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ABSTRACT Introduction Immunotherapy has revolutionized the management of lung cancer and improved lung cancer survival in trials, but its real‐world impact at the population level remains unclear. Methods Using data obtained from eight Surveillance, Epidemiology, and End Results (SEER) registries from 2004 through 2019, we addressed the long‐term trends in the incidence, incidence‐based mortality (IBM), and survival of lung cancer patients in the United States. Results The incidence and IBM of both non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) all significantly decreased steadily from 2004 to 2019. The 1‐year survival (1‐YS) of both NSCLC and SCLC improved over time, with the best improvement observed for Stage 4 NSCLC. Two significant turning points of Stage 4 NSCLC 1‐YS were observed over the years: 0.63% (95% confidence interval [CI]: 0.33%–0.93%) from 2004 to 2010, 0.81% (95% CI: 0.41%–1.21%) from 2010 to 2014 and a striking 2.09% (95% CI: 1.70%–2.47%) from 2014 to 2019. The same two turning points in 1‐YS were pronounced for Stage 4 NSCLC in women, which were coincident with the introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) and immunotherapy. However, for Stage 4 NSCLC in men, only one significant turning point in the 1‐YS starting in 2014 was found, which might only correspond to immunotherapy. Significant period effects in reduced IBM were also observed for both Stage 4 AD and Stage 4 SQCC during the period. Conclusion This SEER analysis found that immunotherapy improved the survival of Stage 4 NSCLC patients at the population level in the United States. This real‐world evidence confirms that immunotherapy has truly revolutionized the management of lung cancer.

There has been increasing application of autologous costal chondral/osteochondral transplantation (ACCT/ACOT) and costa‐derived chondrocyte implantation (ACCI) for articular cartilage repair over the past three decades. This review presents the major evidence on the properties of costal cartilage and bone and their qualifications as grafts for articular cartilage repair, the major clinical applications, and the risks and strategies for costal chondral/osteochondral graft(s) harvest. First, costal cartilage has many specific properties that help restore the articular surface. Costa, which can provide abundant cartilage and cylindrical corticocancellous bone, preserves permanent chondrocyte and is the largest source of hyaline cartilage. Second, in the past three decades, autologous costal cartilage‐derived grafts, including cartilage, osteochondral graft(s), and chondrocyte, have expanded their indications in trauma and orthopaedic therapy from small to large joints, from the upper to lower limbs, and from non‐weight‐bearing to weight‐bearing joints. Third, the rate of donor‐site complications of ACCT or ACOT is low, acceptable, and controllable, and some skills and accumulated experience can help reduce the risks of ACCT and ACOT. Costal cartilage‐derived autografting is a promising technique and could be an ideal option for articular chondral lesions with or without subchondral cysts. More high‐quality clinical studies are urgently needed to help us further understand the clinical value of such technologies.

Esophageal squamous cell carcinoma (ESCC), the most common pathological type of esophageal cancer, is one of the leading causes of cancer death worldwide, but an effective therapeutic avenue is still absent. This study was to evaluate the therapeutic effect of Agaricus blazei Murrill polysaccharides (ABP) and Enteromorpha prolifera polysaccharides (EP) on ESCC. The results showed that both ABP and EP have therapeutic effects on multiple malignant processes of ESCC, such as proliferation, migration, invasion, and apoptosis, in vitro. Moreover, both ABP and EP retard tumor growth in vivo and the growth of ESCC-derived organoids. A series of genes and proteins changed upon treatments with ABP and EP after RNA sequencing and proteomics analysis. Autophagy, mitophagy and ferroptosis were enriched after treatments with these two polysaccharides, suggesting that the consumption of ABP and EP may represent a promising dietary supplement for ESCC therapy.

