Search

Sargassum horneri is one of the important species in the seaweed field in China, which plays an important role in supporting the marine environment and fishery resources. In order to find out whether the Sargassum horneri is a perennial problem and the tolerance temperature of Sargassum horneri, based on the field intertidal monitoring and observation, the ecological process of Sargassum horneri’s decline period in natural habitat was explored by recording the biological parameters such as plant height, trunk diameter, fixator attachment area and water temperature data. The results showed that: (1) at the end of May, Sargassum horneri in the intertidal zone of Gouqi Island began to enter the decline period after breeding and the decline of Sargassum horneri showed obvious seasonal variation (P

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

For low power generation efficiency and water source thermal pollution caused by irrational operation of once-through cooling water systems (OCWSs) in condensing power plants, this paper advances a method to maximize the power plant net power by OCWS operation optimization and a 2 × 330 MW power plant is taken as a study case. First, the power plant thermodynamic system is simulated by Ebsilon to obtain exhausted steam parameters. Then, a heat transfer analysis method for the whole OCWS is investigated to calculate the system water temperature. Next, a maximum net power optimization model is deduced and established. Particularly, the model sets the temperature difference between OCWS outlet and inlet as a constraint. Finally, an improved firefly algorithm is employed to solve the model to get the numbers of constant-speed pumps and variable-speed pumps in operation and the frequency conversion ratio of the latter. This paper analyses the optimization under various scenarios and the sensitivity of optimization results. After optimization, the net power of the case power plant is increased up to 2080.5 kW, approximately 0.524 %. The OCWS temperature difference is decreased under most conditions. The method effectively enhances power plant net power and reduces drainage impact on the environment.

IntroductionThe introduction of Immune Checkpoint Inhibitors (ICIs) has marked a paradigm shift in treating Lung Squamous Cell Carcinoma (LUSC), emphasizing the urgent need for precise molecular biomarkers to reliably forecast therapeutic efficacy. This study aims to identify potential biomarkers for immunochemotherapy efficacy by focusing on plasma extracellular vesicle (EV)-derived long RNAs (exLRs).MethodsWe enrolled 78 advanced LUSC patients undergoing first-line immunochemotherapy. Plasma samples were collected, and exLR sequencing was conducted to establish baseline profiles. A retrospective analysis was performed on 42 patients to identify differentially expressed exLRs. Further validation of the top differentially expressed exLRs was conducted using quantitative reverse transcription PCR (qRT-PCR). Univariate Cox analysis was applied to determine the prognostic significance of these exLRs. Based on these findings, we developed a predictive signature (p-Signature).ResultsIn the retrospective analysis of 42 patients, we identified 460 differentially expressed exLRs, with pathways related to leukocyte migration notably enriched among non-responders. Univariate Cox analysis revealed 45 exLRs with prognostic significance. The top 6 protein-coding exLRs were validated using qRT-PCR, identifying CXCL8, SSH3, and SDHAF1 as differentially expressed between responders and non-responders. The p-Signature, comprising these three exLRs, demonstrated high accuracy in distinguishing responders from non-responders, with an Area Under the Curve (AUC) of 0.904 in the retrospective cohort and 0.812 in the prospective cohort.DiscussionThis study highlighted the potential of plasma exLR profiles in predicting LUSC treatment efficacy. Intriguingly, lower p-Signature scores were associated with increased abundance of activated CD4+ and CD8+ T cells, indicating a more robust immune environment. These findings suggest that the p-Signature could serve as a valuable tool in guiding personalized and effective therapeutic strategies for LUSC.

Proteins, as the primary executors of physiological activity, serve as a key factor in disease diagnosis and treatment. Research into their structures, functions, and interactions is essential to better understand disease mechanisms and potential therapies. DeepMind’s AlphaFold2, a deep-learning protein structure prediction model, has proven to be remarkably accurate, and it is widely employed in various aspects of diagnostic research, such as the study of disease biomarkers, microorganism pathogenicity, antigen-antibody structures, and missense mutations. Thus, AlphaFold2 serves as an exceptional tool to bridge fundamental protein research with breakthroughs in disease diagnosis, developments in diagnostic strategies, and the design of novel therapeutic approaches and enhancements in precision medicine. This review outlines the architecture, highlights, and limitations of AlphaFold2, placing particular emphasis on its applications within diagnostic research grounded in disciplines such as immunology, biochemistry, molecular biology, and microbiology.

Abstract Metabolism of polyamines is of critical importance to physiological processes. Ornithine decarboxylase (ODC) antizyme inhibitors (AZINs) are capable of interacting with antizymes (AZs), thereby releasing ODC from ODC-AZs complex, and promote polyamine biosynthesis. AZINs regulate reproduction, embryonic development, fibrogenesis and tumorigenesis through polyamine and other signaling pathways. Dysregulation of AZINs has involved in multiple human diseases, especially malignant tumors. Adenosine-to-inosine (A-to-I) RNA editing is the most common type of post-transcriptional nucleotide modification in humans. Additionally, the high frequencies of RNA-edited AZIN1 in human cancers correlates with increase of cancer cell proliferation, enhancement of cancer cell stemness, and promotion of tumor angiogenesis. In this review, we summarize the current knowledge on the various contribution of AZINs related with potential cancer promotion, cancer stemness, microenvironment and RNA modification, especially underlying molecular mechanisms, and furthermore explored its promising implication for cancer diagnosis and treatment.

Abstract Recently, advanced adenoma (AA) has been recognized as a target for colorectal cancer (CRC) screening. However, the fecal occult blood test (FOBT), the primary non-invasive screening method, shows limited sensitivity in detecting AA. This study investigates the relationship between adenoma characteristics and FOBT false-negative results. In a retrospective cohort study conducted from 2015 to 2022, we examined 342 inpatients with AA who underwent colonoscopy and received qualitative FOBT. FOBT sensitivity was analyzed about various adenoma characteristics, and logistic regression models were employed to investigate the relationship between adenoma features and FOBT false-negative outcomes. FOBT sensitivity in AA inpatients was 52.63%. Significant differences in sensitivity were observed based on adenoma location (left vs. right), morphology (with or without pedunculation), and size (≤ 10 mm vs. > 10 mm). After adjusting for several potential confounders, FOBT showed a reduced false-negative rate in AA with large-sized (OR, 0.49; 95% CI 0.31–0.77), left-sided location (OR, 0.53; 95% CI 0.31–0.89), and pedunculated morphology (OR, 0.73; 95% CI 0.43–1.24). AA with large size, left-sided location, and pedunculated morphology independently contribute to a decreased rate of FOBT false-negative results. However, these adenoma characteristics are not actively modifiable. Therefore, novel non-invasive methods are needed to improve AA detection accuracy.

