sRNA expression profile of KPC-2-producing carbapenem-resistant Klebsiella pneumoniae: Functional role of sRNA51.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has significant challenges to human health and clinical treatment, with KPC-2-producing CRKP being the predominant epidemic strain. Therefore, there is an urgent need to identify new therapeutic targets and strategies. Non-coding small RNA (sRNA) is a post-transcriptional regulator of genes involved in important biological processes in bacteria and represents an emerging therapeutic strategy for antibiotic-resistant bacteria. In this study, we analyzed the transcription profile of KPC-2-producing CRKP using RNA-seq. Of the 4693 known genes detected, the expression of 307 genes was significantly different from that of carbapenem-sensitive Klebsiella pneumoniae (CSKP), including 133 up-regulated and 174 down-regulated genes. Both the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly related to metabolism. In addition, we identified the sRNA expression profile of KPC-2-producing CRKP for the first time and detected 115 sRNAs, including 112 newly discovered sRNAs. Compared to CSKP, 43 sRNAs were differentially expressed in KPC-2-producing CRKP, including 39 up-regulated and 4 down-regulated sRNAs. We chose sRNA51, the most significantly differentially expressed sRNA in KPC-2-producing CRKP, as our research subject. By constructing sRNA51-overexpressing KPC-2-producing CRKP strains, we found that sRNA51 overexpression down-regulated the expression of acrA and alleviated resistance to meropenem and ertapenem in KPC-2-producing CRKP, while overexpression of acrA in sRNA51-overexpressing strains restored the reduction of resistance. Therefore, we speculated that sRNA51 could affect the resistance of KPC-2-producing CRKP by inhibiting acrA expression and affecting the formation of efflux pumps. This provides a new approach for developing antibiotic adjuvants to restore the sensitivity of CRKP.

Toe stimulation improves tactile perception of the genitals.

The human body is represented in a topographic pattern in the primary somatosensory cortex (S1), and genital representation is displaced below the toe representation. However, the relationship between the representation of the genitals and toe in S1 remains unclear. In this study, tactile stimulation was applied to the big toe in healthy subjects to observe changes in tactile acuity in the unstimulated genital area, abdomen, and metacarpal dorsal. Then tactile stimulation was applied to the right abdomen and metacarpal dorsal to observe changes in tactile acuity in bilateral genitals. The results revealed that tactile stimulation of the big toe led to a reduction in the 2-point discrimination threshold (2PDT) not only in the stimulated big toe but also in the bilateral unstimulated genitals, whereas the bilateral abdomen and metacarpal dorsal threshold remained unchanged. On the other hand, tactile stimulation of the abdomen and metacarpal dorsal did not elicit 2-point discrimination threshold changes in the bilateral genitals. Cortical and subcortical mechanisms have been proposed to account for the findings. One explanation involves the intracortical interaction between 2 adjacent representations. Another possible explanation is that the information content of a specific body part is broadly distributed across the S1. Moreover, exploring the links between human behaviors and changes in the cerebral cortex is of significant importance.

Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

Clonal spread of blaNDM-1-carrying Salmonella enterica serovar Typhimurium clone ST34 and wide spread of IncHI2/ST3-blaNDM-5 plasmid in China.

OBJECTIVES: To characterize blaNDM-carrying Salmonella recovered from a pig slaughterhouse. METHODS: In this study, 46 environment samples were collected from a slaughterhouse in China, and screened for carbapenem-resistant Enterobacterales. WGS, antimicrobial susceptibility testing and conjugation experiments were carried out to identify the isolates' resistance phenotypes and genetic characteristics. The phylogenetic relatedness of the Salmonella isolates obtained in this study and Salmonella (ST34 and ST29) in GenBank was determined. RESULTS: Two ST34 Salmonella Typhimurium and one ST29 Salmonella Stanley, recovered from three environmental samples (6.52%), were positive for blaNDM-1 and blaNDM-5, respectively. The two ST34 S. Typhimurium strains exhibited a close relationship (10-36 SNPs) with two human-derived blaNDM-1-bearing isolates from China (Hong Kong and Guangxi Province) and two blaNDM-negative ST34 Salmonella strains from the UK. The blaNDM-1 genes were located on IncHI2/ST3 plasmids. The capture of blaNDM-1 by the IncHI2/ST3 plasmid seems to be due to homologous recombination mediated by circular structures, as the genetic arrangements of the blaNDM-1 gene contain two IS26 elements of the same orientation. The blaNDM-5 gene was also carried by the IncHI2/ST3 plasmid, which shares highly similar structures with other blaNDM-5-bearing IncHI2/ST3 plasmids from other sources (fish, chicken, duck, human). CONCLUSIONS: This is the first report of a blaNDM-5-carrying IncHI2/ST3 plasmid in Salmonella. The clonal spread of NDM-1-producing ST34 S. Typhimurium across human and animal-associated environments, and the widespread dissemination of epidemic blaNDM-5-carrying IncHI2/ST3 plasmids among Enterobacteriaceae in China indicate the potential of further dissemination of blaNDM among Salmonella, which poses a threat to public health.

