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Abstract Aims We aim to explore the associations between serum tyrosine (Tyr) to threonine (Thr) ratio and chronic heart failure (HF) with reduced or mildly reduced ejection fraction (EF) (HFrEF or HFmrEF). Methods and results The study recruited 418 subjects (77.5% males, mean age 65.2 ± 12.5 years), including 318 HF subjects (HFrEF or HFmrEF) and 100 cardiovascular subjects without acute or chronic HF [including heart failure with preserved ejection fraction (HFpEF)] as controls. Serum levels of 21 kinds of amino acids (AAs) were measured by mass spectrometry. Logistic regression analysis was conducted to measuring the association between the AAs levels and the presence of HF. Event‐free survival was determined by Kaplan–Meier curves and differences in survival were assessed using log‐rank tests. Cox regression analysis was used to assess the prognostic value of AAs in HF. Receiver‐operating characteristic (ROC) curve was performed to further confirm regression analysis. Along with the control, HFmrEF, and HFrEF subjects, serum tyrosine (Tyr) gradually increased (64.43 ± 15.28 μmol/L vs. 71.79 ± 18.74 μmol/L vs. 77.32 ± 25.90 μmol/L, P

Abstract Aims Acute myocardial infarction (MI) is a significant contributor to death in individuals diagnosed with coronary heart disease on a worldwide level. The specific mechanism by which circRbms1 contributes to the damage caused by myocardial ischaemia–reperfusion (I/R) is not well understood. The primary aim of this study was to examine the role of circRbms1 and its associated mechanisms in the setting of I/R injury. Methods and results An in vivo MI mice model and an in vitro MI cell model was established. The expression levels were detected using quantitative real‐time PCR (qRT‐PCR) and western blot. Cellular proliferation, apoptosis, pyroptosis, and autophagy were detected by immunostaining, immunohistochemistry, western blot, and transmission electron microscopy (TEM). Dual‐luciferase reporter assay, RNA pull‐down assay, and RIP assay were performed to validate the molecular interactions. CircRbms1 was up‐regulated in A/R‐induced HCMs and acted as a sponge for miR‐142‐3p, thereby targeting MST1. CircRbms1 could improve stability of MST1 by recruiting IGF2BP2 (all P

Abstract Background Pulmonary fibrosis (PF) is a common clinically critical disease characterized by high morbidity and high mortality. Forsythiaside A (FA) is a phenylethanol glycoside component in Forsythia suspensa, which has anti‐inflammatory, antioxidant, and antiviral activities. However, the effects of FA on bleomycin (BLM)‐induced PF are unclear. Purpose The present study explored the role of FA in the amelioration of oxidative stress and apoptosis in BLM‐induced PF as well as the possible underlying mechanisms, in vivo and in vitro. Methods Network pharmacology was used to collect the effects of FA on BLM‐induced PF. Subsequently, further observation of the effects of FA on mice with PF by pulmonary pathological changes, transmission electron microscopy, real‐time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. An in vitro model was constructed by inducing A549 with transforming growth factor beta‐1 (TGF‐β1) to observe the effect of FA on epithelial cell apoptosis. Results Network pharmacology predicted signaling pathways such as IL‐17 signaling pathway and Relaxin signaling pathway. The results of in vivo studies showed that FA ameliorated BLM‐induced PF through inhibition of fibrosis, modulation of apoptosis, and oxidative stress. In addition, FA promoted TGF‐β1‐induced apoptosis in A549 cells. Conclusions The results of our study suggested that FA could protect mice against BLM‐induced PF by regulating oxidative stress and apoptosis as well as the Epithelial mesenchymal transition pathway.

Abstract Triple‐negative breast cancer (TNBC) poses a challenging prognosis due to early metastasis driven by anoikis resistance. Identifying crucial regulators to overcome this resistance is vital for improving patient outcomes. In this study, a genome‐wide CRISPR/Cas9 knockout screen in TNBC cells has identified tyrosine‐protein phosphatase nonreceptor type 14 (PTPN14) as a key regulator of anoikis resistance. PTPN14 expression has shown a progressive decrease from normal breast tissue to metastatic tumors. Overexpressing PTPN14 has induced anoikis and inhibited cell proliferation in TNBC cells, while normal human breast cells are unaffected. Mechanistically, PTPN14 is identified as a key factor in dephosphorylating breast cancer antiestrogen resistance 3, a novel substrate, leading to the subsequent inhibition of PI3K/AKT and ERK signaling pathways. Local delivery of in vitro transcribed PTPN14 mRNA encapsulated by lipid nanoparticles in a TNBC mouse model has effectively inhibited tumor growth and metastasis, prolonging survival. The study underscores PTPN14 as a potential therapeutic target for metastatic TNBC, with the therapeutic strategy based on mRNA expression of PTPN14 demonstrating clinical application prospects in alleviating the burden of both primary tumors and metastatic disease.

Abstract By modulating subwavelength structures and integrating functional materials, 2D artificial microstructures (2D AMs), including heterostructures, superlattices, metasurfaces and microcavities, offer a powerful platform for significant manipulation of light fields and functions. These structures hold great promise in high‐performance and highly integrated optoelectronic devices. However, a comprehensive summary of 2D AMs remains elusive for photonics and optoelectronics. This review focuses on the latest breakthroughs in 2D AM devices, categorized into electronic devices, photonic devices, and optoelectronic devices. The control of electronic and optical properties through tuning twisted angles is discussed. Some typical strategies that enhance light‐matter interactions are introduced, covering the integration of 2D materials with external photonic structures and intrinsic polaritonic resonances. Additionally, the influences of external stimuli, such as vertical electric fields, enhanced optical fields and plasmonic confinements, on optoelectronic properties is analysed. The integrations of these devices are also thoroughly addressed. Challenges and future perspectives are summarized to stimulate research and development of 2D AMs for future photonics and optoelectronics.