Summary: Background: Perceived delays in cancer drug approvals have been a major concern for policymakers in China. Policies have been implemented to accelerate the launch of new cancer drugs and indications. This study aimed to assess similarities and differences between China and the United States in the approvals, timing, and clinical benefit evidence of cancer drug indications between 2001 and 2020. Methods: This study retrospectively identified all cancer drugs and indications approved in both China and the United States from January 1st, 2001 to December 31, 2020, and described differences in approval times as well as in submission and review times. Information on the availability of overall survival benefit evidence by December 31, 2020, was collected. Univariate and multiple logistic regression analyses were used to assess whether evidence of benefit and other factors affected the propensity and timing of approvals of cancer drug indications in China. Findings: Between 2001 and 2020, 229 indications corresponding to 145 cancer drugs approved in the United States were identified. Of those, 80 indications (34.9%) were also approved in China by the end of 2020. Cancer drug indications were approved in China at a median of 1273.5 days after approval in the United States. The median submission and review time differences for cancer drug indications in China were 1198.0 days and 180.0 days respectively. Submission time differences accounted for most of the approval time differences (p

Objective Osteochondral lesions of the talus (OLT) is a common and clinically challenging disease. The optimal management is still under debate. The purpose of this prospective study was to investigate the feasibility and clinical outcomes of autologous costal osteochondral transplantation (ACOT) for the treatment of cystic OLT. Methods From November 2021 to April 2023, five patients underwent autologous costal osteochondral transplantation (ACOT) for cystic OLT. The demographic data was described, including age, gender, lesion size and location. We prospectively evaluated their functional and imaging outcomes of the five patients for 12 months postoperatively, including numeric rating score (NRS) for pain when walking, Tegner score, American Orthopedic Foot & Ankle Society (AOFAS) score and Foot and Ankle Ability Measure (FAAM) score, and imaging results. A paired t‐test was used for preoperative and postoperative comparison of the paired‐design dataset. Results The average age was 36.6 ± 11.1 years. The average diameter of chondral lesions was 14.95 ± 2.71 mm, the average diameter of subchondral cysts was 10.66 ± 1.84 mm, and their average depth was 10.40 ± 1.86 mm. At 12 months postoperatively, the clinical function indexes improved significantly, including NRS (from 5.2 ± 2.3 to 0), Tegner score (from 3.2 ± 0.4 to 5.8 ± 0.4), AOFAS score (from 72.8 ± 10.0 to 98.2 ± 4.0), and FAAM score (FAAM/ADL from 61.2 ± 24.7 to 99.3 ± 1.6; FAAM/Sports from 32.5 ± 13.73 to 96.3 ± 8.4). Their magnetic resonance observation of cartilage repair tissue (MOCART) scores reached 78.0 ± 7.6 points. ICRS scores of three patients were nearly normal (10 or 11 points). The biopsy of the surviving grafts showed plenty of hyaline cartilage matrix and scattered chondrocytes histologically. No major severe complications were reported during the 12 months follow‐up. Conclusion ACOT could significantly relieve the symptoms of patients with OLT and improve their clinical function at short‐term follow‐up. ACOT might be a feasible and useful method for repairing OLT with subchondral cysts.

Abstract Emerging evidence indicates that SOX2 is an oncogene for esophageal squamous cell carcinoma (ESCC). However, direct targeting of SOX2 is not feasible given that this transcription factor plays important roles in the maintenance of tissues such as the brain. Here, we identified CDP (Homeobox protein cut-like 1 or CASP) as a unique SOX2 binding partner enriched in ESCC with Duolink proximity ligation assay, bimolecular fluorescence complementation (BiFc) and immunoprecipitation. We then screened a peptide aptamer library using BiFc and immunoprecipitation and identified several peptide aptamers, including P58, that blocked the CDP/SOX2 interaction, leading to the inhibition of ESCC progress in vitro and in vivo. Upon administration, synthetic peptide P58, containing the YGRKKRRQRRR cell-penetrating peptide and the fluorophore TAMRA, also blocked the growth and metastasis of ESCC in both mice and zebrafish. Therefore, targeting the SOX2 binding partner CDP with peptide P58 offers an alternative avenue to treat ESCC with increased SOX2 levels.