Acidity-Triggered "Sticky Spotlight": CCK2R-Targeted TME-Sensitive NIR Fluorescent Probes for Tumor Imaging In Vivo.

Cancer which causes high mortality globally threatens public health seriously. There is an urgent need to develop tumor-specific near-infrared (NIR) imaging agents to achieve precise diagnosis and guide effective treatment. In recent years, imaging probes that respond to acidic environments such as endosomes, lysosomes, or acidic tumor microenvironments (TMEs) are being developed. However, because of their nonspecific internalization by both normal and tumor cells, resulting in a poor signal-to-noise ratio in diagnosis, these pH-sensitive probes fail to be applied to in vivo tumor imaging. To address this issue, a cholecystokinin-2 receptor (CCK2R)-targeted TME-sensitive NIR fluorescent probe R2SM was synthesized by coupling pH-sensitive heptamethine cyanine with a CCK2R ligand, minigastrin analogue 11 (MG11) for in vivo imaging, in which MG11 would target overexpressed CCK2Rs in gastrointestinal stromal tumors (GISTs). Cell uptake assay demonstrated that R2SM exhibited a high affinity for CCK2R, leading to receptor-mediated internalization and making probes finally accumulated in the lysosomes of tumor cells, which suggested in the tumor tissues, the probes were distributed in the extracellular acidic TME and intracellular lysosomes. With a pKa of 6.83, R2SM can be activated at the acidic TME (pH = 6.5-6.8) and lysosomes (pH = 4.5-5.0), exhibiting an apparent pH-dependent behavior and generating more intense fluorescence in these acidic environments. In vivo imaging showed that coupling of MG11 with a pH-sensitive NIR probe facilitated the accumulation of probe and enhanced the fluorescence in CCK2R-overexpressed HT-29 tumor cells. A high signal was observed in the tumor region within 0.5 h postinjection, indicating its potential application in intraoperative imaging. Fluorescence imaging of R2SM exhibited higher tumor-to-liver and tumor-to-kidney ratios (2.1:1 and 2.3:1, respectively), compared separately with the probes that are lipophilic, pH-insensitive, or MG11-free. In vitro and in vivo studies demonstrated that the synergistic effect of tumor targeting with pH sensitivity plays a vital role in the high signal-to-noise ratio of the NIR imaging probe. Moreover, different kinds of tumor-targeting vectors could be conjugated simultaneously with the NIR dye, which would further improve the receptor affinity and targeting efficiency.

Tunable non-polarizing optical bandpass filtering in prism pair coupled planar optical waveguide.

A tunable non-polarizing optical bandpass filter structure, comprising a prism pair coupled planar optical waveguide (POW), is demonstrated, by changing the incident angle of the filter. Experimental measurements show that pass bands for both TM and TE polarized waves are present in the filter simultaneously, and the two passbands overlap on each other. The overlapping of the two passbands can be sustainable for the peak wavelength from 623 to 852 nm as the incident angle of the light tuned within 2°. This POW based optical bandpass filter can be potentially applicable in various fields of optical and laser spectroscopies.

Camera calibration optimization algorithm that uses a step function.