Abstract The surge in anthropogenic CO2 emissions from fossil fuel dependence demands innovative solutions, such as artificial photosynthesis, to convert CO2 into value-added products. Unraveling the CO2 photoreduction mechanism at the molecular level is vital for developing high-performance photocatalysts. Here we show kinetic isotope effect evidence for the contested protonation pathway for CO2 photoreduction on TiO2 nanoparticles, which challenges the long-held assumption of electron-initiated activation. Employing isotopically labeled H2O/D2O and in-situ diffuse reflectance infrared Fourier transform spectroscopy, we observe H+/D+-protonated intermediates on TiO2 nanoparticles and capture their inverse decay kinetic isotope effect. Our findings significantly broaden our understanding of the CO2 uptake mechanism in semiconductor photocatalysts.

ObjectiveThe escalating prevalence of chronic pain poses a substantial socio-economic burden. Chronic pain primarily stems from musculoskeletal and nervous system impairments. Given cadmium's known toxicity to these systems, our study sought to investigate the correlation between blood cadmium levels and chronic pain.MethodsThe cross-sectional study was conducted from the National Health and Nutrition Examination Survey (NHANES, 1999–2004), and comprised US adults who participated in a chronic pain interview. We employed logistic regression models and smooth curve fitting to elucidate the relationship between blood cadmium levels and chronic pain.ResultsOur findings revealed a linear association between blood cadmium levels and chronic pain. Compared to the lower blood cadmium tertile 1 (

ObjectiveHigh-density lipoprotein cholesterol (HDL-C) has been reported to be associated with pain symptoms of various diseases, and its anti-inflammatory and antioxidant mediation is related to the pathogenesis of chronic pain. This study aims to evaluate the relationship between HDL-C levels and chronic pain in American adults.MethodsThis cross-sectional study used data from American adults aged 20 and above during the 2003–2004 National Health and Nutrition Examination Survey (NHANES) cycle. Participants were divided into 4 groups based on HDL-C quartiles. We used chi-square tests and Student’s t-tests or Mann-Whitney U tests to analyze categorical variables and continuous variables to compare differences between groups. Multivariate logistic regression analysis was used to study the association between HDL-C levels and the risk of chronic pain. Likelihood ratio tests were used to assess interactions between subgroups, and sensitivity analyses were conducted.ResultsOur final analysis included 4,688 participants, of which 733 (16.4%) had chronic pain. In the multivariate logistic regression model adjusted for covariates, there was a negative correlation between HDL-C levels and chronic pain. Specifically, for every 20 unit increase in HDL-C, the risk of chronic pain decreased by 26%. Compared with the lowest HDL-C quartile (< 43 mg/dL), the highest HDL-C quartile (≥ 64 mg/dL) was associated with a 24% reduction in the risk of chronic pain. No interaction factors affecting the relationship between HDL-C and chronic pain were found in the subgroup analysis.ConclusionThis study demonstrates a negative association between HDL-C levels and chronic pain in US adults, providing insights into the pathogenesis of chronic pain and potential improvements in chronic pain management strategies.

ObjectiveThe recent World Endoscopy Organization (WEO) guidelines now recognize precursor lesions of colorectal cancer (CRC) as legitimate screening targets. However, an optimal screening method for detecting advanced adenoma (AA), a significant precursor lesion, remains elusive.MethodsWe employed five machine learning methods, using clinical and laboratory data, to develop and validate a diagnostic model for identifying patients with AA (569 AAs vs. 3228 controls with normal colonoscopy). The best-performing model was selected based on sensitivity and specificity assessments. Its performance in recognizing adenoma-carcinoma sequence was evaluated in line with guidelines, and adjustable thresholds were established. For comparison, the Fecal Occult Blood Test (FOBT) was also selected.ResultsThe XGBoost model demonstrated superior performance in identifying AA, with a sensitivity of 70.8% and a specificity of 83.4%. It successfully detected 42.7% of non-advanced adenoma (NAA) and 80.1% of CRC. The model-transformed risk assessment scale provided diagnostic performance at different positivity thresholds. Compared to FOBT, the XGBoost model better identified AA and NAA, however, was less effective in CRC.ConclusionThe XGBoost model, compared to FOBT, offers improved accuracy in identifying AA patients. While it may not meet the recommendations of some organizations, it provides value for individuals who are unable to use FOBT for various reasons.

Emerging evidence suggests a link between γ-glutamyl transferase (GGT) and various malignancies. However, the relationship between GGT and advanced colorectal adenoma, a critical precursor to colorectal cancer, remains unclear. This study aimed to elucidate this relationship. We conducted a single-center retrospective study from April 2015 to June 2022, enrolling 3534 inpatients including 525 cases and 3009 controls. Data were extracted from the electronic medical records, encompassing clinicodemographic characteristics, co-morbidities, and several blood biochemical indicators. Utilizing logistic regression and curve fitting, we explored the relationship between GGT and advanced colorectal adenoma. After adjustment for confounding factors, we found that for each 20-unit increase in GGT, the risk of advanced colorectal adenoma increased by 6% (OR= 1.06 [1.01–1.12]). Moreover, individuals with high GGT levels (≥50 U/L) had a 61% higher risk of advanced colorectal adenoma compared to those with low GGT levels (

Abstract Β2-microglobulin (β2-M) is associated with various malignancies. However, the relationship between β2-M and colorectal cancer (CRC) remains unclear. We explored the association between β2-M and CRC among inpatients who underwent colonoscopy and explored factors that may modify the association. All consecutive inpatients who underwent colonoscopy were enrolled in a tertiary hospital between April 2015 and June 2022. Inpatients with initial CRC or normal colonoscopies were considered eligible as cases or controls, respectively. Baseline characteristics and laboratory indicators of the participants were collected from electronic medical records. Logistic regression analysis, smooth curve fitting, sensitivity analysis, and subgroup analysis were conducted in the present study. After adjusting for baseline clinical characteristics and laboratory parameters, β2-M was positively associated with CRC (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.11–1.58) among inpatients. When the β2-M level was assigned as tertiles, participants in the highest tertile presented with a higher risk of CRC (OR 2.33; 95% CI 1.57–3.48). A positive linear association was observed between β2-M and CRC with smooth curve fitting. In particular, it may be of great importance to monitor β2-M levels for predicting CRC patients.

Accurate estimation of the State of Health (SOH) of lithium-ion batteries is crucial for ensuring their safe and reliable operation. Data-driven methods have shown excellent performance in estimating SOH, but obtaining high-quality and strongly correlated features remains a major challenge for these methods. Moreover, different features have varying importance in both spatial and temporal scales, and single data-driven models are unable to capture this information, leading to issues with attention dispersion. In this paper, we propose a data-driven method for SOH estimation leveraging the Bi-directional Long Short-Term Memory (Bi-LSTM) that uses the Differential Thermal Voltammetry (DTV) analysis to extract features, and incorporates attention mechanisms (AM) at both temporal and spatial scales to enable the model focusing on important information in the features. The proposed method is validated using the Oxford Battery degradation Dataset, and the results show that it achieves high accuracy and robustness in SOH estimation. The Root Mean Squared Error (RMSE) and Mean Absolute Error (MAE) are around 0.4% and 0.3%, respectively, indicating the potential for online application of the proposed method in the cyber hierarchy and interactional network (CHAIN) framework.