Topology optimization focuses on the conceptual design of structures, characterized by a large optimization space and a significant impact on structural performance, and has been widely applied in industrial fields such as aviation and aerospace. However, most topology optimization methods prioritize structural stiffness and often overlook stress levels, which are critical factors in engineering design. In recent years, explicit topology optimization methods have been extensively developed due to their ability to produce clear boundaries and their compatibility with CAD/CAE systems. Nevertheless, research on incorporating stress constraints within the explicit topology optimization framework remains scarce. This paper is dedicated to investigating stress constraints within the explicit topology optimization framework. Due to the clear boundaries and absence of intermediate density elements in the explicit topology optimization framework, this approach avoids the challenge of stress calculation for intermediate density elements encountered in the traditional density method. This provides a natural advantage in solving topology optimization problems considering stress constraints, resulting in more accurate stress calculations. Compared with existing approaches, this paper proposes a novel component topology description function that enhances the deformability of components, improving the representation of geometric boundaries. The lower-bound Kreisselmeier–Steinhauser aggregation function is employed to manage the stress constraint, reducing the solution scale and computational burden. The effectiveness of the proposed method is demonstrated through two classic examples of topology optimization.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is increasingly observed in non-obese individuals. The ZJU (Zhejiang University) index has been established as a new and efficient tool for detecting NAFLD, but the relationship between the ZJU index and NAFLD within non-obese individuals still remains unclear.MethodsA post-hoc evaluation was undertaken using data from a health assessment database by the Wenzhou Medical Center. The participants were divided into four groups based on the quartile of the ZJU Index. Cox proportional hazards regression, Kaplan-Meier analysis and tests for linear trends were used to evaluate the relationship between the ZJU index and NAFLD incidence. Subgroup analysis was conducted to test the consistency of the correlation between ZJU and NAFLD in subsgroups. Receiver operative characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the ZJU index, compared with the Atherogenic index of plasma (AIP) and Remnant lipoprotein cholesterol (RLP-C) index.ResultsA total of 12,127 were included in this study, and 2,147 participants (17.7%) developed NAFLD in 5 years follow-up. Participants in higher ZJU quartiles tended to be female and have higher liver enzymes (including ALP, GGT, ALT, AST), GLU, TC, TG, LDL and higher NAFLD risk. Hazard Ratios (HR) and 95% confidence intervals (CI) for new-onset NAFLD in Q2, Q3, and Q4 were 3.67(2.43 to 5.55), 9.82(6.67 to 14.45), and 21.67(14.82 to 31.69) respectively in the fully adjusted model 3. With increased ZJU index, the cumulative new-onset NAFLD gradually increased. Significant linear associations were observed between the ZJU index and new-onset NAFLD (p for trend all

Abstract Solar arrays are the primary energy source for spacecraft. Although traditional rigid solar arrays improve power supply, the quality increases proportionally. Hence, it is difficult to satisfy the requirements of high-power and low-cost space applications. In this study, a shape-memory polymer composite (SMPC) boom was designed, fabricated, and characterized for flexible reel-type solar arrays. The SMPC boom was fabricated from a smart material, a shape-memory polymer composite, whose mechanical properties were tested. Additionally, a mathematical model of the bending stiffness of the SMPC boom was developed, and the bending and buckling behaviors of the boom were further analyzed using the ABAQUS software. An SMPC boom was fabricated to demonstrate its shape memory characteristics, and the driving force of the booms with varying geometric parameters was investigated. We also designed and manufactured a reel-type solar array based on an SMPC boom and verified its self-deployment capability. The results indicated that the SMPC boom can be used as a deployable unit to roll out flexible solar arrays.

Cardiovascular diseases (CVDs) are highly prevalent, sudden onset, and relatively fatal, posing a significant public health burden. Long-term dynamic electrocardiography, which can continuously record the long-term dynamic ECG activities of individuals in their daily lives, has high research value. However, ECG signals are weak and highly susceptible to external interference, which may lead to false alarms and misdiagnosis, affecting the diagnostic efficiency and the utilization rate of healthcare resources, so research on the quality of dynamic ECG signals is extremely necessary. Aimed at the above problems, this paper proposes a dynamic ECG signal quality assessment method based on CNN and LSTM that divides the signal into three quality categories: the signal of the Q1 category has a lower noise level, which can be used for reliable diagnosis of arrhythmia, etc.; the signal of the Q2 category has a higher noise level, but it still contains information that can be used for heart rate calculation, HRV analysis, etc.; and the signal of the Q3 category has a higher noise level that can interfere with the diagnosis of cardiovascular disease and should be discarded or labeled. In this paper, we use the widely recognized MIT-BIH database, based on which the model is applied to realistically collect exercise experimental data to assess the performance of the model in dealing with real-world situations. The model achieves an accuracy of 98.65% on the test set, a macro-averaged F1 score of 98.5%, and a high F1 score of 99.71% for the prediction of Q3 category signals, which shows that the model has good accuracy and generalization performance.