Camera calibration is very important when planning machine vision tasks. Calibration may involve 3D reconstruction, size measurement, or careful target positioning. Calibration accuracy directly affects the accuracy of machine vision. The parameters in many image distortion models are usually applied to all image pixels. However, this may be associated with rather high pixel reprojection errors at image edges, compromising camera calibration accuracy. In this paper, we present a new camera calibration optimization algorithm that features a step function that splits images into center and edge regions. First, based on the increasing pixel reprojection errors according to the pixel distance away from the image center, we gave a flexible method to divide an image into two regions, center and boundary. Then, the algorithm automatically determines the step position, and the calibration model is rebuilt. The new model can calibrate the distortions at the center and boundary regions separately. Optimized by the method, the number of distortion parameters in the old model is doubled, and different parameters represent different distortions within two regions. In this way, our method can optimize traditional calibration models, which define a global model to describe the distortion of the whole image and get a higher calibration accuracy. Experimentally, the method significantly improved pixel reprojection accuracy, particularly at image edges. Simulations revealed that our method was more flexible than traditional methods.

Serotype distribution, antibiotic resistance, multilocus sequence typing, and virulence factors of invasive and non-invasive Streptococcus pneumoniae in Northeast China from 2000 to 2021.

Streptococcus pneumoniae infection is a major public health concern with high morbidity and mortality rates. This study aimed to evaluate the serotype distribution, antimicrobial resistance changes, clonal composition, and virulence factors of S. pneumoniae isolates causing pneumococcal disease in northeast China from 2000 to 2021. A total of 1,454 S. pneumoniae isolates were included, with 568 invasive strains and 886 non-invasive strains. The patients from whom the S. pneumoniae were isolated ranged in age from 26 days to 95 years, with those ≤ 5 years old comprising the largest group (67.19%). 19 F, 19 A, 23 F, 14, and 6B were the most common serotypes, of which 19 A and 19 F were the main serotypes of invasive and non-invasive S. pneumoniae, respectively. CC271 was the most common multilocus sequence type. Serotype 14 had the lowest expression of cbpA, rrgA, and psrP genes, but expression levels of 19 A and 19 F genes were similar. All isolates were sensitive to ertapenem, moxifloxacin, linezolid, and vancomycin but highly resistant to macrolides, tetracyclines, and cotrimoxazole. Simultaneous resistance to erythromycin, clindamycin, tetracyclines, and trimethoprim/sulfamethoxazole was common pattern among multidrug-resistant isolates. Non-invasive S. pneumoniae had higher resistance to ß-lactam antibiotics than invasive strains. 19 A and 19 F were the main strains of penicillin-resistant S. pneumoniae. The resistance rate of ß-lactam antibiotics decreased from 2017 to 2021 compared to previous periods. Including PCV13 in the national immunization program can reduce the morbidity and mortality rates of pneumococcal disease effectively.

Pectic oligosaccharides: enzymatic preparation, structure, bioactivities and application.

Pectic oligosaccharides have become novel bioactive components. However, the comprehensive preparation methods, structural features, bioactivities and application of them lack a systematic review. Here, we focused on the enzymatic preparation of pectic oligosaccharides, and attempted to outline relationships among the enzymolysis condition, structure, bioactivities and application of pectic oligosaccharides. Pectic oligosaccharides were characterized by the oligosaccharides with units of →4)-α-GalpA-(1→4)-α-GalpA-(1→ or →4)-α-GalpA-(1→2)-α-Rhap-(1→. Enzymatic method was the most suitable approach for pectic oligosaccharides preparation that was significantly affected by the enzyme's type, time and concentration. Besides, pectic oligosaccharides possessed various bioactivities including prebiotic, anti-glycosylation, antioxidant, anticancer and lipid metabolism-regulation activities, which were closely associated with the molecular weight, the structure of side chain and the monosaccharide composition. Especially, many pectic oligosaccharides with low molecular weight demonstrated high prebiotic activities, and those with arabinogalactan side chains exhibited strong anticancer activities. Moreover, pectic oligosaccharides have been used in food preservatives, dairy product additives and food processing aids. Nevertheless, the industrial application, novel technology exploration, and structure-bioactivity relationship of pectic oligosaccharides remain a demanding and significant task for future work.

A comparative study of general and severe mycoplasma pneumoniae pneumonia in children.