Abstract Background and objectives To analyze oncological and functional results of transoral minimally invasive surgery (TMIS) for supraglottic laryngeal carcinoma (SGLC), and investigate independent prognostic factors. Methods Seventy SGLC patients treated with TMIS were included. The overall survival (OS), recurrence‐free survival (RFS), and postoperative functions were analyzed. Results Sixty‐two patients were early‐stage (Tis, T1, and T2) and eight patients were T3. Eleven patients received preoperative induction chemotherapy (IC). Sixty patients received transoral laser microsurgery (TLM), and 10 patients received transoral robotic surgery (TORS). Fifty‐eight patients were scored Grade‐1 by water swallow test, and 49 patients were scored Grade 0 by grade, roughness, breathiness, asthenia, strain. The 1, 3, and 5 year OS of all were 95.450%, 84.877%, and 78.026%, and RFS were 89.167%, 78.052%, and 75.451% respectively. Kaplan–Meier survival analysis showed N stage and clinical stage were associated with OS, smoking, clinical stage, surgical margins, and Ki‐67 index were associated with RFS. There were no significant differences in preoperative IC or direct surgery, TLM, or TORS. Cox analyses showed smoking and surgical margins were independent prognosis factors for RFS. Conclusions The positive margin, Ki‐67 index ≥40% and P53(+)&Ki‐67 index ≥40% are worse factors affecting recurrence for SGLC patients. Both smoking and surgical margins are independent prognostic factors affecting recurrence.

Abstract In vitro models coupled with multimodal approaches are needed to dissect the dynamic response of local tumor immune microenvironment (TIME) to immunotherapy. Here the patient‐derived primary lung cancer organoids (pLCOs) are generated by isolating tumor cell clusters, including the infiltrated immune cells. A function‐associated single‐cell RNA sequencing (FascRNA‐seq) platform allowing both phenotypic evaluation and scRNA‐seq at single‐organoid level is developed to dissect the TIME of individual pLCOs. The analysis of 171 individual pLCOs derived from seven patients reveals that pLCOs retain the TIME heterogeneity in the parenchyma of parental tumor tissues, providing models with identical genetic background but various TIME. Linking the scRNA‐seq data of individual pLCOs with their responses to anti‐PD‐1 (αPD‐1) immune checkpoint blockade (ICB) allows to confirm the central role of CD8+ T cells in anti‐tumor immunity, to identify potential tumor‐reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity, including CD99 gene. In summary, the study constructs a joint phenotypic and transcriptomic FascRNA‐seq platform to dissect the dynamic response of local TIME under ICB treatment, providing a promising approach to evaluate novel immunotherapies and to understand the underlying molecular mechanisms.

Abstract The use of trastuzumab emtansine (T‐DM1) has revealed significant efficacy in HER2‐positive metastatic breast cancer (MBC). However, optimal therapeutic strategies following T‐DM1 failure remain a subject of debate in clinical practice. In this multicenter, retrospective, real‐world study, we sought to examine the effectiveness and safety of tyrosine kinase inhibitors (TKIs) as a therapeutic strategy in HER2‐positive MBC who developed T‐DM1 resistance. Between September 2018 and December 2022, 66 patients were enrolled. The median progression‐free survival of TKIs‐based therapy was 10.1 months (95% CI, 4.7–15.6). Objective response rate and clinical benefit rate were 18.2 and 66.7%, respectively. TKIs‐based therapy demonstrated better effectiveness in patients who had previously derived benefit from T‐DM1 and featured acquired resistance to trastuzumab. The most common adverse events were diarrhea (36, 54.5%), hand‐foot syndrome (31, 47.0%), and leucopenia (30, 45.5%). In conclusion, TKIs‐based therapy showed promising effectiveness and safety in HER2‐positive MBC patients after T‐DM1 failure.

Abstract Enhanced Loran (eLoran) is the most important backup system for Global Navigation Satellite System (GNSS). However, most current eLoran demodulation methods are based on digital signal processing, which may produce large errors under the influence of strong interference or noise. The authors propose an eLoran signal message prediction algorithm based on deep learning. Using time‐frequency (TF) analysis convert one‐dimensional signal into two‐dimensional high‐resolution image. It improves Alexnet by adjusting the convolutional layer structure, adding an attention module, and reducing the pooling layer window to construct the Alexnet‐ECA network. The network is used to identify TF image features and predict signal message. The experimental results show that novel method for eLoran signal message prediction based on Alexnet‐ECA can achieve high accuracy and robustness in various SNR scenarios. The accuracy is more than 90% at SNR greater than 10db and not less than 80% even in the complex environments. Compared with Resnet34 and VGG16 networks, Alexnet‐ECA demonstrates its efficiency and effectiveness using real measurement data. This method can enhance the performance and reliability of eLoran receivers and applications.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Abstract The temperature distribution of ultrahigh voltage (UHV) converter transformer is the key to its service life, allowable load and safe operation. The influence of a high‐proportion and large‐value harmonic current on the magnetic field, loss and temperature distribution of a UHV converter transformer is studied. A new calculation method is proposed to determine the winding temperature under the combined actions of multiple key factors. First, the skin effect of UHV converter transformer winding under high proportion and high current harmonics is analysed extensively. It is found that the increase of harmonic current frequency leads to exponential increase of winding loss and temperature by changing skin depth. Second, based on the superposition principle, a calculation method for winding loss considering harmonic current and different load rates is developed. The temperature distribution under different harmonic current frequencies and contents is obtained. The winding losses and temperature under different harmonic currents are quantified. Finally, a new calculation method is proposed for the converter transformer winding temperature, considering the combined actions of factors such as load rate, cooling oil inlet rate and temperature, harmonic current frequency and content. Experimental verification showed an error of only 0.58 K in the actual transformer hotspot temperature, confirming the effectiveness of this method. This method is of great significance for temperature control and safe operation of UHV converter transformers.

Abstract A THz radar, with its wide bandwidth, is capable of high‐resolution imaging down to the centimeter scale. In this study, a THz radar is applied to detect hydrometeors generated in a spray chamber. The observed backscattering signals show fluctuations at centimeter scales, indicating various hydrometeor distribution patterns along the radar beam. A co‐located High‐Speed Imaging (HSI) sensor is used to measure the Drop Size Distributions (DSD) in the spray chamber. The radar sampling beam is well aligned with the HSI probes, allowing an objective comparison between the remote sensing and in situ observations. In this study, the observed radar power is compared with the power estimated from the HSI measurements. Results show great consistency, with power difference smaller than 0.5 dB. This study demonstrates the feasibility and great potential of using a THz radar for ultra‐high‐resolution observations of clouds in a laboratory facility, and in the real atmosphere.