In light of recent advancements in synchrotron radiation technology and nano-technology, there has been a marked increase in the need for ultra-precision nano-positioning mechanisms. This paper presents a method that integrates physical models with multi-objective optimization for developing an optical angle nano-positioning mechanism. We begin by examining the actual motion law of the mechanism, based on kinematic principles. The outcomes from this kinematic analysis facilitate a static analysis of the flexible hinge, identified as a critical component of the mechanism. Subsequently, we establish a dynamic model for the entire mechanism. By employing the physical model as a base and combining it with the optimization algorithm, we identify the optimal design parameters for the mechanism. The design achieves a resolution of 50 nrad and meets the specified requirements. The first-order inherent frequency of the mechanism is approximately 43.75 Hz. There is a discrepancy of 2.63% from the finite element modal analysis results and a 3.33% difference from the theoretical analysis results, validating the reliability of the design method proposed in this study.

Steady-state visual evoked potential (SSVEP) based brain-computer interfaces (BCIs) have achieved an information transfer rate (ITR) of over 300 bits/min, but abundant training data is required. The performance of SSVEP algorithms deteriorates greatly under limited data, and the existing time-shift data augmentation method fails to improve it because the phase-locked requirement between training samples is violated. To address this issue, this study proposes a novel augmentation method, namely phase-locked time-shift (PLTS), for SSVEP-BCI. The similarity between epochs at different time moments was evaluated, and a unique time-shift step was calculated for each class to augment additional data epochs in each trial. The results showed that the PLTS significantly improved the classification performance of SSVEP algorithms on the BETA SSVEP datasets. Moreover, under the condition of one calibration block, by slightly prolonging the calibration duration (from 48 s to 51.5 s), the ITR increased from ${40.88}\pm {4.54}$ bits/min to ${122.61}\pm {7.05}$ bits/min with the PLTS. This study provides a new perspective on augmenting data epochs for training-based SSVEP-BCI, promotes the classification accuracy and ITR under limited training data, and thus facilitates the real-life applications of SSVEP-based brain spellers.

Objective The effectiveness of autologous osteoperiosteal transplantation (AOPT) for the treatment of large cystic talar osteochondral lesions (OCLs) should be further evaluated, and the postoperative cartilage coverage is questionable. The purpose of this retrospective observational study was to investigate the clinical outcomes of AOPT for the treatment of large cystic talar OCLs and to report second‐look arthroscopic results. Methods From June 1, 2017, to June 1, 2021, all talar OCLs at our center were reviewed. Painful cystic lesions treated with AOPT were included in the study. The American Orthopaedic Foot and Ankle Society (AOFAS; 0–100 points) ankle‐hindfoot score, Foot Function Index (FFI; 0–100 points), visual analog scale (VAS; 0–10 points) score, and Tegner score (0–10 points) were used to describe pain and functional outcomes. Furthermore, complications, patient‐reported satisfaction degrees, imaging results (including computed tomography and magnetic resonance), and second‐look arthroscopic evaluation data were also collected for analysis. Results A total of 29 cases were eligible for the study, and 26 responded to the latest follow‐up request, with a mean follow‐up duration of 30.2 (range, 12–57) months. The AOFAS score improved from 69.2 ± 10.9 preoperatively to 80.9 ± 10.0 at the latest follow‐up (p = 0.000). The FFI score improved from 30.4 ± 18.4 preoperatively to 16.3 ± 14.0 at the latest follow‐up (p = 0.000). The VAS pain score improved from 4.0 ± 2.1 preoperatively to 2.5 ± 2.0 at the latest follow‐up (p = 0.001). No donor site morbidity was found. The mean postoperative MOCART score was 57.7 ± 9.5. Second‐look arthroscopy showed a fibrillated cartilage‐like surface at the lesion site in most cases, while two cases exhibited a nearly normal surface. Conclusion The transplantation of osteoperiosteal cylinder autografts taken from the iliac crest for the treatment of large cystic talar OCLs yielded acceptable clinical results. Good integration of the bony part was observed, but cartilage regeneration remained uncertain.