The present study was to explore the association between lipoprotein(a) [Lp(a)] and colorectal cancer (CRC) among inpatients. This study included 2822 participants (393 cases vs. 2429 controls) between April 2015 and June 2022. Logistic regression models, smooth curve fitting, and sensitivity analyses were performed to investigate the relationship between Lp(a) and CRC. Compared with the lower Lp(a) quantile 1 (

Abstract Cisplatin (DDP) is a common therapeutic option for non‐small cell lung carcinoma (NSCLC). However, some patients fail to respond to the DDP chemotherapy. Therefore, identifying novel biomarkers to improve the diagnosis and treatment of NSCLC is important. Ubiquitin‐specific protease (USP14) is involved in various pathological conditions including cancer; however, the role of USP14 in NSCLC remains elusive. The SELEX technology was used to identify aptamers that specifically recognize DDP‐resistant lung cancer cells and couple them with nano‐zinc (zinc hydroxide, Zn(OH)2) carriers. USP14 levels were higher in DDP‐resistant lung cancer compared to DDP‐sensitive lung cancer. The survival rate of lung cancer patients with increased USP14 expression was significantly lower than the survival rate of patients with low USP14 expression. Silencing USP14 increased the tumor antagonistic action of DDP in A549 cisplatin‐resistant (A549/DDP) cells, while USP14 overexpression decreased the antagonist effects. Aptamer‐targeted nano‐zinc carriers were loaded with USP14 siRNA to target DDP‐resistant lung cancer cells. Aptamer‐targeted nano‐zinc carriers containing USP14 siRNA increased the antitumor effects of DDP in A549/DDP cells and mice bearing A549/DDP cells. These results indicate that aptamer‐guided nano‐zinc carriers may be a potent carrier for the precise treatment of drug‐resistant tumors.

Abstract The proliferation of Internet-of-Things has promoted a wide variety of emerging applications that require compact, lightweight, and low-cost optical spectrometers. While substantial progresses have been made in the miniaturization of spectrometers, most of them are with a major focus on the technical side but tend to feature a lower technology readiness level for manufacturability. More importantly, in spite of the advancement in miniaturized spectrometers, their performance and the metrics of real-life applications have seldomly been connected but are highly important. This review paper shows the market trend for chip-scale spectrometers and analyzes the key metrics that are required to adopt miniaturized spectrometers in real-life applications. Recent progress addressing the challenges of miniaturization of spectrometers is summarized, paying a special attention to the CMOS-compatible fabrication platform that shows a clear pathway to massive production. Insights for ways forward are also presented.

Abstract Background The aim of this prospective, pilot, single‐arm phase II trial was to evaluate the safety and efficacy of anlotinib combined with etoposide and platinum‐based regimens in the first‐line treatment of extensive‐stage small cell lung cancer (ES‐SCLC). Methods This phase II study was conducted at Fudan University Shanghai Cancer Center between December 2018 and December 2020. All patients received standard chemotherapy (etoposide plus cisplatin/carboplatin) consisting of four courses and anlotinib at 12 mg once per day for 2 weeks followed by a one‐week rest. Anlotinib administration was continued until disease progression, intolerable adverse events (AEs) or patient withdrawal from the study. The primary outcome measure was progression‐free survival (PFS). The secondary outcome measures were overall survival (OS), objective control rate (ORR), disease control rate (DCR) and AEs. Results Thirty‐seven patients were included in this study, and 30 patients were eligible for efficacy analysis. ORR and DCR were 90.0% and 96.7%, respectively. The estimated PFS and OS were 6.0 months (95% CI: 1.1–11.9 months) and 14.0 months (95% CI: 8.6–19.4 months), respectively. No unexpected adverse effects were reported. Hypertension (20/37, 54.1%), anemia (16/37, 43.2%), alopecia (15/37, 40.5%), elevated transaminases (9/37, 24.3%) and alkaline phosphatase (9/37, 24.3%) were the most commonly reported AEs. Thirteen patients (35.1%) reported grade 3–5 AEs. No treatment‐related deaths occurred during this study. Conclusion The addition of anlotinib to standard etoposide/platinum chemotherapy achieved encouraging PFS and OS in previously untreated ES‐SCLC patients, with an acceptable tolerability profile and no new safety signals observed.

ObjectiveThis study was to explore the relationship between fibrinogen and advanced colorectal adenoma among inpatients.MethodsFrom April 2015 to June 2022, 3738 participants (566 case subjects and 3172 control subjects) who underwent colonoscopies enrolled, and smooth curve fitting and logistic regression models were applied to explore the association between fibrinogen and advanced colorectal adenoma. In addition, sensitivity and subgroup analyses were performed to assess the stability of the results.ResultsCompared with lower fibrinogen quantile 1 (< 2.4 g/L), the adjusted OR values for fibrinogen and advanced colorectal adenoma in quantile 2 (2.4–2.75 g/L), quantile 3 (2.76–3.15 g/L), and quantile 4 (≥3.16 g/L) were 1.03 (95% confidence interval [CI]: 0.76–1.41), 1.37 (95% CI: 1.01–1.85), and 1.43 (95% CI: 1.06–1.94), respectively. A linear relationship between fibrinogen and advanced colorectal adenoma was observed. Sensitivity and subgroup analyses showed stable results.ConclusionComplements the evidence that fibrinogen was positively associated with advanced adenomas, suggesting that fibrinogen may play a role in the adenoma-carcinoma sequence.

Abstract During mid‐July 2021, an extreme heavy rainfall event (HRE) occurred in Henan Province (hereafter “21.7” HRE), with extreme hourly precipitation of 201.9 mm appearing at Zhengzhou station. Our preliminary analyses of the “21.7” HRE using the observations and ECMWF (European Centre for Medium‐Range Weather Forecasts) ERA5 reanalysis data, reached the following conclusions. Favorable configurations of various synoptic weather systems (e.g., strong upper‐level high‐pressure ridge, intense middle‐level low‐pressure trough) acted as crucial background conditions for the occurrence of the “21.7” HRE. A 21‐h long‐lived mesoscale convective vortex (MCV), mainly located in the middle and lower troposphere west of Zhengzhou city, was a key system that produced the extreme hourly rainfall of 201.9 mm·h−1. The MCV's development/sustainment was dominated by the vertical transport of cyclonic vorticity and tilting, as well as the horizontal import of cyclonic vorticity to the vortex's key region. In contrast, the divergence‐related vertical shrinking was the most detrimental factor. Lagrangian moisture transport analysis showed that moisture for the extreme heavy rainfall in Zhengzhou on July 20 mainly came from levels below 2200 m, driven by airflows on the peripheries of tropical cyclones IN‐FA and CEMPAKA. To enhance the understanding of “21.7” HRE, we suggest more in‐depth investigations in the future.