Abstract Neuropathic pain can occur during the prediabetic stage, even in the absence of hyperglycemia. The presence of prediabetic neuropathic pain (PDNP) poses challenges to the management of individuals with prediabetes. However, the mechanisms underlying this pain remain unclear. This study aims to investigate the underlying mechanism and identify potential therapeutic targets of PDNP. A prediabetic animal model induced by a high‐energy diet exhibits both mechanical allodynia and thermal hyperalgesia. Furthermore, hyperexcitability and decreased potassium currents are observed in the dorsal root ganglion (DRG) neurons of these rats. TREK1 and TREK2 channels, which belong to the two‐pore‐domain K+ channel (K2P) family and play an important role in controlling cellular excitability, are downregulated in DRG neurons. Moreover, this alteration is modulated by Sortilin, a molecular partner that modulates the expression of TREK1. The overexpression of Sortilin negatively affects the expression of TREK1 and TREK2, leading to increased neuronal excitability in the DRG and enhanced peripheral pain sensitivity in rats. Moreover, the downregulation of Sortilin or activation of TREK1 and TREK2 channels by genetic or pharmacological approaches can alleviate PDNP. Therefore, targeting the Sortilin‐mediated TREK1/2 pathway may provide a therapeutic approach for ameliorating PDNP.

Abstract Spinal cord injury (SCI) has no effective treatment modalities. It faces a significant global therapeutical challenge, given its features of poor axon regeneration, progressive local inflammation, and inefficient systemic drug delivery due to the blood–spinal cord barrier (BSCB). To address these challenges, a new nano complex that achieves targeted drug delivery to the damaged spinal cord is proposed, which contains a mesoporous silica nanoparticle core loaded with microRNA and a cloaking layer of human umbilical cord mesenchymal stem cell membrane modified with rabies virus glycoprotein (RVG). The nano complex more readily crosses the damaged BSCB with its exosome‐resembling properties, including appropriate size and a low‐immunogenic cell membrane disguise and accumulates in the injury center because of RVG, where it releases abundant microRNAs to elicit axon sprouting and rehabilitate the inflammatory microenvironment. Culturing with nano complexes promotes axonal growth in neurons and M2 polarization in microglia. Furthermore, it showed that SCI mice treated with this nano complex by tail vein injection display significant improvement in axon regrowth, microenvironment regulation, and functional restoration. The efficacy and biocompatibility of the targeted delivery of microRNA by nano complexes demonstrate their immense potential as a noninvasive treatment for SCI.

Abstract This study systematically analyzed the molecular mechanism and function of nuclear factor kappa B subunit 2 (NFKB2) in colorectal cancer (CRC) to investigate the potential of NFKB2 as a therapeutic target for CRC. Various experimental techniques, including RNA sequencing, proteome chip assays, and small molecule analysis, were used to obtain a deeper understanding of the regulation of NFKB2 in CRC. The results revealed that NFKB2 was upregulated in a significant proportion of patients with advanced hepatic metastasis of CRC. NFKB2 played an important role in promoting tumor growth through CD8+ T‐cell exhaustion. Moreover, NFKB2 directly interacted with signal transducer and activator of transcription 2 (STAT2), leading to increased phosphorylation of STAT2 and the upregulation of programmed death ligand 1 (PD‐L1). Applying a small molecule inhibitor of NFKB2 (Rg5) led to a reduction in PD‐L1 expression and improved response to programmed death‐1 blockade‐based immunotherapy. In conclusion, the facilitated NFKB2‐STAT2/PD‐L1 axis may suppress immune surveillance in CRC and targeting NFKB2 may enhance the efficacy of immunotherapeutic strategies. Our results provide novel insights into the molecular mechanisms underlying the contribution of NFKB2 in CRC immune escape.

Abstract Objective To summarize the clinical characteristics and imaging manifestations of patients with nonketotic hyperglycemic hemichorea (NH‐HC) and to explore the possible pathogenesis, diagnosis. and treatment of the disease in order to improve the understanding of this disease and avoid misdiagnosis. Methods Retrospective analysis was performed on the case data of five patients with NH‐HC admitted to our hospital in recent years. The patients were treated in the department of endocrinology, department of neurology, and department of neurosurgery in our hospital, respectively. Meanwhile, relevant literatures were consulted for further learning. Results NH‐HC is usually presented as a triad of nonketotic hyperglycemia, lateral chorea, and typical imaging manifestations of head magnetic resonance imaging or computed tomography, but the clinical manifestations are not the same, and imaging features may also be different, presenting a diversified trend in clinical practice. All five patients were given glucose‐lowering drugs and improved with or without combination of drugs to control symptoms of chorea. Conclusion NH‐HC is a rare complication of diabetes, characterized by hyperglycemia and hemichorea. How to identify the extreme situation and make fast judgment is a top priority. Timely and correct control of blood glucose is the key to the treatment, and when necessary, application of dopamine receptor antagonists in patients with combination therapy can accelerate improvement of the clinical symptoms. The prognosis of NH‐HC is good, the clinician should strengthen comprehensive understanding of this disease to avoid missed diagnosis or misdiagnosis and enable patients to get more timely and effective treatment.

Abstract Motor proteins, encoded by Kinesin superfamily (KIF) genes, are critical for brain development and plasticity. Increasing studies reported KIF’s roles in neurodevelopmental disorders. Here, a 6 years and 3 months‐old Chinese boy with markedly symptomatic epilepsy, intellectual disability, brain atrophy, and psychomotor retardation was investigated. His parents and younger sister were phenotypically normal and had no disease‐related family history. Whole exome sequencing identified a novel heterozygous in‐frame deletion (c.265_267delTCA) in exon 3 of the KIF5C in the proband, resulting in the removal of evolutionarily highly conserved p.Ser90, located in its ATP‐binding domain. Sanger sequencing excluded the proband's parents and family members from harboring this variant. The activity of ATP hydrolysis in vitro was significantly reduced as predicted. Immunofluorescence studies showed wild‐type KIF5C was widely distributed throughout the cytoplasm, while mutant KIF5C was colocalized with microtubules. The live‐cell imaging of the cargo‐trafficking assay revealed that mutant KIF5C lost the peroxisome‐transporting ability. Drosophila models also confirmed p.Ser90del's essential role in nervous system development. This study emphasized the importance of the KIF5C gene in intracellular cargo‐transport as well as germline variants that lead to neurodevelopmental disorders and might enable clinicians for timely and accurate diagnosis and disease management in the future.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Bone nonunion and bone defects frequently occur following high‐energy open injuries or debridement surgeries, presenting complex challenges to treatment and significantly affecting patients' quality of life. At present, there are three primary treatment options available for addressing bone nonunion and bone defects: vascularized bone grafts, the Masquelet technique, and the Ilizarov technique. The Ilizarov technique, also known as distraction osteogenesis, is widely favored by orthopedic surgeons because of several advantages, including minimal soft tissue requirements, low infection risk, and short consolidation time. However, in recent years, the application of the Masquelet technique has resulted in novel treatment methods for managing post‐traumatic bone infections when bone defects are present. Although these new techniques do not constitute a panacea, they continue to be the most commonly employed options for treating complex large bone nonunion and bone defects. This review evaluates the currently available research on the Ilizarov and Masquelet bone transport techniques applied at various anatomical sites. Additionally, it explores treatment durations and associated complications to establish a theoretical foundation that can guide clinical treatment decisions and surgical procedures for the management of bone nonunion and bone defects.