Elevated SOX2 protein levels correspond to the poor prognosis of patients with esophageal squamous cell carcinoma (ESCC). Poor prognosis is closely correlated with the loss or disruption of cellular polarity; however, the relationships between SOX2 protein and polarity proteins in ESCC remain elusive. Herein, we found that the knockdown of SOX2 significantly decreased miR-142-3p expression and can regulate the translation of LLGL2 protein, a member of the Scribble complex. LLGL2 protein levels in ESCC are negatively correlated with miR-142-3p and SOX2 levels. Moreover, LLGL2 protein expression increased upon SOX2 knockdown in ESCC cell lines, and mutating the binding site for this miRNA in the LLGL2 3’-UTR disrupted its ability to inhibit LLGL2 expression. When LLGL2 was overexpressed, ESCC cell proliferation and invasion were inhibited in vitro and in vivo, which could be elucidated based on changes in gene expression after RNA sequencing, targeted proteomic analysis and bioinformatic assays. However, SOX2 protein did not directly bind to the promoter of miR-142-3p after ChIP sequencing. Together, these findings indicate that a SOX2 regulatory axis governs ESCC proliferation, migration, invasiveness, and apoptosis, thereby providing a potential avenue for future therapeutic intervention. Abbreviations CCK-8, Cell Counting Kit 8; Chip, Chromatin Immunoprecipitation; EC, Esophageal cancer; EMT, epithelial-to-mesenchymal transition; ESCC, Esophageal squamous cell carcinomas; LLGL2, lethal (2) giant larvae protein homolog 2; LLGL2ov, LLGL2 overexpression; MET, mesenchymal-epithelial transition; miRNAs, MicroRNAs; PRM-MS, Parallel reaction monitoring-Mass spectrometry; SD, Standard deviation; SOX, sex determining region Y (SRY)-like box; SOX2-Kd, SOX2-knockdwon; TUNEL, TdT-mediated dUTP Nick-End Labeling.

SOX2 is a transcription factor belonging to the SOX gene family, whose activity has been associated with the maintenance of the stemness and self-renewal of embryonic stem cells (ESCs), as well as the induction of differentiated cells into induced pluripotent stem cells (iPSCs). Moreover, accumulating studies have shown that SOX2 is amplified in various cancers, notably in esophageal squamous cell carcinoma (ESCC). In addition, SOX2 expression is linked to multiple malignant processes, including proliferation, migration, invasion, and drug resistance. Taken together, targeting SOX2 might shed light on novel approaches for cancer therapy. In this review, we aim to summarize the current knowledge regarding SOX2 in the development of esophagus and ESCC. We also highlight several therapeutic strategies for targeting SOX2 in different cancer types, which can provide new tools to treat cancers possessing abnormal levels of SOX2 protein.

Graphene quantum dots (GQDs) possess the photosensitive absorption for photoelectrochemical hydrogen evolution owing to special band structures, whereas they usually confront with photo-corrosion or undesired charge recombination during photoelectrochemical reactions. Hence, we establish the heterojunction between GQDs and MoSe2 sheets via a hydrothermal process for improved stability and performance. Photoanodic water splitting with hydrogen evolution boosted by the heteroatom doped N,S-GQDs/MoSe2 heterojunction has been attained due to the abundant active sites, promoted charge separation and transfer kinetics with reduced energy barriers. Diphasic 1T and 2H MoSe2 sheet-hybridized quantum dots contribute to the Schottky heterojunction, which can play a key role in expedited carrier transport to inhibit accumulative photo-corrosion and increase photocurrent. Heteroatom dopants lead to favored energy band matching, bandgap narrowing, stronger light absorption and high photocurrent density. The external quantum efficiency of the doped heterojunction has been elevated twofold over that of the non-doped pristine heterojunction. Modification of the graphene quantum dots and MoSe2 heterojunction demonstrate a viable and adaptable platform toward photoelectrochemical hydrogen evolution processes.