OBJECTIVES: The increasing prevalence of severe Mycoplasma pneumoniae pneumonia (SMPP) poses a significant threat to the health of children. This study aimed to characterise and assess the outcomes in children with SMPP. METHODS: We retrospectively analysed children hospitalised for M. pneumoniae pneumonia (MPP) between January and December 2022. Retrospectively, demographic, clinical, underlying diseases, laboratory and radiological findings, and treatment outcomes were collected and analysed. Disease severity was defined as severe or general according to the Guideline for diagnosis and treatment of community-acquired pneumonia in children (2019 version). RESULTS: Over a 12-month observation period, 417 children with MPP were enrolled, 50.6% (211/417) of whom had SMPP, with the peak incidence observed in winter. Of the 211 children with SMPP, 210 were treated and discharged with improvement, while one child with congenital heart disease died of cardioembolic stroke. A significantly higher proportion of patients with SMPP had underlying diseases, extrapulmonary complications (myocardial and digestive system involvement), and bacterial co-infection. A total of 25 (12%) children with SMPP received mechanical ventilation. The median duration of mechanical ventilation was 3 days. All children were treated with macrolide antibiotic. A significantly higher proportion of patients with SMPP received antibiotic other than macrolides, methylprednisolone sodium succinate, intravenous immunoglobulin and anticoagulation, compared with patients with general MPP (GMPP). Children with SMPP had significantly higher levels of white blood cells, neutrophil percentage, C-reactive protein, procalcitonin, interferon-γ, interleukin (IL)-2, IL-5, IL-6, IL-8, IL-10 and significantly lower percentages of lymphocytes, monocytes, and natural killer cells, compared with GMPP group. CONCLUSION: Our findings suggest that severely ill children have more pronounced inflammatory reaction and extrapulmonary complications. For effective management of children with SMPP, hormonal, prophylactic, anticoagulant therapy, as well as the use of antibiotics other than macrolides for bacterial co-infections, could be incorporated into treatment regimens.

Enhancement of Motor Learning and Corticospinal Excitability: The Role of Electroacupuncture and Motor Training in Healthy Volunteers.

BACKGROUND This study embarked on an innovative exploration to elucidate the effects of integrating electroacupuncture (EA) with motor training (MT) on enhancing corticospinal excitability and motor learning. Central to this investigation is the interplay between homeostatic and non-homeostatic metaplasticity processes, providing insights into how these combined interventions may influence neural plasticity and motor skill acquisition. MATERIAL AND METHODS The investigation enrolled 20 healthy volunteers, subjecting them to 4 distinct interventions to parse out the individual and combined effects of EA and MT. These interventions were EA alone, MT alone, EA-priming followed by MT, and MT-priming followed by EA. The assessment of changes in primary motor cortex (M1) excitability was conducted through motor-evoked potentials (MEPs), while the grooved pegboard test (GPT) was used to evaluate alterations in motor performance. RESULTS The findings revealed that EA and MT independently contributed to enhanced M1 excitability and motor performance. However, the additional priming with EA or MT did not yield further modulation in MEPs amplitudes. Notably, EA-priming was associated with improved GPT completion times, underscoring its potential in facilitating motor learning. CONCLUSIONS The study underscores that while EA and MT individually augment motor cortex excitability and performance, their synergistic application does not further enhance or inhibit cortical excitability. This points to the involvement of non-homeostatic metaplasticity mechanisms. Nonetheless, EA emerges as a critical tool in preventing M1 overstimulation, thereby continuously fostering motor learning. The findings call for further research into the strategic application of EA, whether in isolation or with MT, within clinical settings to optimize rehabilitation outcomes.

Elucidating the Role of circTIAM1 in Guangling Large-Tailed Sheep Adipocyte Proliferation and Differentiation via the miR-485-3p/PLCB1 Pathway.