Objective Pulmonary embolism, cardiac embolism, and even cerebral embolism due to paraspinal vein leakage (PVL) are increasingly reported, and their risk factors need to be adequately investigated for prevention. To this end, this study investigated the correlation of the distribution and morphological characteristics of fracture lines with the occurrence of PVL after percutaneous vertebroplasty (PVP), which has not been previously reported. Methods Patients with acute single‐segment thoracolumbar osteoporotic vertebral compression fractures (OVCFs) treated with PVP at our institution from January 2019 to July 2022 were selected for a matched case–control study. The case and control groups included those with and without PVL, respectively, matched at a 1:1 ratio based on general clinical characteristics. Additionally, fracture map and heatmap analysis was performed in both groups. In addition to the general clinical characteristics, the vertebral height ratio, puncture angle, delivery rate, and indexes were assessed via the three‐dimensional CT reconstruction fracture line mapping technique, namely, the distribution of fracture lines, fracture line length, main fracture line shape, location of fracture line involvement, and number of fracture line branches, were compared between the two groups. The Wilcoxon rank‐sum test, t tests, analysis of variance, and conditional logistic regression were used for statistical analysis. Results Among 658 patients with OVCFs, 54 who did and 54 who did not develop PVL were included in this study. Significant differences in the puncture angle, fracture line distribution (MR‐1, ML‐2, MM‐2, MR‐2, ML‐3, MM‐3, LL‐1, LM‐1, LL‐2, LM‐2), fracture line involvement of the posterior wall, total fracture line length, and main fracture line length were found between the two groups (p

Abstract The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

Abstract Background Chromosomal translocations involving core binding factor (CBF) genes account for 15% of adult acute myeloid leukemia (AML) cases in China. Despite being classified as favorable‐risk by European Leukemia Net (ELN), CBF‐AML patients have a 40% relapse rate. This study aims to analyze clinical characteristics and prognosis of CBF‐AML, compare its subtypes (inv(16) and t(8;21)), and validate prognostic factors. Methods Retrospective analysis of 149 AML patients (75 CBF‐AML, 74 non‐CBF) at Peking University First Hospital (March 2012–March 2022). Results CBF‐AML patients have significantly lower disease‐free survival (DFS) (p = 0.005) and higher non‐relapse mortality (NRM) (p = 0.028) compared to non‐CBF AML. inv (16) and t(8;21) show distinct co‐occurring gene mutation patterns, with inv(16) being prone to central nervous system (CNS) leukemia. Multivariate analysis identifies age as a risk factor for overall survival (OS) and disease free survival (DFS), kinase mutation as a risk factor for DFS and Recurrence, while WT1 mutation as a risk factor for OS and non relapse mortality (NRM) risk in t(8;21) AML. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) improves prognosis in low‐risk t(8;21). Conclusion Prognosis of CBF‐AML is poorer than ELN guidelines suggest. inv(16) and (8;21) are separate entities with relatively poor prognoses, requiring rational risk stratification strategies. Allo‐HSCT may benefit low‐risk t(8;21), but further research is needed for conclusive evidence.

Abstract Inspired by biological vision mechanism, event‐based cameras have been developed to capture continuous object motion and detect brightness changes independently and asynchronously, which overcome the limitations of traditional frame‐based cameras. Complementarily, spiking neural networks (SNNs) offer asynchronous computations and exploit the inherent sparseness of spatio‐temporal events. Notably, event‐based pixel‐wise optical flow estimations calculate the positions and relationships of objects in adjacent frames; however, as event camera outputs are sparse and uneven, dense scene information is difficult to generate and the local receptive fields of the neural network also lead to poor moving objects tracking. To address these issues, an improved event‐based self‐attention optical flow estimation network (SA‐FlowNet) that independently uses criss‐cross and temporal self‐attention mechanisms, directly capturing long‐range dependencies and efficiently extracting the temporal and spatial features from the event streams is proposed. In the former mechanism, a cross‐domain attention scheme dynamically fusing the temporal‐spatial features is introduced. The proposed network adopts a spiking‐analogue neural network architecture using an end‐to‐end learning method and gains significant computational energy benefits especially for SNNs. The state‐of‐the‐art results of the error rate for optical flow prediction on the Multi‐Vehicle Stereo Event Camera (MVSEC) dataset compared with the current SNN‐based approaches is demonstrated.

Abstract Background The biomarkers of immune checkpoint inhibitors in the treatment of non‐small cell lung cancer (NSCLC) patients have limited predictive performance. In this study we aimed to investigate the feasibility of molecular tumor burden index (mTBI) in circulating tumor DNA (ctDNA) as a predictor for immunotherapy in patients with NSCLC. Methods From February 2017 to November 2020, pretreatment and on‐treatment (3~6 weeks after first cycle of immunotherapy) dynamic plasma ctDNA samples from NSCLC patients receiving immune monotherapy or combination therapy were analyzed by targeted capture sequencing of 1021 genes. PyClone was used to infer the mTBI. The impact of pretreatment mTBI on survival outcomes was verified in the POPLAR/OAK trials. Results We found that patients without detectable baseline ctDNA had better survival outcomes (median overall survival [OS]: not reached vs. 12.8 months; hazard ratio [HR], 0.15; p = 0.035]). RB1 and SMARCA4 mutations were remarkably associated with worse survival outcomes. Furthermore, lower pretreatment mTBI was associated with superior OS (median: not reached vs. 8.1 months; HR, 0.22; p = 0.024) and PFS (median: 32.9 vs. 5.4 months; HR, 0.35; p = 0.045), but not objective response, which was validated in the POPLAR/OAK cohort, suggesting that baseline mTBI was a prognostic factor for NSCLC immunotherapy. Early dynamic changes of mTBI (ΔmTBI) significantly distinguished responsive patients, and patients with mTBI decrease to more than 68% at the final tumor evaluation had longer OS (median: 38.2 vs. 4.0 months; HR, 0.18; p = 0.017) and PFS (median: not reached vs. 2.3 months; HR, 0.24; p = 0.030). Conclusion ΔmTBI had a good sensitivity to identify potential beneficial patients based on the best effect CT scans, demonstrating that mTBI dynamics were predictive of benefit from immune checkpoint blockade.