Background: The purpose of this study was to evaluate the impact of glucose levels on admission, on the risk of 30-day major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI), and to assess the difference in outcome between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients. Methods: This study was a post hoc analysis of the Acute Coronary Syndrome Quality Improvement in Kerala Study, and 13,398 participants were included in the final analysis. Logistic regression models were used to assess the association between glucose levels on admission and the risk of 30-day MACEs, adjusting for potential confounders. Results: Participants were divided according to the glucose quintiles. There was a positive linear association between glucose levels at admission and the risk of 30-day MACEs in AMI patients [adjusted OR (95% CI): 1.05 (1.03, 1.07), p < 0.001]. Compared to participants with an admission glucose between 5.4 and 6.3 mmol/L, participants with the highest quintile of glucose level (≥10.7 mmol/L) were associated with increased risk of 30-day MACEs in the fully adjusted logistic regression model [adjusted OR (95% CI): 1.82 (1.33, 2.50), p < 0.001]. This trend was more significant in patients with STEMI (p for interaction = 0.036). Conclusions: In patients with AMI, elevated glucose on admission was associated with an increased risk of 30-day MACEs, but only in patients with STEMI.

Abstract In the evolutionary “arms race” from prokaryotes to eukaryotes, some memories of foreign DNA have been conserved for defensive purposes. Shortly after invasion by the plasmid, pEGFP-N1, the conserved the defense gene, isg15, was activated in the zebrafish zygote and in mammalian cells. Based on the sequence similarity, we found three virus-derived sequences in pEGFP-N1 which share the 5ʹ-GTTTGTT-3ʹ core sequence, an epigenetic factor leading to increased expression of isg15. Mutation of the core sequence greatly reduces the degradation rate of the plasmid in E. coli cells or zebrafish embryos. We conclude that a conserved defense response, common to both eukaryotic and prokaryotic cells, allows identification and degradation of plasmids containing 5ʹ-GTTTGTT-3ʹ.

Brain-computer interface (BCI) usually suffers from the problem of low recognition accuracy and large calibration time, especially when identifying motor imagery tasks for subjects with indistinct features and classifying fine grained motion control tasks by electroencephalogram (EEG)-electromyogram (EMG) fusion analysis. To fill the research gap, this paper presents an end-to-end semi-supervised learning framework for EEG classification and EEG–EMG fusion analysis. Benefiting from the proposed metric learning based label estimation strategy, sampling criterion and progressive learning scheme, the proposed framework efficiently extracts distinctive feature embedding from the unlabeled EEG samples and achieves a 5.40% improvement on BCI Competition IV Dataset IIa with 80% unlabeled samples and an average 3.35% improvement on two public BCI datasets. By employing synchronous EMG features as pseudo labels for the unlabeled EEG samples, the proposed framework further extracts deep level features of the synergistic complementarity between the EEG signals and EMG features based on the deep encoders, which improves the performance of hybrid BCI (with a 5.53% improvement for the Upper Limb Motion Dataset and an average 4.34% improvement on two hybrid datasets). Moreover, the ablation experiments show that the proposed framework can substantially improve the performance of the deep encoders (with an average 5.53% improvement). The proposed framework not only largely improves the performance of deep networks in the BCI system, but also significantly reduces the calibration time for EEG-EMG fusion analysis, which shows great potential for building an efficient and high-performance hybrid BCI for the motor rehabilitation process.

The surface/interface species in perovskite oxides play essential roles in many novel emergent physical phenomena and chemical processes. With low eigen-energies in the terahertz region, such species at buried interfaces remain poorly understood due to the lack of feasible surface-specific spectroscopic probes to resolve the resonances. Here, we show that polarized phonons and two-dimensional electron gas at the interface can be characterized using surface-specific nonlinear optical spectroscopy in the terahertz range. This technique uses intra-pulse difference frequency mixing process, which is allowed only at the surface/interface of a centrosymmetric medium. Submonolayer sensitivity can be achieved using the state-of-the-art detection scheme for the terahertz emission from the surface/interface. Through symmetry analysis and proper polarization selection, background-free Drude-like nonlinear response from the two-dimensional electron gas emerging at the LaAlO3/SrTiO3 or Al2O3/SrTiO3 interface was successfully observed. The surface/interface potential, which is a key parameter for SrTiO3-based interface superconductivity and photocatalysis, can now be determined optically in a nonvacuum environment via quantitative analysis on the phonon spectrum that was polarized by the surface field in the interfacial region. The interfacial species with resonant frequencies in the THz region revealed by our method provide more insights into the understanding of physical properties of complex oxides.