Fat tissue-a vital energy storage organ-is intricately regulated by various factors, including circular RNA, which plays a significant role in modulating fat development and lipid metabolism. Therefore, this study aims to clarify the regulatory mechanism of sheep adipocyte proliferation and differentiation by investigating the involvement of circTIAM1, miR-485-3p, and its target gene PLCB1. Through previous sequencing data, circTIAM1 was identified in sheep adipocytes, with its circularization mechanism elucidated, confirming its cytoplasmic localization. Experimental evidence from RNase R treatment and transcription inhibitors highlighted that circTIAM1 is more stable than linear RNA. Additionally, circTIAM1 promoted sheep adipocyte proliferation and differentiation. Furthermore, bioinformatic analysis demonstrated a robust interaction between miR-485-3p and circTIAM1. Further experiments revealed that miR-485-3p inhibits fat cell proliferation and differentiation by inhibiting PLCB1, with circTIAM1 alleviating the inhibitory effect via competitive binding. In summary, our findings elucidate the mechanism through which circTIAM1 regulates Guangling Large-Tailed sheep adipocyte proliferation and differentiation via the miR-485-3p-PLCB1 pathway, offering a novel perspective for further exploring fat metabolism regulation.

Preparation, structural and morphological characterization of cartilage type II collagen peptide assemblies from sturgeon head.

BACKGROUND: Sturgeon cartilage type II collagen peptides (SHCPs) can self-assemble and be used to prepare collagen peptide assemblies. Self-assembled peptides have great potential for applications in the food industry. In the present study, self-assembled peptides were prepared from sturgeon cartilage and then characterized. RESULTS: The SHCPs self-assembled and formed collagen peptide assemblies. After response surface experiment optimization, the optimal enzyme digestion process comprised 43.1 °C, 3.37 h and 0.96% enzyme addition, and the peptide yield was 78.46%. Physicochemical analysis showed that the SHCPs were amphiphilic, with an average molecular weight of 1081 Da, and were rich in hydrophobic amino acids. Peptide sequence identification showed that the peptides of SHCPs with polar amino acids followed by hydrophobic amino acids could be self-assembled through hydrogen bonding and hydrophobic interaction. Through turbidity experiments, Fourier transform infrared spectroscopy and scanning electron microscopy, we demonstrated that SHCPs can self-assemble into reticular and tubular structures under specific conditions. Furthermore, both the SHCPs-Ca and SHCPs-Mg assemblies were stabilized within a pH range consistent with that of the human gastrointestinal tract. CONCLUSION: The present study provides a simple and safe method for preparing novel self-assembled peptide materials from sturgeon by-products, providing a scientific basis for the exploitation of sturgeon cartilage and potentially reducing resource wastage. © 2024 Society of Chemical Industry.

Spatiotemporal patterns of surface ozone exposure inequality in China.

Rising surface ozone (O3) levels in China are increasingly emphasizing the potential threats to public health, ecological balance, and economic sustainability. Using a 1 km × 1 km dataset of O3 concentrations, this research employs subpopulation demographic data combined with a population-weighted quality model. Its aim is to evaluate quantitatively the differences in O3 exposure among various subpopulations within China, both at a provincial and urban cluster level. Additionally, an exposure disparity indicator was devised to establish unambiguous exposure risks among significant urban agglomerations at varying O3 concentration levels. The findings reveal that as of 2018, the population-weighted average concentration of O3 for all subgroups has experienced a significant uptick, surpassing the average O3 concentration (118 µg/m3). Notably, the middle-aged demographic exhibited the highest O3 exposure level at 135.7 µg/m3, which is significantly elevated compared to other age brackets. Concurrently, there exists a prominent positive correlation between educational attainment and O3 exposure levels, with the medium-income bracket showing the greatest susceptibility to O3 exposure risks. From an industrial vantage point, the secondary sector demographic is the most adversely impacted by O3 exposure. In terms of urban-rural structure, urban groups in all regions had higher levels of exposure to O3 than rural areas, with North and East China having the most significant levels of exposure. These findings not only emphasize the intricate interplay between public health and environmental justice but further highlight the indispensability of segmented subgroup strategies in environmental health risk assessment. Moreover, this research furnishes invaluable scientific groundwork for crafting targeted public health interventions and sustainable air quality management policies.

Progress in understanding primary glomerular disease: insights from urinary proteomics and in-depth analyses of potential biomarkers based on bioinformatics.