Abstract Purpose To investigate the clinicopathological characteristics and prognostic factors of early‐stage breast cancer (EBC) with human epidermal growth factor receptor 2 (HER2)‐low expression. Methods The clinicopathological data and follow‐up information of EBC patients with HER2‐low and HER2‐0 expression treated at the Breast Disease Center of Peking University First Hospital from January 2014 to December 2017 were analyzed. The prognosis between HER2‐low and HER2‐0 expression groups and with different hormone receptor (HR) expression were compared by statistics. Meanwhile, the expression of Ki67, androgen receptor (AR), TOPIIa, P53, PTEN, and CK5/6 were also analyzed with the HER2‐low expression and prognosis. Results Retrospectively analyzed 1253 cases of EBC, including 583 (46.5%) cases of HER2‐low breast cancer (BC) and 366 (29.2%) HER2‐0 BC cases. Among the HER2‐low BC patients, 487 (83.5%) were HR‐positive, while 96 (16.5%) were HR‐negative. Among the HER2‐0 BC patients, 265 (72.4%) were HR‐positive, while 101 (27.6%) were HR‐negative. Median follow‐up time was 53 months. The 5‐year disease‐free survival of HER2‐low BC patients was 90.2% (95% confidence interval [CI]: 87.2–93.1), and the 5‐year overall survival was 95.4% (95% CI: 93.3–97.6). Cox regression analysis showed that T stage, lymphovascular invasion, and/or perineural invasion were prognostic factors of HER2‐low BC patients. However, the 5‐year disease‐free survival and overall survival of patients in the HER2‐low and HER2‐0 groups were not significantly different in all patients, but a tendency of better prognosis in HER2‐low group was seen in HR‐negative tumors. Conclusion HER2‐low EBC patients accounted for 46.5% of the patient population. T stage, lymphovascular invasion, and/or perineural invasion were factors affecting the prognosis of BC patients with low HER2 expression. No significant difference in prognosis was noted between HER2‐low and HER2‐0 EBC patients. But in HR‐negative tumors, a tendency of better prognosis was seen in HER2‐low versus HER2‐0.

Abstract A self‐confined solid‐state dewetting mechanism is reported that can fundamentally reduce the use of sophisticated nanofabrication techniques, enabling efficient wafer‐scale patterning of non‐closely packed (ncp) gold nanoparticle arrays. When combined with a soft lithography process, this approach can address the reproducibility challenges associated with colloidal crystal self‐assembly, allowing for the batch fabrication of ncp gold arrays with consistent ordering and even optical properties. The resulting dewetted ncp gold nanoparticle arrays exhibit strong surface lattice resonance properties when excited in inhomogeneous environments under normal white‐light incidence. With these SLR properties, the sensitive plasmonic sensing of molecular interactions is achieved using a simple transmission setup. This study will advance the development of miniaturized and portable devices.

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer‐related death worldwide. Hepatectomy remains the first‐line treatment for patients with resectable HCC. However, the reported recurrence rate of HCC at 5 years after surgery is between 50% and 70%. Tumor‐related factors, including tumor size, number and differentiation, and underlying liver disease are well‐known risk factors for recurrence after treatment. In addition to tumor‐related factors, ever‐increasing amounts of studies are finding that the tumor microenvironment also plays an important role in the recurrence of HCC, including systemic inflammatory response and immune regulation. Based on this, some inflammatory and immune markers were used in predicting postoperative cancer recurrence. These include neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, cytotoxic T cells, and regulatory T cells, among others. In this review, we summarized the inflammatory and immune markers that affect recurrence after HCC resection in order to provide direction for adjuvant therapy after HCC resection and ultimately achieve the goal of reducing recurrence.

Hypertensive nephropathy (HN) is a prevalent complication of hypertension and stands as the second primary reason for end-stage renal disease. Research in clinical settings has revealed that Yanggan Yishui Granule (YGYSG) has significant therapeutic effects on HN. However, the material basis and action mechanisms of YGYSG against HN remain unclear. Consequently, this study utilized a comprehensive method integrating ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), network pharmacology, and molecular docking to delineate the active ingredients and potential therapeutic mechanisms of YGYSG for treating HN. Firstly, sixty distinct components were recognized in total as potential active ingredients in YGYSG by UPLC-Q-TOF/MS. Subsequently, the mechanisms of YGYSG against HN were revealed for the first time using network pharmacology. 23 ingredients played key roles in the complete network and were the key active ingredients, which could affect the renin-angiotensin system, fluid shear stress and atherosclerosis, HIF-1 signaling pathway, and AGE-RAGE signaling pathway in diabetic complications by regulating 29 key targets such as TNF, IL6, ALB, EGFR, ACE, and MMP2. YGYSG could treat HN through the suppression of inflammatory response and oxidative stress, attenuating the proliferation of renal vascular smooth muscle cells, lessening glomerular capillary systolic pressure, and ameliorating renal dysfunction and vascular damage through the aforementioned targets and pathways. Molecular docking results revealed that most key active ingredients exhibited a high affinity for binding to the key targets. This study pioneers in clarifying the bioactive compounds and molecular mechanisms of YGYSG against HN and offers scientific reference into the clinical application.

Background. The COVID-19 pandemic is by far the most significant public health crisis in the 21st century, arousing many psychological concerns like post-traumatic stress disorder (PTSD). Aims. This study is aimed at revealing gender differences and similarities in PTSD symptoms among Chinese adults during COVID-19 pandemic. Methods. Data used in this study were from an online cross-sectional study conducted in February 2020 via a web-based platform. We analyzed data from 558 Chinese adults (334 men and 224 women) with PCL-5 scores over the PTSD criteria. A network analysis was performed to explore the structure of PTSD symptoms for subgroups of men and women. Results. The results showed intrusive thoughts and emotional cue reactivity, together with negative beliefs and negative trauma-related emotions, presented strong positive connections in both men and women. A negative connection between intrusive thoughts and self-destructive/reckless behavior existed among women but not men. Regarding centrality symptoms, women and men had flashbacks and self-destructive/reckless behavior in common, but with differential orders. The most central symptom of PTSD was self-destructive/reckless behavior for women and difficulty concentrating for men. Conclusion. We urge that self-destructive/reckless behaviors and flashbacks, as potential core symptoms of COVID-19-related PTSD, be given more attention in future pandemic-related psychiatric intervention programs.

