Density Clustering Algorithm Based on KD-Tree and Voting Rules

Traditional clustering algorithms often struggle to produce satisfactory results when dealing with datasets withuneven density. Additionally, they incur substantial computational costs when applied to high-dimensional datadue to calculating similarity matrices. To alleviate these issues, we employ the KD-Tree to partition the dataset andcompute the K-nearest neighbors (KNN) density for each point, thereby avoiding the computation of similaritymatrices. Moreover, we apply the rules of voting elections, treating each data point as a voter and casting a votefor the point with the highest density among its KNN. By utilizing the vote counts of each point, we develop thestrategy for classifying noise points and potential cluster centers, allowing the algorithm to identify clusters withuneven density and complex shapes. Additionally, we define the concept of “adhesive points” between two clustersto merge adjacent clusters that have similar densities. This process helps us identify the optimal number of clustersautomatically. Experimental results indicate that our algorithm not only improves the efficiency of clustering butalso increases its accuracy.

Fuzzy cluster analysis of water mass in the western Taiwan Strait in spring 2019

The classification of the springtime water mass has an important influence on the hydrography,regional climate change and fishery in the Taiwan Strait.Based on 58 stations of CTD profiling data collected in the western and southwestern Taiwan Strait during the spring cruise of 2019,we analyze the spatial distributions of temperature(T)and salinity(S)in the investigation area.Then by using the fuzzy cluster method combined with the T-S similarity number,we classify the investigation area into 5 water masses:the Minzhe Coastal Water(MZCW),the Taiwan Strait Mixed Water(TSMW),the South China Sea Surface Water(SCSSW),the South China Sea Subsurface Water(SCSUW)and the Kuroshio Branch Water(KBW).The MZCW appears in the near surface layer along the western coast of Taiwan Strait,showing low-salinity(<32.0)tongues near the Minjiang River Estuary and the Xiamen Bay mouth.The TSMW covers most upper layer of the investigation area.The SCSSW is mainly distributed in the upper layer of the southwestern Taiwan Strait,beneath which is the SCSUW.The KBW is a high temperature(core value of 26.36℃)and high salinity(core value of 34.62)water mass located southeast of the Taiwan Bank and partially in the central Taiwan Strait.

Combined peripheral natural killer cell and circulating tumor cell enumeration enhance prognostic efficiency in patients with metastatic triple-negative breast cancer

Objective：Triple-negative breast cancer（TNBC）is a heterogeneous disease with poor prognosis.Circulating tumor cells（CTCs）are a promising predictor for breast cancer prognoses but their reliability regarding progression-free survival（PFS）is controversial.We aim to verify their predictive value in TNBC.Methods：In present prospective cohort study,we used the Pep@MNPs method to enumerate CTCs in baseline blood samples from 75 patients with TNBC（taken at inclusion in this study）and analyzed correlations between CTC numbers and outcomes and other clinical parameters.Results：Median PFS was 6.0（range：1.0–25.0）months for the entire cohort,in whom we found no correlations between baseline CTC status and initial tumor stage（P=0.167）,tumor grade（P=0.783）or histological type（P=0.084）.However,among those getting first-line treatment,baseline CTC status was positively correlated with ratio of peripheral natural killer（NK）cells（P=0.032）,presence of lung metastasis（P=0.034）and number of visceral metastatic site（P=0.037）.Baseline CTC status was predictive for PFS in first-line TNBC（P=0.033）,but not for the cohort as a whole（P=0.118）.This prognostic limitation of CTC could be ameliorated by combining CTC and NK cell enumeration（P=0.049）.Conclusions：Baseline CTC status was predictive of lung metastasis,peripheral NK cell ratio and PFS in TNBC patients undergoing first-line treatment.We have developed a combined CTC-NK enumeration strategy that allows us to predict PFS in TNBC without any preconditions.

Identifying EGFR-Expressed Cells and Detecting EGFR Multi-Mutations at Single-Cell Level by Microfluidic Chip

EGFR mutations companion diagnostics have been proved to be crucial for the efficacy of tyrosine kinase inhibitor targeted cancer therapies. To uncover multiple mutations occurred in minority of EGFR-mutated cells,which may be covered by the noises from majority of unmutated cells, is currently becoming an urgent clinical requirement. Here we present the validation of a microfluidic-chip-based method for detecting EGFR multimutations at single-cell level. By trapping and immunofluorescently imaging single cells in specifically designed silicon microwells, the EGFR-expressed cellswere easily identified. By in situ lysing single cells, the cell lysates of EGFR-expressed cells were retrieved without cross-contamination. Benefited from excluding the noise from cells without EGFR expression, the simple and cost-effective Sanger's sequencing, but not the expensive deep sequencing of the whole cell population, was used to discover multi-mutations. We verified the new method with precisely discovering three most important EGFR drugrelated mutations from a sample in which EGFR-mutated cells only account for a small percentage of whole cell population. The microfluidic chip is capable of discovering not only the existence of specific EGFR multi-mutations,but also other valuable single-cell-level information: on which specific cells the mutations occurred, or whether different mutations coexist on the same cells. This microfluidic chip constitutes a promising method to promote simple and cost-effective Sanger's sequencing to be a routine test before performing targeted cancer therapy.