Chronic kidney disease (CKD) has become a global public health challenge. While primary glomerular disease (PGD) is one of the leading causes of CKD, the specific pathogenesis of PGD is still unclear. Accurate diagnosis relies largely on invasive renal biopsy, which carries risks of bleeding, pain, infection and kidney vein thrombosis. Problems with the biopsy procedure include lack of glomeruli in the tissue obtained, and the sampling site not being reflective of the overall lesion in the kidney. Repeated renal biopsies to monitor disease progression cannot be performed because of the significant risks of bleeding and kidney vein thrombosis. On the other hand, urine collection, a noninvasive method, can be performed repeatedly, and urinary proteins can reflect pathological changes in the urinary system. Advancements in proteomics technologies, especially mass spectrometry, have facilitated the identification of candidate biomarkers in different pathological types of PGD. Such biomarkers not only provide insights into the pathogenesis of PGD but also are important for diagnosis, monitoring treatment, and prognosis. In this review, we summarize the findings from studies that have used urinary proteomics, among other omics screens, to identify potential biomarkers for different types of PGD. Moreover, we performed an in-depth bioinformatic analysis to gain a deeper understanding of the biological processes and protein-protein interaction networks in which these candidate biomarkers may participate. This review, including a description of an integrated analysis method, is intended to provide insights into the pathogenesis, noninvasive diagnosis, and personalized treatment efforts of PGD and other associated diseases.

Current status and challenges in establishing reference intervals based on real-world data.

Reference intervals (RIs) are the cornerstone for evaluation of test results in clinical practice and are invaluable in judging patient health and making clinical decisions. Establishing RIs based on clinical laboratory data is a branch of real-world data mining research. Compared to the traditional direct method, this indirect approach is highly practical, widely applicable, and low-cost. Improving the accuracy of RIs requires not only the collection of sufficient data and the use of correct statistical methods, but also proper stratification of heterogeneous subpopulations. This includes the establishment of age-specific RIs and taking into account other characteristics of reference individuals. Although there are many studies on establishing RIs by indirect methods, it is still very difficult for laboratories to select appropriate statistical methods due to the lack of formal guidelines. This review describes the application of real-world data and an approach for establishing indirect reference intervals (iRIs). We summarize the processes for establishing iRIs using real-world data and analyze the principle and applicable scope of the indirect method model in detail. Moreover, we compare different methods for constructing growth curves to establish age-specific RIs, in hopes of providing laboratories with a reference for establishing specific iRIs and giving new insight into clinical laboratory RI research. (201 words).

Distinct invasive patterns in situ between estrogen receptor-positive and triple-negative breast cancer through the intraductal tracking of carbon nanoparticles.

Given that the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer (BC) is crucial during the BC progression, the mechanism involved in the invasion transition behind triple-negative breast cancer (TNBC) and estrogen receptor-positive (ER-positive) subtype has remained elusive. This article detected distinct invasion patterns of BC cells between the ER-positive and TNBC using intraductal murine models with intraductal administration of carbon nanoparticles (CNPs). First, the feasibility of the utility of CNPs as a tracer was proved. The area ratio of CNPs and tumor cells invading the stroma at the late stage was found significantly higher than that in the early stage in MNU-induced ER-positive BC. However, opposite results were obtained in the triple-negative model. Consequently, we proposed that the ER-positive phenotype cells behave differently between different stages during tumor progression while there is no such difference in the invasion process of TNBC cells. The analysis regarding the duct integrity along with immunohistochemical characteristics further explained the distinct invasion features between the ER-positive and triple-negative subtypes. Last, the relationship between the duct thickness and the duct integrity suggested that ER-positive tumors gradually increased in size within the lumen before the invasion. Overall, this study suggested the different invasion characteristics of ER-positive BC and TNBC in vivo.

PLEK2 and IFI6, representing mesenchymal and immune-suppressive microenvironment, predicts resistance to neoadjuvant immunotherapy in esophageal squamous cell carcinoma.