Objective Hip arthroscopy has recently appeared as a successful therapy in treating borderline developmental dysplasia of the hip (BDDH). This study aimed to describe the minimal 2‐year follow‐up after hip arthroscopy for patients with BDDH in the Asian population and use the combination of lateral center edge angle (LCEA) and alpha angles to detect the appearance of impingement in the BDDH population. Methods This retrospective investigation was conducted utilizing information from arthroscopically treated BDDH patients in 2018 and 2019. The following patient‐reported outcomes were reported: modified Harris Hip Score, Hip Outcome Score‐Activities of Daily Living, International Hip Outcome Tool 12‐component form, and Visual Analog Scale. We also considered the clinical data regarding radiological measurements, intraoperative findings, interventions, complications, and subsequent surgical revisions, in the analysis of combination angles in detecting the occurrence of impingement. Patients with asymptomatic contralateral hips from traumatic hip injury (pelvic fracture) served as the control group. A 2:1 propensity score matching was based on age, sex, and BMI. A receiver operating characteristic curve (ROC) was used to identify the thresholds of combination angles and their accuracies. Results A total of 77 hips met the inclusion and exclusion requirements. After the follow‐up period, most patients showed a considerable improvement in patient‐reported outcomes compared to their preoperative values (P 80.5° could be a reliable predictive factor of impingement in BDDH populations.

Objective Fluid extravasation is a potentially dangerous complication associated with shoulder arthroscopy. Most relevant studies have involved respiratory system, while the primary purpose was to reveal the effects of the fluid extravasation on cardiovascular system and postoperative function. Methods The clinical data of 92 patients was retrospective analyzed, in which 84 cases with rotator cuff injury, three cases with shoulder instability, three cases with fractures of the greater tuberosity of the humerus, and two cases with frozen shoulder. All the patients were undergoing shoulder arthroscopy. The relationship between the basic information of the patients and cardiac index (CI) or pulse pressure variation (PPV) were evaluated by linear regression analysis. The change of CI or PPV at different states were evaluated by the one‐way analysis of variance. The liquid retention (TR) and postoperative clinical outcomes was analyzed using linear regression. Results The preoperative CI was affected by anesthesia status and body position, while PPV was not affected. Multivariate mixed‐effects model analysis of CI found that there was a statistically significant difference in groups of older than 55 years old and those with obesity (BMI > 24). After the operation, the retention of irrigation fluid significantly influenced the circumference of the deltoid (P

Abstract Aims/Introduction The triglyceride‐glucose (TyG) index is a simple and reliable indicator of insulin resistance, and is associated with the development and poor outcomes of cardiovascular disease. Subclinical left ventricular dysfunction (SLVD) is frequently detected in approximately one‐third of diabetes patients, but it has not been established whether the TyG index correlates with SLVD. We carried out this research to evaluate the relationship between the TyG index and SLVD in type 2 diabetes mellitus patients. Materials and Methods This was a cross‐sectional and observational study of 183 type 2 diabetes mellitus inpatients at Nanjing Drum Tower Hospital, Nanjing, China. The TyG index and homeostasis model assessment 2 estimates for insulin resistance (HOMA2‐IR) were calculated from biochemical measurements, and speckle‐tracking echocardiography was carried out. According to global longitudinal strain (GLS) by echocardiography, participants were categorized into the SLVD (GLS

Objective When considering surgical treatment options, many patients who undergo hip arthroscopy value continuing active lifestyles. To address these concerns, the purpose of this study was to determine the effect of preoperative activity level on postoperative patient‐reported outcomes (PROs) in femoroacetabular impingement syndrome (FAIS) patients following hip arthroscopy. Methods Data was retrospectively reviewed for FAIS patients who received hip arthroscopy between 2016 and 2018. Patients were divided into active group and inactive group based on preoperative HOS‐SSS scores. Preoperative active patients were 1:1 propensity‐score matched to inactive patients based on age, sex, BMI, and follow‐up period. PROs (HOS‐ADL, HOS‐ADL, iHOT‐12, mHHS), VAS scores, radiographic measures, performed procedures, complications, and revision surgery were compared and analyzed for both groups by Student's t test. Results A total of 71 patients in the active group and 71 patients in the inactive group were found using propensity‐score matching. Active patients had superior preoperative HOS‐ADL, HOS‐SSS, iHOT‐12, mHHS (p

Abstract Two‐dimensional transition metal dichalcogenides (2D TMDs) present promising applications in various fields such as electronics, optoelectronics, memory devices, batteries, superconductors, and hydrogen evolution reactions due to their regulable energy band structures and unique properties. For emerging spintronics applications, materials with excellent room‐temperature ferromagnetism are required. Although most transition metal compounds do not possess room‐temperature ferromagnetism on their own, they are widely modified by researchers using the emerging strategies to engineer or modulate their intrinsic properties. This paper reviews recent enhancement approaches to induce magnetism in 2D TMDs, mainly using doping, vacancy defects, composite of heterostructures, phase modulation, and adsorption, and also by electron irradiation induction, O plasma treatment, etc. On this basis, the produced effects of these methods for the introduction of magnetism into 2D TMDs are compressively summarized and constructively discussed. For perspective, research on magnetic doping techniques for 2D TMDs materials should be directed toward more reliable and efficient directions, such as exploring advanced design strategies to combine dilute magnetic semiconductors, antiferromagnetic semiconductors, and superconductors to develop new types of heterojunctions; and advancing experimentation strategies to fabricate the designed materials and enable their functionalities with simultaneously pursuing the upscalable growth methods for high‐quality monolayers to multilayers.