Selective catalytic reduction failure of low NH_(3)-NO_(x) ratio

An insufficient amount of NH_(3) (ammonia)will reduce the conversion efficiency of NO_(x),which may lead to excess NO_(x) emissions,resulting in NH3SCR failure.In this article,SCR failure caused by a low NH_(3)NO_(x) ratio is studied systematically by experiments.The main reasons for a low NH_(3)NO_(x) ratio in SCR include insufficient urea injection,hydrothermal aging of catalysts and urea crystallization.It was found from an insufficient urea injection experiment that with the increase of NH_(3)NO_(x) ratio,the NO_(x) conversion efficiency of the SCR system increased,but the ammonia leakage also increased.The main influencing factors of NO_(x) conversion efficiency are different under different NH3NOx ratios.A flow reactor system was used in the catalyst hydrothermal aging experiment to investigate the effect of hydrothermal aging on catalyst activity.After a 24 h hydrothermal aging experiment at 800℃,the NO_(x) conversion efficiency of the copperbased zeolite catalysts decreased significantly at the boundary of medium and low temperature regions.And the NO_(2)-NO_(x) ratio in the mixture had a significant effect on the catalytic performance.Thermogravimetry coupled to Fourier transform infrared spectroscopy(TGFTIR)was used to analyze the composition of urea deposits in a urea deposits analysis experiment.It was found that the main components of urea deposits were urea and isocyanic acid(HNCO).Preventing HNCO polymerization,especially the formation of CYA,can decrease the formation of urea deposits.

Effect of catalyst diesel particulate filter aging and catalyst loadings on particulate emission characteristics from a diesel vehicle

In this study,the effect of new and used catalyzed diesel particulate filter(CDPF)with different catalyst loadings on the particulate emissions including the particle mass(PM),particle number(PN),particle size distribution(PSD)and geometric mean diameter(GMD)from a diesel vehicle were investigated based on a heavy chassis dynamometer.Results showed that more than 97.9%of the PN and 95.4%of the PM were reduced by the CDPF,and the reduction efficiency was enhanced by the catalyst loading.After using the CDPF,the PSD transformed from bimodal to trimodal with the peak shifting towards smaller particle size,more nucleation mode particles were reduced compared with accumulation mode ones,but the reduction effect on the accumulation mode particles was more significantly influenced by the catalyst loading.Notably,the CDPF increased the accumulation mode particles proportion,producing a larger GMD.For the used CDPF,its reduction effect on the particulate emissions enhanced,especially for the PM in accumulation mode.The PSD returned to bimodal,but the peak at accumulation mode began to be higher than that at nucleation mode,illustrating that more nucleation mode particles was removed.The aging of the CDPF resulted in greater effect on the PN-based PSD than that of PM-based PSD,but the effect of catalyst loading on the PN and PM emission factors was weakened.The used CDPF further increased the GMD,and the effect of catalyst loading on the GMD was strengthened,a higher catalyst loading led to a reduction in the GMD.

A humidity resistant and high performance triboelectric nanogenerator enabled by vortex-induced vibration for scavenging wind energy

Wind energy is a promising renewable energy source for a low-carbon society.This study is to develop a fully packaged vortexinduced vibration triboelectric nanogenerator(VIV-TENG)for scavenging wind energy.The VIV-TENG consists of a wind vane,internal power generation unit,an external frame,four springs,a square cylinder and a circular turntable.The internal power generation unit consists of polytetrafluoroethylene(PTFE)balls,a honeycomb frame and two copper electrodes.Different from most of the previous wind energy harvesting TENGs,the bouncing PTFE balls are fully packaged in the square cylinder.The distinct design separates the process of contact electrification from the external environment,and at the same time avoids the frictional wear of the ordinary wind energy harvesting TENGs.The corresponding VIV parameters are investigated to evaluate their influence on the vibration behaviors and the energy output.Resonant state of the VIV-TENG corresponds to the high output performance from the VIV-TENG.The distinct,robust structure ensures the full-packaged VIV-TENG can harvest wind energy from arbitrary directions and even in undesirable weather conditions.The study proposes a novel TENG configuration for harvesting wind energy and the VIV-TENG proves promising powering micro-electro-mechanical appliances.