BACKGROUND: Immunotherapy has largely improved clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). However, a proportion of patients still fail to benefit. Thus, biomarkers predicting therapeutic resistance and underlying mechanism needs to be investigated. METHODS: Transcriptomic profiling was applied in FFPE tissues from 103 ESCC patients, including surgical samples from 66 treatment-naïve patients with long-term follow-up, and endoscopic biopsies from 37 local advanced ESCC cases receiving neoadjuvant immunotherapy plus chemotherapy. Unsupervised clustering indicated an aggressive phenotype with mesenchymal character in 66 treatment-naïve samples. Univariant logistic regression was applied to identify candidate biomarkers potentially predicted resistance to neoadjuvant immunotherapy within the range of mesenchymal phenotype enriched genes. These biomarkers were further validated by immunohistochemistry. Putative mechanisms mediating immunotherapy resistance, as indicated by microenvironment and immune cell infiltration, were evaluated by transcriptomic data, and validated by multiplex immunofluorescence. RESULTS: PLEK2 and IFI6, highly expressed in mesenchymal phenotype, were identified as novel biomarkers relating to non-MPR in neoadjuvant immunotherapy cohort [PLEK2high, OR (95% CI): 2.15 (1.07-4.33), P = 0.032; IFI6high, OR (95% CI): 2.21 (1.16-4.23), P = 0.016). PLEK2high and IFI6 high ESCC patients (versus low expressed patients) further exhibit higher chance of non-major pathological remissions (90%, P = 0.004) in neoadjuvant immunotherapy cohort and high mortality (78.9%, P = 0.05), poor prognosis in retrospective cohort. PLEK2high/IFI6high ESCC recapitulated mesenchymal phenotype, characterized by extracellular matrix composition and matrix remodeling. In addition, PLEK2high or IFI6high ESCC displayed an immune-unfavored microenvironment, represented by positive correlating with regulatory T cells, Helper 2 T cell as well as less infiltration of B cells, effector T cells and mast cells. CONCLUSIONS: PLEK2 and IFI6 was discovered of first time to identify a distinct ESCC subpopulation cannot be benefited from neoadjuvant immunotherapy and present a poor survival, which putatively associated with mesenchymal and immune-suppressive microenvironment.

H2 O2 -Induced Persistent Luminescence Signal Enhancement Applied to Biosensing.

Persistent luminescence nanoparticles (PLNPs) are innovative materials able to emit light for a long time after the end of their excitation. Thanks to this property, their detection can be separated in time from the excitation, making it possible to obtain images with a high signal-to-noise ratio. This optical property can be of particular interest for the development of in vitro biosensors. Here, we report the unexpected effect of hydrogen peroxide (H2 O2 ) on the signal intensity of ZnGa2 O4 :Cr3+ (ZGO) nanoparticles. In the presence of H2 O2 , the signal intensity of ZGO can be amplified. This signal amplification can be used to detect and quantify H2 O2 in various media, using non-functionalized ZGO nanoparticles. This small molecule can be produced by several oxidases when they react with their substrate. Indeed, the quantification of glucose, lactic acid, and uric acid is possible. The limit of detection could be lowered by modifying the nanoparticles synthesis route. These optimized nanoparticles can also be used as new biosensor to detect larger molecules such as antigen, using the appropriate antibody. This unique property, i.e., persistent luminescence signal enhancement induced by H2 O2 , represents a new way to detect biomolecules which could lead to a very large number of bioassay applications.

Underwater Biomimetic Lateral Line Sensor Based on Triboelectric Nanogenerator for Dynamic Pressure Monitoring and Trajectory Perception.

Developing desirable sensors is crucial for underwater perceptions and operations. The perceiving organs of marine creatures have greatly evolved to react accurately and promptly underwater. Inspired by the fish lateral line, this study proposes a triboelectric dynamic pressure sensor for underwater perception. The biomimetic lateral line sensor (BLLS) has high sensitivity to the disturbance amplitude/frequency, good adaptability to underwater environments and (relative) low cost. The sensors are deployed at the bottom of the test basin to perceive various moving objects, such as a robotic fish, robotic seal, etc. By analyzing the electrical signal of the sensor, the motion parameters of the objects passed over can be obtained. By monitoring signal variations across multiple sensors, the ability to sense different disturbance movement trajectories, including linear and angular trajectories, is achievable. The study will prove significant in forming an unconventional underwater perceiving method, which can back-up the sonic/optical sensors when are impaired in complex underwater environments.