Abstract Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the main factor that leads to the deterioration of the disease. Currently, the diagnosis of AECOPD mainly relies on clinical manifestations, good predictors or biomarkers are lacking. We aim to reveal specific biomarkers and potential pathogenesis of AECOPD and provide a research basis for the diagnosis and treatment. Methods Four patients with AECOPD, four patients with stable COPD, and five control subjects were enrolled for RNA sequencing and KEGG analysis. The mRNA level of target genes was verified by quantitative real-time PCR (qPCR) with an expanded sample size (30 patients with AECOPD, 27 patients with stable COPD, and 35 control subjects). ELISA and immunofluorescence were used to identify the target proteins. Furthermore, the expression and function of WNT/β-catenin signaling pathway were assessed in animal models of COPD. Results RNA sequencing showed that 54 genes were up-regulated and 111 genes were down-regulated in the AECOPD. Differentially expressed genes were mainly enriched in WNT signaling pathway, et al. QPCR revealed that multi-genes of the WNT/β-catenin signaling were significantly down-regulated in AECOPD (P

Introduction: Transmembrane protein 16A (TMEM16A) is a Ca2+-activated chloride channel that plays a role in cancer cell proliferation, migration, invasion, and metastasis. However, whether TMEM16A contributes to breast cancer metastasis remains unknown. Objective: In this study, we investigated whether TMEM16A channel activation by ROCK1/moesin promotes breast cancer metastasis. Methods: Wound healing assays and transwell migration and invasion assays were performed to study the migration and invasion of MCF-7 and T47D breast cancer cells. Western blotting was performed to evaluate the protein expression, and whole-cell patch clamp recordings were used to record TMEM16A Cl− currents. A mouse model of breast cancer lung metastasis was generated by injecting MCF-7 cells via the tail vein. Metastatic nodules in the lung were assessed by hematoxylin and eosin staining. Lymph node metastasis, overall survival, and metastasis-free survival of breast cancer patients were assessed using immunohistochemistry and The Cancer Genome Atlas dataset. Results: TMEM16A activation promoted breast cancer cell migration and invasion in vitro as well as breast cancer metastasis in mice. Patients with breast cancer who had higher TMEM16A levels showed greater lymph node metastasis and shorter survival. Mechanistically, TMEM16A promoted migration and invasion by activating EGFR/STAT3/ROCK1 signaling, and the role of the TMEM16A channel activity was important in this respect. ROCK1 activation by RhoA enhanced the TMEM16A channel activity via the phosphorylation of moesin at T558. The cooperative action of TMEM16A and ROCK1 was supported through clinical findings indicating that breast cancer patients with high levels of TMEM16A/ROCK1 expression showed greater lymph node metastasis and poor survival. Conclusion: Our findings revealed a novel mechanism underlying TMEM16A-mediated breast cancer metastasis, in which ROCK1 increased TMEM16A channel activity via moesin phosphorylation and the increase in TMEM16A channel activities promoted cell migration and invasion. TMEM16A inhibition may be a novel strategy for treating breast cancer metastasis.

ObjectiveTo evaluate the performance and validate the diagnostic value of a nucleotide matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) with the analysis process optimized in identification of mycobacterium species.MethodsThe optimized analysis process was used for mycobacterial identification in the nucleic MALDI-TOF-MS. 108 samples were used for assessing the performance of nucleic MALDI-TOF-MS, including 25 reference standards, 37 clinical isolates, 37 BALF, and 9 plasmids. The BALF of 38 patients suspected of pulmonary mycobacterial infection was collected for validation. Clinical etiological diagnosis was used as the gold standard to evaluate the diagnostic value of nucleotide MALDI-TOF-MS.ResultsThe sensitivity, specificity, and accuracy of the nucleotide MALDI-TOF-MS in mycobacterial identification were 96.91%, 100% and 97.22%, respectively, and the limit of detection for mycobacterium tuberculosis (MTB) was 50 bacteria/mL. Among 38 patients suspected of pulmonary mycobacterial infection, 33 were diagnosed with pulmonary tuberculosis infection, and 5 with non-mycobacterial infection. In clinical validation, the positive rates of MALDI-TOF-MS, Xpert MTB/RIF, culture and AFS in BALF of patients diagnosed with tuberculosis infection were 72.7%, 63.6%, 54.5% and 27.3%, respectively. The sensitivity/specificity of MALDI-TOF-MS, Xpert, culture and AFS in diagnosing MTB were 72.7%/100%, 63.6%/100%, 54.5%/100%, 27.3%/100%, with the areas under the curve of 0.864, 0.818, 0.773, and 0.636, respectively.ConclusionOptimized nucleotide MALDI-TOF-MS has satisfactory sensitivity, specificity and low LOD in the identification of mycobacteria, which may serve as a potential assay for mycobacterial identification.

BackgroundThe association between hematologic parameters and anti-programmed death-1 (PD-1) inhibitors was generally examined without considering therapy lines and medicine types. The study was aimed to identify potential hematologic biomarkers associated with clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with first-line pembrolizumab and subsequent-line nivolumab.Materials and methods161 NSCLC patients were categorized into first-line pembrolizumab group (pembrolizumab group) and subsequent-line nivolumab group (nivolumab group). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of hematologic parameters for clinical outcomes.ResultsThe median progression-free survival (mPFS) was 9.6 months in the pembrolizumab group and 4.1 months in the nivolumab group (HR =1.61; P = 0.012); the median overall survival (mOS) was not reached in the pembrolizumab group and 17.7 months in the nivolumab group (HR =1.37; P = 0.23). Of the 79 patients in the pembrolizumab group, baseline PD-L1 tumor proportion score (TPS)≥1% was an independent factor of longer PFS and OS. Age≥60 years, absolute platelet count (APC)≥220×109/L and platelet-to-lymphocyte ratio (PLR)≥120 were associated with inferior PFS. Of the 82 patients in the nivolumab group, absolute neutrophil count (ANC)≥3×109/L was associated with longer PFS, while LDH (lactate dehydrogenase)≥160 U/L was associated with inferior PFS and derived neutrophil-to-lymphocyte ratio (dNLR)≥1.2 was associated with longer OS.ConclusionOur study identified multiple clinically accessible prognostic biomarkers in the peripheral blood in both the pembrolizumab and nivolumab subgroups.