Abstract The unsteady three‐dimensional numerical simulation calculation of the vertical axial flow pump device is performed based on CFD to examine the pressure pulsation and energy distribution features of the water flow within the siphon outlet conduit (SOC) under the hydraulic coupling of the pump and the flow conduit. The pressure pulsation signals (PPS) of monitoring points are decomposed using the Hilbert–Huang approach via empirical mode decomposition (EMD) and Hilbert spectrum analysis. The results show that the PPS of monitoring points of the SOC has no obvious periodicity. The low‐frequency range below 20 Hz serves as the primary frequency, and the energy ratio of the high‐frequency signal above 700 Hz is less than 1%. Under the condition of a small flow rate 0.3Qbep, there is obvious high‐frequency pulsation above 500 Hz at the inlet of the upstream section of the SOC, and there are periodic components distributed around 200 Hz. The energy of the pressure pulsation is primarily focused in the low‐frequency range below 40 Hz at the SOC outlet section. The PPS at the top and bottom monitoring points of the hump section are consistent, and the pressure pulsation energy (PPE) is mainly concentrated in the low frequency below 40 Hz. In both the big flow condition (1.2Qbep) and the optimal flow condition (1.0Qbep), the PPE of the monitoring points at the top of the hump section is distributed in the middle and low‐frequency band below 40 Hz, and the energy of monitoring points at the bottom of the hump section is concentrated in the low‐frequency band below 20 Hz, accounting for more than 70%. When the flow rate increases from 0.3Qbep to 1.2Qbep, the peak value of the pressure pulsation coefficient at the main frequency of each monitoring point at the top of the hump section changes little, and the peak value of the pressure pulsation coefficient at the main frequency of each monitoring point at the bottom increases first and then decreases. From the upstream section to the hump section of the SOC, the average frequency of each intrinsic mode function (IMF) of the PPS under different flow conditions shows an overall increasing trend. From the hump section of the SOC to its outlet, the average frequency of each IMF of the PPS decreases under the conditions of 1.0Qbep and 1.2Qbep, and there is no obvious change under the condition of 0.3Qbep.

Abstract Background Multidrug resistance is the biggest barrier on the way to chemotherapy for lung adenocarcinoma (LUAD). For some LUAD patients with cisplatin (DDP) resistance and poor prognoses, the authors put forward RNA nanoparticles (NPs) carrying miR‐301b‐3p Inhibitor. Methods The NPs were composed of miR‐301b‐3p, A549 aptamer (A549apt), and Cyanine 5 in a bottom‐up manner with a 3‐way‐junction (3WJ) structure. Diameter, assembly process, and morphology of NPs were observed by Dynamic Light Scattering, Native‐Polyacrylamide Gel Electrophoresis, and Atomic Force Microscopy. Cell internalisation, toxicity, proliferation, migration, invasion, and apoptosis were assayed by confocal laser scanning microscope, CCK8, colony formation assay, Transwell, western blot, and flow cytometry. Results 3WJ‐apt‐miR was evenly distributed, with diameter of 19.61 ± 0.49 nm and triangular branching structures. The accurate delivery of this NP in vivo was ensured by A549 aptamer featuring specific targeting, with smaller side effects than traditional chemotherapy. Such nanomaterials were effectively internalized by cancer cells, with normal cell activity intact. Cancer cell proliferation, invasion, and migration were suppressed, and DDP sensitivity was enhanced, causing DNA damage and facilitating apoptosis of DDP‐resistant cells. Conclusion Based on RNA self‐assembling, the authors researched the effect of miRNA on DDP sensitivity in LUAD regarding gene regulation. 3WJ‐apt‐miR paves the way for clinical tumour therapy.

Abstract Background Previous studies have suggested the applicability of three classifications of subsolid nodules (SSNs). However, few studies have unraveled the natural history of the three types of SSNs. Methods A retrospective study from two medical centers between November 2007 and November 2017 was conducted to explore the long‐term follow‐up results of three different types of SSNs, which were divided into pure ground‐glass nodules (pGGNs), heterogeneous ground‐glass nodules (hGGNs), and real part‐solid nodules (rPSNs). Results A total of 306 consecutive patients, including 361 SSNs with long‐term follow‐up, were reviewed. The median growth times of pGGNs, hGGNs, and rPSNs were 7.7, 6.0, and 2.0 years, respectively. For pGGNs, the median period of development into rPSNs was 4.6 years, while that of hGGNs was 1.8 years, and the time from pGGNs to hGGNs was 3.1 years (p 0.5 and mediastinum window (MW)‐CTR >0.2, all cases with growth were identified within 5 years. Meanwhile, in SSNs whose LW‐CTR and MW‐CTR were 0, it took over 5 years to detect nodular growth. Pathologically, 90.6% of initial SSNs with LW‐CTR >0 were invasive carcinomas (invasive adenocarcinoma and micro‐invasive adenocarcinoma). Among patients with rPSNs in the initial state, 100.0% of the final pathological results were invasive carcinoma. Cox regression showed that age (p = 0.038), initial maximal diameter (p

Objective Hip preservation surgery has expanded to include treatment of hip pathology in elderly patients. Most data on efficacy of arthroscopy treatment in patients with femoroacetabular impingement syndrome (FAIS) has been generated from Western populations, while studies in the older Asian FAIS population are lacking. Here, we report efficacy of hip arthroscopy for treatment of Asian patients aged 50 years and above. Methods We retrospectively reviewed data from 775 hips that were treated arthroscopically for FAIS between 2016 and 2019. Patients with a history of hip surgery, contralateral surgery during the follow‐up period, lateral center‐edge angle (LCEA)

Abstract Neural interfaces for stable access to the spinal cord (SC) electrical activity can benefit patients with motor dysfunctions. Invasive high‐density electrodes can directly extract signals from SC neuronal populations that can be used for the facilitation, adjustment, and reconstruction of motor actions. However, developing neural interfaces that can achieve high channel counts and long‐term intraspinal recording remains technically challenging. Here, a biocompatible SC hyperflexible electrode array (SHEA) with an ultrathin structure that minimizes mechanical mismatch between the interface and SC tissue and enables stable single‐unit recording for more than 2 months in mice is demonstrated. These results show that SHEA maintains stable impedance, signal‐to‐noise ratio, single‐unit yield, and spike amplitude after implantation into mouse SC. Gait analysis and histology show that SHEA implantation induces negligible behavioral effects and Inflammation. Additionally, multi‐unit signals recorded from the SC ventral horn can predict the mouse's movement trajectory with a high decoding coefficient of up to 0.95. Moreover, during step cycles, it is found that the neural trajectory of spikes and low‐frequency local field potential (LFP) signal exhibits periodic geometry patterns. Thus, SHEA can offer an efficient and reliable SC neural interface for monitoring and potentially modulating SC neuronal activity associated with motor dysfunctions.