Elevated SOX2 protein levels are closely correlated with the increased incidence of esophageal squamous cell carcinoma (ESCC). However, establishing effective target measures for ESCC treatments continue to be researched. It has been previously proposed that SOX2 represents a potential therapeutic target for ESCC. Here, we found that the enzyme Poly(ADP-Ribose) polymerase 1 (PARP1) enriched in ESCCs interact with SOX2. Inhibition of PARP1 with 3-aminobenzamide (3-ABA) or shRNA knockdown reduced the proliferation of ESCCs, accompanied by decreased protein levels of SOX2. RNA sequencing demonstrated that PARP1 inhibition affected multiple signaling pathways involved in cancer cell proliferation. Additionally, 3-ABA synergistically suppressed the growth of ESCC cells when combined with cisplatin, and metformin potentiated the suppressive effect of 3-ABA on ESCC cell growth. Together these findings suggest that targeting SOX2 binding partner PARP1 provides a possible avenue to treat patients with high levels of SOX2.

Neurotrophic tropomyosin receptor kinase (NTRK) gene fusion has been identified as an oncogenic driver of various solid tumors, and it is rare in non-smalll cell lung cancer (NSCLC) with a frequency of approximately less than 1%. Next-generation sequencing (NGS) is of priority for detecting NTRK fusions, especially RNA-based NGS. Currently, the tropomyosin receptor kinase (TRK) inhibitors have shown promising efficacy and well tolerance in patients with NTRK fusion-positive solid tumors, regardless of tumor histology. The first-generation TRK inhibitors (larotrectinib and entrectinib) are recommended as the first-line treatment for locally advanced or metastatic NSCLC patients with positive NTRK fusion. However, TRK inhibitor resistance can eventually occur due to on-target or off-target mechanisms. Further studies are under investigation to overcome resistance and improve survival. Interestingly, NTRK fusion might be the mechanism of resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) in NSCLC patients with EGFR mutation. Regarding immunotherapy, the efficacy of immune checkpoint inhibitors in NSCLC patients harboring NTRK fusion has yet to be well described. In this review, we elucidate the function of NTRK genes, summarize the diagnostic techniques for NTRK fusions, and present clinical data for TRK inhibitors; we also discuss potential mechanisms of resistance to TRK inhibitors.

Abstract Long noncoding RNAs (lncRNAs) possessed essential functions in the biological behaviors of various human cancers. SLCO4A1 antisense RNA 1 (SLCO4A1‐AS1) is a lncRNA that has been reported as a oncogenic regulator in colorectal cancer and bladder cancer. However, whether it exerted functions in the gene expression and cellular processes in lung adenocarcinoma (LUAD) remains still obscure. In the present research, we unveiled the high level of SLCO4A1‐AS1 in LUAD tissues and cells. Moreover, functional assays indicated that SLCO4A‐AS1 facilitated LUAD cell proliferation, motility, and cisplatin‐resistance. Besides, mechanism investigation revealed that miR‐4701‐5p could interact with SLCO4A1‐AS1 and directly target to NFE2L1. The expression correlation between miR‐4701‐5p and SLCO4A1‐AS1 or NFE2L1 was found to be negative. Moreover, NFE2L1 was expressed at a same tendency with SLCO4A1‐AS1 in LUAD tissues and cells. In addition, it was confirmed that NFE2L1 was involved in SLCO4A1‐AS1‐mediated activation of WNT pathway. According to rescue assays, NFE2L1 could involve in SLCO4A1‐AS1‐mediated LUAD cell growth. Conclusively, our study demonstrated that SLCO4A1‐AS1 facilitated cell growth and enhanced the resistance of LUAD cells to chemotherapy via activating WNT pathway through miR‐4701‐5p/NFE2L1 axis.

ABSTRACTRapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged in the past 2 decades. However, there is no approved antiviral agent against these coronaviruses. We inspected the role of Hsp90 for coronavirus propagation. First, an Hsp90 inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation in cell lines and physiological-relevant human intestinal organoids. Second, siRNA depletion of Hsp90β, but not Hsp90α, significantly restricted MERS-CoV replication and abolished virus spread. Third, Hsp90β interaction with MERS-CoV nucleoprotein (NP) was revealed in a co-immunoprecipitation assay. Hsp90β is required to maintain NP stability. Fourth, 17-AAG substantially inhibited the propagation of SARS-CoV and SARS-CoV-2. Collectively, Hsp90 is a host dependency factor for human coronavirus MERS-CoV, SARS-CoV and SARS-COV-2. Hsp90 inhibitors can be repurposed as a potent and broad-spectrum antiviral against human coronaviruses.

Abstract Background The iliac crest is the most common autogenous bone graft donor site, although associated with postoperative pain, functional disability, cosmesis, morphology and surgical satisfaction. We assessed each aspect above by comparing iliac crest reconstruction with bone cement and screws following harvest with no reconstruction. Methods We evaluated patients who underwent large iliac crest harvesting, including ten patients who underwent iliac crest defect reconstruction with bone cement and cancellous screws (R group) and ten randomly matched patients without reconstruction (NR group) were evaluated prospectively in the same period. Local pain, cosmesis and other complications were assessed postoperatively at 1 week, 6 weeks, 3 months and 6 months. Results Pain, cosmesis and satisfaction of patients significantly differed between the two groups. The R group exhibited less complications and lower pain visual analogue scores at postoperative 1 week (p

Cancer, as the second leading cause of death worldwide, is a major public health concern that imposes a heavy social and economic burden. Effective approaches for either diagnosis or therapy of most cancers are still lacking. Dynamic monitoring and personalized therapy are the main directions for cancer research. Cancer-derived extracellular vesicles (EVs) are potential disease biomarkers. Cancer EVs, including small EVs (sEVs), contain unique biomolecules (protein, nucleic acid, and lipids) at various stages of carcinogenesis. In this review, we discuss the biogenesis of sEVs, and their functions in cancer, revealing the potential applications of sEVs as cancer biomarkers.

Reconstructing extensive cranial defects represents a persistent clinical challenge. Here, we reported a hybrid three-dimensional (3D) printed scaffold with modification of QK peptide and KP peptide for effectively promoting endogenous cranial bone regeneration. The hybrid 3D printed scaffold consists of vertically aligned cryogel fibers that guide and promote cell penetration into the defect area in the early stages of bone repair. Then, the conjugated QK peptide and KP peptide further regulate the function of the recruited cells to promote vascularization and osteogenic differentiation in the defect area. The regenerated bone volume and surface coverage of the dual peptide-modified hybrid scaffold were significantly higher than the positive control group. In addition, the dual peptide-modified hybrid scaffold demonstrated sustained enhancement of bone regeneration and avoidance of bone resorption compared to the collagen sponge group. We expect that the design of dual peptide-modified hybrid scaffold will provide a promising strategy for bone regeneration. [ABSTRACT FROM AUTHOR]

Hematopoiesis is a highly coordinated process that generates all the body's blood cells, and perturbations in embryonic hematopoiesis may result in illnesses ranging from fetal anemia to various leukemias. Correct establishment of hematopoietic progenitor cell fate is essential for the development of adequate blood cell subpopulations, although regulators of cell fate commitment have not been fully defined. Here, we show that primary erythropoiesis and myelopoiesis in zebrafish embryos are synergistically regulated by blf and the drl cluster, as simultaneous depletion led to severe erythrocyte aplasia and excessive macrophage formation at the expense of neutrophil development. Integrative analysis of transcriptome- and genome-wide binding data revealed that blf and drl cluster genes are responsible for constraining the expression of vasculogenesis-promoting genes in the intermediate cell mass and monocytopoiesis-promoting genes in the rostral blood island. This indicates that blf and drl cluster genes act as determinants of the fate commitment of erythroid and myeloid progenitor cells. Furthermore, a rescue screen demonstrated that Zfp932 is a potential mammalian functional equivalent to zebrafish blf and drl cluster genes. Our data provide insight into conserved cell fate commitment mechanisms of primitive hematopoiesis. [ABSTRACT FROM AUTHOR]