Effect of catalyzed diesel particulate filter and its catalyst loading on emission characteristics of a non-road diesel engine

In this study, the effects of a diesel oxidation catalyst(DOC) coupled with a catalyzed diesel particulate filter(CDPF) with different catalyst loadings on the power, fuel consumption,gaseous and particulate emissions from a non-road diesel engine were investigated. Results showed that the after-treatment had a negligible effect on the power and fuel consumption.The reduction effect of the DOC on the CO and hydrocarbon(HC) increased with the engine load. Further reductions occurred coupling with the CDPF. Increasing the catalyst loading resulted in a more significant reduction in the HC emissions than CO emissions. The DOC could increase the NO_(2)proportion to 37.9%, and more NO_(2)was produced when coupled with the CDPF below 250℃;above 250℃, more NO_(2)was consumed. The after-treatment could reduce more than 99% of the particle number(PN) and 98% of the particle mass(PM).Further reductions in the PN and PM occurred with a higher CDPF catalyst loading. The DOC had a better reduction effect on the nucleation particles than the accumulation ones, but the trend reversed with the CDPF. The DOC shifted the particle size distribution(PSD) to larger particles with an accumulation particle proportion increasing from 13% to 20%, and the geometric mean diameter(GMD) increased from 18.2 to 26.0 nm. The trend reversed with the CDPF and the accumulation particle proportion declined to less than 10%. A lower catalyst loading on the CDPF led to a higher proportion of nucleation particles and a smaller GMD.

Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety

Glioblastoma(GBM)has been regarded as one of the most deadly and challenging cancers to treat with extremely poor prognosis.The limited efficacy of current chemotherapies might be attributed to the presence of glioma stem cells(GSCs)as well as the difficulties in passing through the blood–brain barrier(BBB)and targeting tumor cells.Tumor-derived exosomes are emerging as novel and promising drug delivery systems.However,great concerns regarding the biosafety and BBB penetrability remain to be addressed.Herein,we have developed a simple and feasible strategy to engineer GBM cell-derived exosomes with improved biosafety termed“Exo@TDPs”to deliver the cargos of chemotherapeutic agents temozolomide(TMZ)and doxorubicin(DOX)into GBM tissues.Exo@TDPs decorated with angiopep-2(Ang-2)and CD133-targeted peptides improve the capacity to penetrate the BBB and target tumor cells.Both in vitro and in vivo studies demonstrate that Exo@TDPs can cross the BBB,target GBM cells,penetrate into deep tumor parenchyma,and release the therapeutic cargos effectively.Synergistic delivery of TMZ and DOX by Exo@TDPs exerts therapeutic effects to suppress the tumor growth and prolong the survival time of orthotopic syngeneic mouse GBM models.These findings suggest that our developed Exo@TDPs loaded with chemotherapeutic drugs may bring new possibilities for the application of tumor cell-derived exosomes for brain tumor treatment.

腹腔镜胃癌根治术中患者体温变化与压力性损伤及受压部位微环境的相关性分析

目的 分析腹腔镜下胃癌根治患者术中体温变化与压力性损伤及受压部位微环境的相关性。方法 回顾分析2019年9月至2022年9月火箭军特色医学中心收治的95例行腹腔镜下胃癌根治术的患者,按照其术后压力性损伤发生情况,分别纳入发生组、未发生组。对比2组患者手术开始时,以及手术开始后30 min、1 h、1.5 h、2 h体温和受压部位微环境变化,微环境包括肩部、臀部、足跟温度及湿度。使用Pearson相关性分析,计算体温与微环境的关系,并运用Logistic多因素回归分析,总结低温、微环境变化对压力性损伤发生的影响。结果 95例患者中,共有17例术后发生压力性损伤,发生率为17.89%,其中压力性损伤Ⅰ期12例、Ⅱ期4例、Ⅲ期1例。发生组手术开始后1.5 h、2 h体温,肩部、臀部、足跟温度、湿度较手术开始时上升,且高于未发生组同期水平,差异有统计学意义(P <0.05)。Pearson相关性分析示,患者术中体温与肩部、臀部、足跟温度及湿度均呈正相关(P<0.05)。Logistic多因素回归分析示,合并糖尿病、术中低血压、术中最高体温≥37.4℃、受压部位温度变化≥0.5℃、受压部位湿度变化≥1%均为影响腹腔镜胃癌根治术患者压力性损伤的独立危险因素(P<0.05)。结论 腹腔镜胃癌根治术患者术后发生压力性损伤患者术中体温较高、受压部位微环境变化更为明显,体温上升、受压部位微环境变化与压力性损伤发生风险上升有关。