Abstract Background ASXL2 encodes proteins involved in epigenetic regulation and the assembly of transcription factors at specific genomic loci. Germline de novo truncating variants in ASXL2 have been implicated in Shashi‐Pena syndrome, which results in features of developmental delay (DD), glabellar nevus flammeus, hypotonia, and cardiac disorders. However, the variants are rare, and the clinical spectrum may be incomplete. Methods The clinical data such as brain MRI were collect. The whole exome sequencing was performed for genetic etiology analysis. Results Here, we report a patient with DD, hypotonia, early atrial septal defect, and abnormal white matter signal. She presented with Shashi–Pena syndrome with a truncated variant in ASXL2 (NM_018263.6, c.2142_2152del, p.Ser714Argfs*5). She died of a digestive tract infection when she was 1 year and 6 months old. Conclusions Our study further expanded the spectrum of phenotypes and genetic variations of the syndrome, and we believe that it is necessary to screen the ASXL2 gene in patients with DD and cardiac and bone disorders.

Abstract Hematogenous metastasis is the main approach for colorectal cancer liver metastasis (CRCLM). However, as the gatekeepers in the tumor vessels, the role of TPCs in hematogenous metastasis remains largely unknown, which may be attributed to the lack of specific biomarkers for TPC isolation. Here, microdissection combined with a pericyte medium‐based approach is developed to obtain TPCs from CRC patients. Proteomic analysis reveals that TRP channel‐associated factor 2 (TCAF2), a partner protein of the transient receptor potential cation channel subfamily M member 8 (TRPM8), is overexpressed in TPCs from patients with CRCLM. TCAF2 in TPCs is correlated with liver metastasis, short overall survival, and disease‐free survival in CRC patients. Gain‐ and loss‐of‐function experiments validate that TCAF2 in TPCs promotes tumor cell motility, epithelial‐mesenchymal transition (EMT), and CRCLM, which is attenuated in pericyte‐conditional Tcaf2‐knockout mice. Mechanistically, TCAF2 inhibits the expression and activity of TRPM8, leading to Wnt5a secretion in TPCs, which facilitates EMT via the activation of the STAT3 signaling pathway in tumor cells. Menthol, a TRPM8 agonist, significantly suppresses Wnt5a secretion in TPCs and CRCLM. This study reveals the previously unidentified pro‐metastatic effects of TPCs from the perspective of cold‐sensory receptors, providing a promising diagnostic biomarker and therapeutic target for CRCLM.

Abstract Stage III non‐small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this consensus emphasizes that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure is scientific evidence from clinical research. Finally, based on the level of evidence and strength of recommendations, this consensus provides recommendations for the management of stage III NSCLC from six perspectives. The objective of this consensus is to help clinicians choose the best treatment and promote the standardization of stage III NSCLC diagnosis and treatment in China.

Abstract MicroRNAs (miRNAs) are a class of non‐coding single‐stranded RNA molecules with a length of approximately 18‐25 nt nucleotides that regulate gene expression post‐transcriptionally. MiR‐204‐5p originates from the sixth intron of the transient receptor potential cation channel subfamily M member 3 (TRPM3) gene. MiR‐204‐5p is frequently downregulated in various cancer types and is related to the clinicopathological characteristics and prognosis of cancer patients. So far, many studies have determined that miR‐204‐5p functions as a tumor suppressor for its extensive and powerful capacity to inhibit tumor proliferation, metastasis, autophagy, and chemoresistance in multiple cancer types. MiR‐204‐5p appears to be a promising prognostic biomarker and a therapeutic target for human cancers. This review summarized the latest advances on the role of miR‐204‐5p in human cancers.

Abstract There is a high level of conservation of tryptophans within the active site architecture of the cellulase family, whereas the function of the four tryptophans in the catalytic domain of Cel7A is unclear. By mutating four tryptophan residues in the catalytic domain of Cel7A from Penicillium piceum (PpCel7A), the binding affinity between PpCel7A and p‐nitrophenol‐d‐cellobioside (pNPC) was reduced as determined by Michaelis–Menten constants, molecular dynamics simulations, and fluorescence spectroscopy. Furthermore, PpCel7A variants showed a reduced level of cellobiohydrolase (CBH) activity against cellulose analogs or natural cellulose. Therefore, it could be concluded four tryptophan residues in Cel7A played a critical role in substrate binding. Mutagenesis results indicated that the W390 stacking interactions at the −2 site played an essential role in facilitating substrate distortion to the −1 site. As soon as the function was altered, the mutation would inevitably affect the catalytic activity against the natural substrate. Interestingly, no clear relationship was found between the CBH activity of PpCel7A variants against pNPC and Avicel. p‐Nitrophenol contains many electrophilic groups that may result in overestimation of the binding constant between tryptophan residues and pNPC in comparison with the natural substrate. Consequently, screening improved cellulase using cellulose analogs would divert attention from the target direction for lignocellulose biorefinery. Clarifying mechanism of catalytic diversity on the natural cellulose or cellulose analogs may give better insight into cellulase screening and selecting strategy.

Abstract The effect of aerosols on the properties of clouds is a large source of uncertainty in predictions of weather and climate. These aerosol‐cloud interactions depend critically on the ability of aerosol particles to form cloud droplets. A challenge in modeling aerosol‐cloud interactions is the representation of interactions between turbulence and cloud microphysics. Turbulent mixing leads to small‐scale fluctuations in water vapor and temperature that are unresolved in large‐scale atmospheric models. To quantify the impact of turbulent fluctuations on cloud condensation nuclei (CCN) activation, we used a high‐resolution Large Eddy Simulation of a convective cloud chamber to drive particle‐based cloud microphysics simulations. We show small‐scale fluctuations strongly impact CCN activity. Once activated, the relatively long timescales of evaporation compared to fluctuations causes droplets to persist in subsaturated regions, which further increases droplet concentrations.

A widely utilized tool in reactor analysis is passive tracers that report the residence time distribution, allowing estimation of the conversion and other properties of the system. Recently, advances in microrobotics have introduced powered and functional entities with sizes comparable to some traditional tracers. This has motivated the concept of Smart Tracers that could record the local chemical concentrations, temperature, or other conditions as they progress through reactors. Herein, the design constraints and advantages of Smart Tracers by simulating their operation in a laminar flow reactor model conducting chemical reactions of various orders are analyzed. It is noted that far fewer particles are necessary to completely map even the most complex concentration gradients compared with their conventional counterparts. Design criteria explored herein include sampling frequency, memory storage capacity, and ensemble number necessary to achieve the required accuracy to inform a reactor model. Cases of severe particle diffusion and sensor noise appear to bind the functional upper limit of such probes and require consideration for future design. The results of the study provide a starting framework for applying the new technology of microrobotics to the broad and impactful set of problems classified as chemical reactor analysis.