Safety issues are one of the main limitations for further application of lithium-ion batteries, and battery degradation is an important causative factor. However, current state-of-health (SOH) estimation methods are mostly developed for a single feature and a single operating condition as well as a single battery material system, which consequently makes it difficult to guarantee robustness and generalization. This paper proposes a data-driven and multi-feature collaborative SOH estimation method based on equal voltage interval discharge time, incremental capacity (IC) and differential thermal voltammetry (DTV) analysis for feature extraction. The deep learning model is constructed based on bi-directional long short-term memory (Bi-LSTM) with the addition of attention mechanism (AM) to focus on the important parts of the features. The proposed method is validated based on a NASA dataset and Oxford University dataset, and the results show that the proposed method has high accuracy and strong robustness. The estimated root mean squared error (RMSE) are below 0.7% and 0.3%, respectively. Compared to single features, the collaboration between multiple features and AM resulted in a 25% error improvement, and the capacity rebound is well captured. The proposed method has the potential to be applied online in an end-cloud collaboration system.

Strengthening regulations on carbon emissions from ships is important for ensuring that China can achieve its dual carbon aims of reaching peak carbon emissions before 2030 and achieving carbon neutrality before 2060. Currently, the primary means of monitoring ship exhaust emissions are the sniffing method and non-imaging optical remote sensing; however, these methods suffer from a low prediction efficiency and high cost. We developed a method for predicting the CO2 content of ship exhaust that uses a convolutional neural network and mid-infrared spectral images. First, a bench experiment was performed to synchronously obtain mid-wave infrared spectral images of the ship exhaust plume and true values for the CO2 concentration from the online monitoring of eight spectral channels. Then, the ResNet50 residual neural network, which is suitable for image prediction tasks, was selected to predict the CO2 content. The preprocessed mid-infrared spectral image of each channel and the corresponding true value for the CO2 content were input to the neural network, and convolution was applied to extract the radiation characteristics. The neural network then mapped the relationship between the true CO2 content and the radiation characteristics for each channel, which it used to predict the CO2 content in the ship exhaust. The results demonstrated that the predicted and true CO2 contents had a root mean square error of 2 content of ship exhaust based on convolutional neural networks and mid-infrared spectral images is feasible and has reference significance for the remote monitoring of ship exhaust emissions.

Abstract Background In nonneutropenic patients with underlying respiratory diseases (URD), invasive pulmonary aspergillosis (IPA) is a life-threatening disease. Yet establishing early diagnosis in those patients remains quite a challenge. Methods A retrospective series of nonneutropenic patients with probable or proven IPA were reviewed from January 2014 to May 2018 in Department of Respiratory Medicine of two Chinese hospitals. Those patients were suspected of IPA and underwent lung computed tomography (CT) scans twice within 5–21 days. The items required for IPA diagnosis were assessed by their host factors, mycological findings and CT scans according to the European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria (EORTC/MSG criteria). Results Together with the risk factors, mycological findings and nonspecific radiological signs on first CT, ten patients were suspected of IPA. With the appearance of cavities on second CT scan in the following days, all patients met the criteria of probable or possible IPA. Except one patient who refused antifungal treatment, nine patients received timely antifungal treatment and recovered well. One of the nine treated IPA cases was further confirmed by pathology, one was confirmed by biopsy. Conclusions Dynamic monitor of CT scan provided specific image evidences for IPA diagnosis. This novel finding might provide a noninvasive and efficient strategy in IPA diagnosis with URD.

Sphingosine-1-phosphate lyase is encoded by the Sgpl1 gene, degrades S1P, and is crucial for S1P homeostasis in animal models and humans. S1P lyase deficient patients suffer from adrenal insufficiency, severe lymphopenia, and skin disorders. In this study, we used random mutagenesis screening to identify a mouse line carrying a missense mutation of Sgpl1 (M467K). This mutation caused similar pathologies as Sgpl1 knock-out mice in multiple organs, but greatly preserved its lifespan, which M467K mutation mice look normal under SPF conditions for over 40 weeks, in contrast, the knock-out mice live no more than 6 weeks. When treated with Imiquimod, Sgpl1M467K mice experienced exacerbated skin inflammation, as revealed by aggravated acanthosis and orthokeratotic hyperkeratosis. We also demonstrated that the IL17a producing Vγ6+ cell was enriched in Sgpl1M467K skin and caused severe pathology after imiquimod treatment. Interestingly, hyperchromic plaque occurred in the mutant mice one month after Imiquimod treatment but not in the controls, which resembled the skin disorder found in Sgpl1 deficient patients. Therefore, our results demonstrate that Sgpl1M467K point mutation mice successfully modeled a human disease after being treated with Imiquimod. We also revealed a major subset of γδT cells in the skin, IL17 secreting Vγ6 T cells were augmented by Sgpl1 deficiency and led to skin pathology. Therefore, we have, for the first time, linked the IL17a and γδT cells to SPL insufficiency.

The decadal variability of the summer extreme precipitation over southern China (EPSC) is remarkable, especially for the significant decadal enhancement after the 1990s. The study documented that the summer sea surface temperature (SST) over the North Atlantic and spring sea ice concentration (SIC) over the East Siberian Sea can significantly affect the EPSC. The summer SST over the North Atlantic influences the low-pressure cyclone in the western Pacific by modulating the SST over the tropical Pacific, thus affecting EPSC. A decrease in the SIC of the East Siberian Sea induces a negative Arctic Oscillation, which induces the increased SST over northwest Pacific and the anomalous cyclone over there, in turn, affecting EPSC. Both predictors have a quasi-period of 10–14 years, which provides useful predictive signals for EPSC. The leading 7-year SST and the leading 5-year SIC are chosen to establish the prediction model based on the decadal increment method, which can well predict the EPSC, especially for the shift in the early 1990s. These results provide a clue to the limited predictability of decadal-scale extreme climate events.

Compact and low‐cost spectropolarimeters are desirable in many fields for probing the wavelength‐dependent polarization state of light. Conventional spectropolarimetry systems use bulky, free‐space optical components or require at least four spectrometers. Herein, a chip‐scale spectropolarimeter capable of reconstructing input Stokes spectrum with a single spectrometer is demonstrated. All the components, including a surface polarization splitter, a channeled spectrum generator, and a Vernier spectrometer, are monolithically integrated on a footprint of 0.3 mm × 1.5 mm. The device is implemented using a complementary metal oxide semiconductor (CMOS)‐compatible fabrication process and achieves a resolution of 0.1 nm across a wavelength range of 56 nm near 1550 nm. This work provides a path toward on‐chip, low‐cost Stokes spectroscopy.