Ultrafine particle emission characteristics of diesel engine by on-board and test bench measurement

This study investigated the emission characteristics of ultra.fine particles based on test bench and on-board measurements. The bench test results showed the ultrafine particle number concentration of the diesel engine to be in the range of （0.56-8.35）×10^8 cm^-3. The on-board measurement results illustrated that the ultra_fine particles were strongly correlated with changes in real-world driving cycles. The particle number concentration was down to 2.0 ×10^6 cm^-3 and 2.7 ×10^7 cm^-3 under decelerating and idling operations and as high as 5.0×10^8 cm^-3 under accelerating operation. It was also indicated that the particle number measured by the two methods increased with the growth of engine load at each engine speed in both cases. The particle number presented a ＂U＂ shaped distribution with changing speed at high engine load conditions, which implies that the particle number will reach its lowest level at medium engine speeds. The particle sizes of both measurements showed single mode distributions. The peak of particle size was located at about 50-80 nm in the accumulation mode particle range. Nucleation mode particles will significantly increase at low engine load operations like idling and decelerating caused by the high concentration of unburned organic compounds.

Emission reduction characteristics of a catalyzed continuously regenerating trap after-treatment system and its durability performance

The primary purpose of this study was to investigate the effect of a catalyzed continuously regenerating trap(CCRT)system composed of a diesel oxidation catalyst(DOC)and a catalyzed diesel particulate filter(CDPF)on the main gaseous and particulate emissions from an urban diesel bus,as well as the durability performance of the CCRT system.Experiments were conducted based on a heavy chassis dynamometer,and a laboratory activity test as well as X-ray photoelectron spectroscopy(XPS)test were applied to evaluate the changes of the aged CCRT catalyst.Results showed that the CCRT could reduce the CO by 71.5%and the total hydrocarbons(THC)by 88.9%,and meanwhile promote the oxidation of NO.However,the conversion rates for CO and THC dropped to 25.1%and 55.1%,respectively,after the CCRT was used for one year(~60,000 km),and the NO oxidation was also weakened.For particulate emissions,the CCRT could reduce 97.4%of the particle mass(PM)and almost 100%of the particle number(PN).The aging of the CCRT resulted in a reduced PM trapping efficiency but had no observable effect on the PN;however,it increased the proportion of nucleation mode particles.The activity test results indicated that the deterioration of the CCRT was directly relevant to the increase in the light-off temperatures of the catalyst for CO,C3H8 and NO2.In addition,the decreased concentrations of the active components Pt2+ and Pt4+ in the catalyst are also important factors in the CCRT deterioration.

A novel PD-L1 targeting peptide self-assembled nanofibers for sensitive tumor imaging and photothermal immunotherapy in vivo

Programmed death 1(PD-1)and its ligand PD-L1 are two typical immune checkpoints.Antibody-based immune checkpoint blockade(ICB)strategy targeting PD-1/PD-L1 achieved a significant therapeutic effect on cancer.However,due to the impenetrability of antibody drugs and the occurrence of immune-related adverse events,only a minority of patients benefit from this treatment.Peptides multimerization has been widely proved to be an effective method to improve receptor binding affinity through a multivalent synergistic effect.In this study,we report a novel peptide-aggregation-induced emission(AIE)hybrid supramolecular TAP,which can self-assemble into nanofibers through non-covalent interactions such as hydrogen bonds,with a specific nanomolar affinity to PD-L1 in vivo and in vitro.Combined with near-infrared agents,it can be used for tumor imaging and photothermal therapy,which enables photothermal ablation of cancer cells for generating tumor-associated antigen(TAA)and triggering a series of immunological events.Collectively,our work suggests that synthetic self-assembled peptide nanofibers can be developed as attractive platforms for active photothermal immunotherapies against cancer.

