min, 9.5% of the mean control activity, which confirmed profound biotinidase deficiency. Results Compound heterozygous for c.250‐1G > C and c.878dupT variants in the BTD gene were identified in this patient. These two variants were novel and absent in the population matched controls and any databases. Conclusions This study expanded the mutation spectrum of alterations of the BTD gene. Our patient also emphasized the critical role of biotinidase activity measurement combined with mutation analysis in early diagnosis of biotinidase deficiency.

Abstract Resting‐state functional connectivity is an important and widely used measure of individual and group differences. Yet, extant statistical methods are limited to linking covariates with variations in functional connectivity across subjects, especially at the voxel‐wise level of the whole brain. This paper introduces a modeling approach that regresses whole‐brain functional connectivity on covariates. Our approach is a mesoscale approach that enables identification of brain subnetworks. These subnetworks are composite of spatially independent components discovered by a dimension reduction approach (such as whole‐brain group ICA) and covariate‐related projections determined by the covariate‐assisted principal regression, a recently introduced covariance matrix regression method. We demonstrate the efficacy of this approach using a resting‐state fMRI dataset of a medium‐sized cohort of subjects obtained from the Human Connectome Project. The results suggest that the approach may improve statistical power in detecting interaction effects of gender and alcohol on whole‐brain functional connectivity, and in identifying the brain areas contributing significantly to the covariate‐related differences in functional connectivity.