Abstract Background The preponderance of the evidence supports no association between traditional cardiovascular risk factors and venous thromboembolism (VTE), other than obesity. There are limited data in older people. Objectives To investigate whether cardiovascular risk factors (body mass index, smoking, alcohol intake, hypertension, and diabetes) are associated with the risk of VTE in elderly and to assess the combined effect between cardiovascular risk factors and genetic risk factors for VTE (factor V Leiden/prothrombin 20210A, positive family history of VTE, and non‐O blood group). Methods The Age and Thrombosis, Acquired and Genetic risk factors in the Elderly study is a multicenter case‐control study performed in Vermont, USA and Leiden, the Netherlands, comprising 401 cases with first VTE and 431 control subjects, all aged ≥70 years. To assess the risk of VTE, odds ratios (OR) with 95% confidence intervals (CIs) were calculated, adjusting for potential confounders. Results Both height and weight were positively associated with VTE risk: the ORs were 2.2 (95% CI, 1.2–3.9) and 1.5 (95% CI, 1.0–2.4) in the top quartile for height and weight separately. This risk was more pronounced for unprovoked VTE. Smoking, alcohol intake, and diabetes were not associated with VTE. Higher systolic and diastolic blood pressure and hypertension were associated with a decreased risk of VTE. In the presence of a genetic predisposition, height and weight further increased the risk of VTE. Conclusions In the elderly, height and weight are positively associated with the risk of VTE. With genetic predisposition, higher levels of height and weight further increase the risk of VTE.

Fat greenling (Hexagrammos otakii) is a kind of economic fish that is widely consumed by human, and its intensive farming technology is making important progress. However, high-density farming may cause the occurrence of diseases in H. otakii. Cinnamaldehyde (CNE) is a new feed additive for aquatic animals and has a positive effect on disease resistance. In the study, dietary CNE was evaluated on the growth performance, digestion, immune response, and lipid metabolism of juvenile H. otakii (6.21±0.19 g). Six experimental diets were formulated containing CNE at levels of 0, 200, 400, 600, 800, and 1000 mg/kg for 8 weeks. The percent weight gain (PWG), specific growth rate (SGR), survival (SR), and feeding rate (FR) were significantly increased by including CNE in fish diets regardless of the inclusion level (P

TMEM16A Ca2+-activated Cl− channels are expressed in pancreatic acinar cells and participate in inflammation-associated diseases. Whether TMEM16A contributes to the pathogenesis of acute pancreatitis (AP) remains unknown. Here, we found that increased TMEM16A expression in the pancreatic tissue was correlated with the interleukin-6 (IL-6) level in the pancreatic tissue and in the serum of a cerulein-induced AP mouse model. IL-6 treatment promoted TMEM16A expression in AR42J pancreatic acinar cells via the IL-6 receptor (IL-6R)/signal transducers and activators of transcription 3 (STAT3) signaling pathway. In addition, TMEM16A was co-immunoprecipitated with the inositol 1,4,5-trisphosphate receptor (IP3R) and was activated by IP3R-mediated Ca2+ release. TMEM16A inhibition reduced the IP3R-mediated Ca2+ release induced by cerulein. Furthermore, TMEM16A overexpression activated nuclear factor-κB (NFκB) and increased IL-6 release by increasing intracellular Ca2+. TMEM16A knockdown by shRNAs reduced the cerulein-induced NFκB activation by Ca2+. TMEM16A inhibitors inhibited NFκB activation by decreasing channel activity and reducing TMEM16A protein levels in AR42J cells, and it ameliorated pancreatic damage in cerulein-induced AP mice. This study identifies a novel mechanism underlying the pathogenesis of AP by which IL-6 promotes TMEM16A expression via IL-6R/STAT3 signaling activation, and TMEM16A overexpression increases IL-6 secretion via IP3R/Ca2+/NFκB signaling activation in pancreatic acinar cells. TMEM16A inhibition may be a new potential strategy for treating AP. Keywords: TMEM16A, Inositol 1,4,5-trisphosphate receptor, Acute pancreatitis, NFκB, Interleukin-6

In order to explore the application of the precision extracoronal attachment based on three-dimensional finite element stress model in the repair of unilateral mandibular dissociation and loss, the stress distribution of the butment and periodontal tissues when the precision extracoronal attachment was used in unilateral mandibular dissociation and loss was analyzed, so as to provide reference for the application of materials in clinical repair. In this study, the biomechanics of oral cavity and its attachment were analyzed to provide theoretical basis for model construction. Because the degree of periodontal tissue absorption and the number of abutment teeth affected the restoration effect of the coronal precision attachment, the models were established from these two perspectives. The results showed that when the periodontal tissue absorption of both abutment teeth exceeded 1/3, the method of double abutment restoration was not recommended. When three abutments were used, there was a significant decrease compared with the absorption of the periodontal tissue of the double abutment. In clinic, the stress distribution of the distal abutment teeth and its periodontal tissues can be improved by increasing the number of abutment tooth. However, since increasing the number of abutments required an increase in the amount of healthy tooth tissue, it couldn’t be blindly selected in the clinic. After comprehensive consideration, it is appropriate to choose two abutment teeth for restoration. Keywords: Precision extracoronal attachment, Unilateral dissociation and loss, Abutment tooth, Periodontal tissue, Stress model

Raman spectroscopy has been efficiently used to recognize breast cancer tissue by detecting the characteristic changes in tissue composition in cancerization. In addition to chemical composition, the change in bio-structure may be easily obtained via polarized micro-Raman spectroscopy, aiding in identifying the cancerization process and diagnosis. In this study, a polarized Raman spectral technique is employed to obtain rich structural features and, combined with deep learning technology, to achieve discrimination of breast cancer tissue. The results reconfirm that the orientation of collagen fibers changes from parallel to vertical during breast cancerization, and there are significant structural differences between cancerous and normal tissues, which is consistent with previous reports. Optical anisotropy of collagen fibers weakens in cancer tissue, which is closely related with the tumor’s progression. To distinguish breast cancer tissue, a discrimination model is established based on a two-dimensional convolutional neural network (2D-CNN), where the input is a matrix containing the Raman spectra acquired at a set of linear polarization angles varying from 0° to 360°. As a result, an average discrimination accuracy of 96.01% for test samples is achieved, better than that of the KNN classifier and 1D-CNN that are based on non-polarized Raman spectra. This study implies that polarized Raman spectroscopy combined with 2D-CNN can effectively detect changes in the structure and components of tissues, innovatively improving the identification and automatic diagnosis of breast cancer with label-free probing and analysis.

The contact characteristics of angular contact ball bearings are closely related to the thermal failure of high-speed spindle systems. This paper establishes a closed-loop iterative model for analyzing the ball–race contact characteristics of machine tool spindle bearings at different combined loads and oil supply temperatures, based on a five-degree-of-freedom quasi-static analysis model and the finite difference method. Additionally, the accuracy of the proposed model is verified by comparing the measured values of temperature rise with the predicted values. Based on the verification of the accuracy of the model, the contact characteristics of machine tool spindle bearings under strong asymmetric loads and high-temperature lubrication oil are discussed in detail. The results show that at elevated temperatures, the internal loads of angular contact ball bearings operating under combined loads become concentrated, which will lead to reduced fatigue life of the bearings and even thermal seizure.