Substrate availability regulates the suppressive effects of Canada goldenrod invasion on soil respiration

Invasive alien plants not only decrease riparian vegetation diversity but also alter wetland ecosystem carbon processes,especially when they displace the original vegetation.Invasive Canada goldenrod(Solidago canadensis L.)has colonized large areas of disturbed and undisturbed land in southeastern China,yet little is known regarding how it affects soil carbon cycling.To explore the response patterns of soil respiration following S.canadensis invasion and their driving mechanisms,an observational field study and a greenhouse experiment simulating invasion were performed.In the field study,soil respiration was measured weekly from 21th July 2018 to 15th December 2018.In the greenhouse experiment,soil,autotrophic and heterotrophic respiration were measured every 1st and 15th of the month from 15th July 2019 to 15th December 2019.Soil,autotrophic and heterotrophic respiration were measured using a closed-chamber system with the deep gauze collar root exclusion method.Solidago canadensis invasion appeared to decrease the total soil CO_(2) emissions in both the field study and the greenhouse experiment.The suppressive effects on soil respiration may be attributed to S.canadensis invasion-induced alterations in the quality and quantity of available soil substrate,suggesting that S.canadensis invasion may impact soil carbon cycling via plant-released substrates and by competing for the soil available substrate with native plant and/or soil microbes.These results have substantial implications for estimations of the effects of invasive plants on belowground carbon dynamics and their contribution to the warming world.

Improvement of an Extreme Heavy Rainfall Simulation Using Nudging Assimilation

From 21 to 22 July 2012, Beijing and its surrounding areas suffered from an extreme precipitation event that was unprecedented relative to the past 61 years, and the event caused 79 deaths and reported direct economic losses of11.64 billion Yuan. However, current models have difficulty to simulate the spatial and temporal distribution characteristics of such events. Therefore, improved simulations of these extreme precipitation processes are needed. In this study, nudging methods, including grid nudging(GN) and spectral nudging(SN), and more accurate surface type data retrieved from remote sensing were used in the Weather Research and Forecasting(WRF) model to simulate this extreme precipitation case. When the default city underlay surface of the WRF model was replaced by a more accurate urban surface(NU), the precipitation intensity could be better simulated, but the peak moment of precipitation seriously lagged. Although the peak precipitation intensity simulated by the GN experiment was weak, the simulated precipitation time was basically consistent with the observations. Using GN in only the outside domain could better simulate precipitation peaks, while using GN in both the inside and outside domains could better simulate the spatial distribution characteristics of precipitation. Additionally, the precipitation from GN could be better simulated than that from SN. Overall, the two nudging methods could contribute to better simulations of this case because the nudging methods could improve the simulations of 500-hPa geopotential height, 850-hPa water vapor transport, and low-level weather systems, which are the key factors in adjusting the spatial and temporal distributions of precipitation. This study is the basis for the investigation of the mechanism and attribution of extreme precipitation processes,and the results are of great significance for promoting understanding of and mitigating disasters caused by extreme precipitation.

A novel peptide-based probe^(99m)Tc-PEG_(6)-RD-PDP2 for the molecular imaging of tumor PD-L2 expression

Tumor-related PD-L2 expression is associated with the clinical efficacy of PD-1/PD-L1 blockade therapy.PD-L2-specific imaging can help selecting patients for appropriate immunotherapy.In this study,a PD-L2-targeting peptide(PDP2)was screened by the one-bead one-compound combinatorial library approach.Using the retro-inverso D-peptide of PDP2(RD-PDP2)and PEGylation strategies,we developed a novel Tc-99m-labeled PD-L2-targeting peptide as a SPECT tracer(^(99m)Tc-PEG_(6)-RD-PDP2)for imaging of tumor PD-L2 expression.The radiolabeling yield of ^(99m)Tc-PEG_(6)-RD-PDP2 was greater than 95%by the standard HYNIC/tricine/TPPTS labeling procedure.^(99m)Tc-PEG_(6)-RD-PDP2 displayed high PD-L2-binding specificity both in vitro and in vivo.SPECT/CT imaging with^(99m)Tc-PEG_(6)-RD-PDP2 showed that the A549-PD-L2tumors were clearly visualized,whereas the signals in PD-L2-negative A549 tumors were much lower.In vivo blocking study suggested that the tumor uptake of^(99m)Tc-PEG_(6)-RD-PDP2 was PD-L2 specifically mediated.^(99m)Tc-PEG_(6)-RD-PDP2 is a promising SPECT probe for the non-invasive imaging of tumor PD-L2expression and has a great potential in guiding the anti-PD-1 or anti-PD-L1 immunotherapy of cancer.

Proteomics profiling of colorectal cancer progression identifies PLOD2 as a potential therapeutic target

Dear editors,Colorectal cancer(CRC)is the second leading cause of cancer deaths in developed countries[1].The malignant transformation from small clumps to cancer takes about 10 years[2].This study aimed to characterize proteomic dynamics associated with CRC development and progres-sion,and identify novel therapeutic targets for intercepting the underlying oncogenic processes.We have optimized pressure cycling technology(PCT)coupled with data-independent acquisition mass spectrometry(DIA-MS)for robust and reproducible proteomic analysis of biopsy-level formalin-fixed paraffin-embedded(FFPE)tissues[3].