BackgroundThe addition of bevacizumab or pembrolizumab to pemetrexed-platinum chemotherapy has produced significant clinical benefits to patients with untreated, advanced non-squamous non-small cell lung cancer (NSCLC) lacking targetable genetic aberrations. However, the direct comparison between these two first-line treatments needs to be investigated.MethodsWe retrospectively investigated the medical records of 102 patients with stage IIIB~IV non-squamous NSCLC, and without sensitizing EGFR/ALK/ROS1 alterations. All patients received pembrolizumab or bevacizumab plus pemetrexed-platinum chemotherapy as the first-line treatment between December 2018 to April 2021 at Fudan University Shanghai Cancer Center. Assessments included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). We also evaluated the prognostic biomarkers in the overall population and explored potential predictive biomarkers to aid the selection of optimal treatment regimens.ResultsThe median PFS was 10.0 months in the pembrolizumab group and 9.2 months in bevacizumab group (HR = 1.006; P = 0.982), while the median OS was not reached in either group (HR= 1.193; P =0.714). ORR was 36.7% versus 43.4% (P = 0.548) and DCR was 89.8% versus 92.5% (P = 0.735) in the pembrolizumab and bevacizumab groups, respectively. In the overall study population, baseline lymphocyte to monocyte ratio (LMR) >1.95 (HR = 0.312, P < 0.001) was an indicator of longer PFS. The presence of baseline bone metastasis (HR = 4.107, P = 0.009), baseline lactate dehydrogenase (LDH) >300 U/L (HR = 4.300, P = 0.025) and LMR ≤1.95 (HR = 5.291, P = 0.039) were associated with inferior OS. Baseline neutrophil-to-lymphocyte ratio (NLR) ≤3.10 was predictive of significantly favorable OS in the bevacizumab combination treatment (HR = 5.073, P = 0.039). The safety profiles were generally comparable between the two groups.ConclusionsIn patients with chemotherapy-naive, advanced, non-squamous NSCLC who lack driver mutations, the efficacy and safety of pembrolizumab and bevacizumab when combined with pemetrexed-platinum were comparable. For patients with baseline NLR ≤3.10, the bevacizumab combination therapy elicited significantly better OS benefits.

Calmodulin-binding proteins belong to the IQ67 domain (IQD) gene family and play essential roles in plant development and stress responses. However, the role of IQD gene family in potato (Solanum tuberosum L.) is yet to be known. In the present study, 23 StIQDs were identified in the potato genome and named StIQD1 to StIQD23. They were unevenly distributed on 10 of the 12 chromosomes. Phylogenetic analysis divided the IQDs into four subfamilies (IQD I–IV). StIQDs found in three of the four subfamilies. Synteny analysis confirmed that potato and tomato shared a close evolutionary relationship. Besides, RNA-Seq data analysis revealed that the expression of 19 of the 23 StIQDs was detected in at least one of the 12 tissues, and some of which showed a tissue-specific pattern. Quantitative reverse transcriptase–polymerase chain reaction results further confirmed that 14 StIQDs responded differently to various abiotic stresses, including drought, extreme temperature, and CaCl2 treatment, suggesting their significance in stress response. This study presents a comprehensive overview of the potato IQD gene family and lays a foundation for further analysis of the StIQDs functions in plant development and stress response.

Abstract Background A high D‐dimer level and parameters of the thrombin generation (TG) potential are associated with the risk of a first venous thrombosis (VT) in young and middle‐aged populations. Objectives To investigate whether D‐dimer and TG potential (lag‐time, time‐to‐peak [ttPeak], peak thrombin, endogenous thrombin potential [ETP], and velocity index), are associated with the risk of a first VT in those aged 70 years and older. Methods We included 215 patients with a first VT and 358 controls, all aged >70 years, from the Age and Thrombosis, Acquired and Genetic Risk Factors in the Elderly (AT‐AGE) study. To assess the risk of VT, odds ratios with 95% confidence intervals (CIs) were estimated using logistic regression analysis. Results D‐dimer and all TG parameters except lag time were associated with an increased risk of VT in a dose‐response manner. Comparing the fourth with the first quartile (for ttPeak comparing the first with the fourth quartile), risk estimates were: 7.8 (95% CI, 4.0‐15.0) for peak, 2.0 (95% CI, 1.2‐3.3) for ttPeak, 9.1 (95% CI, 4.4‐18.9) for ETP, and 11.5 (95% CI, 5.7‐23.3) for velocity index. Comparing the highest quartile of D‐dimer with the lowest, the risk was 7.7‐fold increased (95% CI, 4.0‐14.8). Furthermore, all factors also increased the risk of VT after dichotomizing at more extreme cutoff values. The risk of VT was further increased in the presence of multiple prothrombotic TG parameters and elevated D‐dimer level or in combination with prothrombotic mutations. Conclusions D‐dimer and TG parameters (except lag time) are associated with the risk of first VT in elderly population.

Fabrication of ultrathin organic semiconductor nanostructures with precise alignment, tuneable morphology and high crystallinity remains challenging. Here the authors use an assembly technique with dewetting process controllability for patterning organic single-crystal arrays in a sub-hundred nanometer space.

Frequency estimation of undersampled waveforms receives increasing attention in communication, radar signal processing, instrumentation and measurements, and so on. However, due to the lack of recognizing the correct remainder between two side spectra, the existing Chinese Remainder Theorem (CRT)-based frequency estimators can hardly deal with real-valued signals. To achieve this goal, this paper proposes an estimator combining spectrum correction (aiming to enhance reconstruction accuracy by incorporating the fractional parts of DFT remainders), closed-form CRT, and a remainder sifting approach. Based on the detection of an undersampled waveform's zero crossing point, this solution can pick out the correct remainder between two side spectra, which ensures that the CRT achieves a valid reconstruction. Compared with the existing Maroosi-Bizaki estimator, the proposed method not only enlarges the upper bound of frequency recovery but also possesses higher reconstruction accuracy (the relative error is less than 0.002%) with lower consumption of computational complexity. The numerical results verify the superior performances of our estimator.

To improve transportation efficiency, a supercritical CO2 pipeline is the best choice for large-scale and long-distance transportation inshore and offshore. However, corrosion of the pipe wall will occur as a result of the presence of free water and other impurities present during CO2 capture. Defects caused by corrosion can reduce pipe strength and result in pipe failure. In this paper, the burst pressure of subsea supercritical CO2 pipelines under high pressure is investigated. First, a mechanical model of corroded CO2 pipelines is established. Then, using the unified strength theory (UST), a new burst pressure equation for subsea supercritical CO2 pipelines is derived. Next, analysis of the material’s intermediate principal stress parameters is conducted. Lastly, the accuracy of the burst pressure equation of subsea supercritical CO2 pipelines is proven to meet the engineering requirement by experimental data. The results indicate that the parameter b of UST plays a significant role in determining burst pressure of pipelines. The study can provide a theoretical basis and reference for the design of subsea supercritical CO2 pipelines.

Although the blockade of the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway has become a promising treatment strategy for several types of cancers, the constitutive activation of c-Met in tumors may cause a low overall response rate to PD-1 inhibitors. Increasing evidence indicates that the dual inhibition of c-Met and PD-1 could improve the efficacy of anti-PD-1/PD-L1 monoclonal antibodies for tumor immunotherapy. In this study, we developed two bispecific single-chain diabodies targeting c-Met and PD-1 for the treatment of solid tumors based on protein homology modeling, and we identified that the binding affinity of diabody-mp to c-Met was 50-folds higher than that of diabody-pm. The results of in vitro studies revealed that both diabodies suppressed HGF-induced proliferation, migration, and invasion of tumor cells, inhibiting the activation of c-Met signaling by antagonizing HGF binding to c-Met. Moreover, they promoted T cell activation by blocking the PD-1 pathway, mediating tumor cellular cytotoxicity through T cell engagement. In vivo studies with mice models demonstrated that diabody-mp exhibited higher therapeutic efficacy than other structural antibodies, greatly enhancing the survival of c-Met-positive tumor-bearing mice compared to single or combined c-Met and PD-1 blockade therapy. Furthermore, diabody-mp, which had a higher c-Met binding affinity, showed better anti-tumoral activity than diabody-pm, which had a lower c-Met binding affinity. In conclusion, bispecific anti-PD-1/c-Met diabody-mp, with high c-Met-associated affinity, inhibited tumor growth by activating T cells, suggesting its therapeutic potential for c-Met-positive solid tumors.

Asthma in pregnancy is a health issue of great concern. Physiological changes and drug compliance during pregnancy can affect asthma control in varying degrees, and the control level of asthma and the side effects of asthma medications are closely related to the adverse perinatal outcomes of mother and fetus. This article provides an update on the available literature regarding the alleviating or aggravating mechanism of asthma in pregnancy, diagnosis, disease assessment, and systematic management, to provide a new guidance for physician, obstetric joint doctor, and health care practitioner.

The chiral signal of the carvone air/liquid interface is probed by heterodyne-detected sum frequency generation (HD-SFG) without the electronic resonance. The chiral SFG spectra exhibit two distinguishable spectral signatures. Four chiral vibrational peaks of the R- and S-carvone molecules are with opposite signs, which can directly determine the surface molecular chirality. Two achiral vibrational peaks are also observed with the same sign. The different spectral signatures can provide a detailed chirality characterization at the molecular interface.

Abstract Background Impaired T cell reconstitution remains a major deterrent in the field of bone marrow (BM) transplantation (BMT) due to pre-conditioning-induced damages inflicted to the thymi of recipient hosts. Given the previously reported thymo-stimulatory property of interleukin (IL)-21, we reasoned that its use post-BMT could have a profound effect on de novo T cell development. Methods To evaluate the effect of IL-21 on de novo T cell development in vivo, BM derived from RAG2p-GFP mice was transplanted into LP/J mice. Lymphocyte reconstitution was first assessed using a hematological analyzer and a flow cytometer on collected blood samples. Detailed flow cytometry analysis was then performed on the BM, thymus, and spleen of transplanted animals. Finally, the effect of human IL-21 on thymopoiesis was validated in humanized mice. Results Using a major histocompatibility complex (MHC)-matched allogeneic BMT model, we found that IL-21 administration improves immune reconstitution by triggering the proliferation of BM Lin−Sca1+c-kit+ (LSK) subsets. The pharmacological effect of IL-21 also culminates in the recovery of both hematopoietic (thymocytes) and non-hematopoietic (stromal) cells within the thymi of IL-21-treated recipient animals. Although T cells derived from all transplanted groups proliferate, secrete various cytokines, and express granzyme B similarly in response to T cell receptor (TCR) stimulation, full regeneration of peripheral naïve CD4+ and CD8+ T cells and normal TCRvβ distribution could only be detected in IL-21-treated recipient mice. Astonishingly, none of the recipient mice who underwent IL-21 treatment developed graft-versus-host disease (GVHD) in the MHC-matched allogeneic setting while the graft-versus-tumor (GVT) effect was strongly retained. Inhibition of GVHD onset could also be attributed to the enhanced generation of regulatory B cells (B10) observed in the IL-21, but not PBS, recipient mice. We also tested the thymopoiesis-stimulating property of human IL-21 in NSG mice transplanted with cord blood (CB) and found significant improvement in de novo human CD3+ T cell development. Conclusions In sum, our study indicates that IL-21 represents a new class of unforeseen thymopoietin capable of restoring thymic function following BMT.

Multiuser transmission with shared spectrum is investigated in the presence of energy harvesting. For each user, the data generation, the harvested energy arrival, and the channel state variation are, respectively, considered as stochastic processes. Each user aims to maximize its own average throughput. Accordingly, a stochastic game is formulated at first. Next, we analyze the stochastic game in infinite-stage and finite-stage scenarios, respectively. On the basis of theoretical studies, an iterated distributive algorithm with solving a linear problem in each iteration is designed for the infinite case. For the finite case, two distributed algorithms named CVPBI and GoPGA are proposed. Finally, the effectiveness of the proposed algorithms is demonstrated by simulations.

Raman spectroscopy has been widely used for quantitative analysis in biomedical and pharmaceutical applications. However, the signal-to-noise ratio (SNR) of Raman spectra is always poor due to weak Raman scattering. The noise in Raman spectral dataset will limit the accuracy of quantitative analysis. Because of high correlations in the spectral signatures, Raman spectra have the low-rank property, which can be used as a constraint to improve Raman spectral SNR. In this paper, a simple and feasible Raman spectroscopic analysis method by Low-Rank Estimation (LRE) is proposed. The Frank-Wolfe (FW) algorithm is applied in the LRE method to seek the optimal solution. The proposed method is used for the quantitative analysis of pharmaceutical mixtures. The accuracy and robustness of Partial Least Squares (PLS) and Support Vector Machine (SVM) chemometric models can be improved by the LRE method.

At least 12% of human cancers are caused by virus infection. To understand whether other viruses are associated with human cancers, a viral metagenomics approach was used to analyze the composition of the viral communities of the serum of the patients with Hodgkin’s lymphoma (HL) and non-Hodgkin lymphoma. In this report, a human anellovirus TTMV named TTMV-SH was discovered from three patients with HL. The complete genome of TTMV-SH is 2812nt in length. Phylogenetic analysis based on ORF1 indicated that TTMV-SH of the 11 isolates cluster with TTMV strain TLMV-CBD231 sharing only 60.3–62% sequence similarity, and the sequences divergence is 41.5–43.1%, which indicates that TTMV-SH is a novel species. The TTMV-SH prevalence in HL group, especially in nodular sclerosing Hodgkin’s lymphomas (NSHL), was significantly higher than in the healthy group implicated that the TTMV-SH may be associated with HL, especially NSHL.