BACKGROUND Neoadjuvant therapy(NAT)for pancreatic cancer(PC)is becoming standardized,with neoadjuvant chemoradiotherapy(NACRT)showing proven effectiveness.However,the optimal endoscopic biliary drainage approach durin...BACKGROUND Neoadjuvant therapy(NAT)for pancreatic cancer(PC)is becoming standardized,with neoadjuvant chemoradiotherapy(NACRT)showing proven effectiveness.However,the optimal endoscopic biliary drainage approach during NAT remains controversial.In this single-center retrospective case series,we report the use of a novel multi-hole self-expandable metallic stent(MH-SEMS)for preoperative biliary drainage during NACRT in patients with PC.AIM To assess the feasibility of endoscopic biliary drainage using MH-SEMS during NACRT in patients with malignant distal biliary obstruction secondary to resectable and borderline resectable PC.METHODS We included 14 patients—10 with resectable,2 with borderline resectable,and 2 with unresectable locally advanced disease—who had undergone surgery after biliary drainage using MH-SEMS(diameter:10 mm).Clinical and technical success was achieved in all patients,with a median interval of 105 days between stent placement and surgery.RESULTS A partial response was observed in five patients(35.7%),whereas nine patients(64.3%)exhibited stable disease.Only one patient(7.1%)developed moderate cholangitis from recurrent biliary obstruction caused by sludge 337 days after stent placement during systemic chemotherapy,requiring MH-SEMS replacement.Pathological examination of postoperative specimens revealed tumor shrinkage in many cases,and no stent migration was observed.Adverse events included mild pancreatitis in two patients(14.3%)and moderate pancreatitis in one patient(7.1%),as defined by the Tokyo Criteria 2024.CONCLUSION No cases of cholecystitis,liver abscess,or hemorrhage were reported.No disadvantages in surgical procedures or postoperative complications related to MH-SEMS placement were observed.展开更多
The research presented in this paper aimed to analyze the evolution of fractures in strata in relation to the progress of longwall mining.To achieve this objective,an introscopic probe equipped with a highresolution c...The research presented in this paper aimed to analyze the evolution of fractures in strata in relation to the progress of longwall mining.To achieve this objective,an introscopic probe equipped with a highresolution camera was developed,along with additional equipment that enables continuous recording of the internal surfaces of drainage boreholes exceeding 100 m in depth.The probe was utilized to test two methane drainage boreholes in the Z-3b longwall,which operates within the 501/3 coal seam of the Jankowice mine in Poland.Automatic image analysis methods were applied to evaluate the recorded images,based on a newly developed classificationsystem for fractures categorized by size and number.The results were compared with an analysis of changes in the methane capture rate from the drainage boreholes,which correlated with longwall mining progress.A strong correlation was observed between the number of fractures and the lithology of the strata layers.The largest number of fractures and their evolution were recorded in the coal layers,followed by the shale layers,while the sandstone layers exhibited the least number of fractures.Based on parallel measurements of the methane capture rate from the drainage boreholes during the progress of longwall mining,the extent of the strata's fracture zone was determined to range from 6 m to 36 m.Within the fracture zone,the strata are highly fractured,which leads to an increase in methane emissions through seepage and diffusion processes.展开更多
Cell-selective fluorescent probes have emerged as essential tools for live-cell imaging,enabling the differentiation of specific cell types within complex biological systems.Unlike traditional antibody-based methods t...Cell-selective fluorescent probes have emerged as essential tools for live-cell imaging,enabling the differentiation of specific cell types within complex biological systems.Unlike traditional antibody-based methods that target extracellular proteins,small-molecule probes can access intracellular environments and exploit diverse biochemical features for selective retention or activation.This perspective categorizes the mechanisms of cell selectivity into five principal strategies:Protein-oriented,carbohydrate-oriented,lipid-oriented,gating-oriented,and metabolism-oriented live-cell distinctions.Each class capitalizes on a unique cellular trait ranging from protein expression and membrane composition to transporter activity and metabolic enzyme presence.We discuss representative examples of each mechanism,outline a decision-tree workflow for elucidating a new probe's mode of action,and highlight how understanding these mechanisms is critical for both basic biological research and therapeutic probe design.Looking ahead,the development of such mechanism-informed cell-specific probes holds promise for advancing precision cell targeting in biomedical applications.展开更多
Schizophrenia(SCZ) is a severe mental disorder with an unclear pathogenesis.Increasing evidence suggests that oxidative stress(OS) may contribute to the neuropathological processes underlying SCZ.Biothiols,key endogen...Schizophrenia(SCZ) is a severe mental disorder with an unclear pathogenesis.Increasing evidence suggests that oxidative stress(OS) may contribute to the neuropathological processes underlying SCZ.Biothiols,key endogenous antioxidants,have been proposed as potential biomarkers for the disease.However,due to the presence of the blood-brain barrier(BBB),fluorescent probes are rarely used to image biothiols in the brain of SCZ models.In this study,a series of fluorescent probes for biothiols were developed using dicyanoisophorone derivatives as fluorophores known for their excellent optical properties,and carboxylic esters as recognition units.A parallel synthesis and rapid screening strategy was employed to construct and optimize these probes.By introducing trifluoromethyl and benzothiazole groups into the fluorophore,the emission wavelength was successfully shifted into the near-infrared region.Additionally,various trifluoromethyl-substituted aromatic and nitrogen heterocyclic compounds were incorporated to optimize the carboxylic esters,thereby improving the probes' reactivity and lipophilicity.Systematic evaluation of the physicochemical characteristics,and optical performance led to the identification of DCIBT-11 as the most promising candidate.DCI-BT-11 demonstrated excellent BBB permeability and a good response to biothiols both in vitro and in vivo.Notably,DCI-BT-11 was used for the first time to visualize biothiol flux and assess the therapeutic effects of the antioxidant N-acetylcysteine(NAC) in the brains of SCZ mouse models,offering new insights into the role of OS in the pathogenesis and treatment of SCZ.展开更多
Ferroptosis has exhibited great potential in therapies and intracellular reducing agents of sulfur species(RSSs) in the thiol-dependent redox systems are crucial in ferroptosis.This makes the simultaneous detection of...Ferroptosis has exhibited great potential in therapies and intracellular reducing agents of sulfur species(RSSs) in the thiol-dependent redox systems are crucial in ferroptosis.This makes the simultaneous detection of multiple RSSs significant for evaluating ferroptosis therapy.However,the traditional techniques,including fluorescent(FL) imaging and electrospray ionization-based mass spectrometry(MS) detection,cannot achieve the discrimination of different RSSs.Herein,simultaneous MS detection of multiple RSSs,including cysteine(Cys),homocysteine(Hcy),glutathione(GSH) and hydrogen sulfide(H_(2)S),was obtained upon enhancing ionization efficiency by a fluorescent probe(NBD-O-1).Based on the interaction between NBD-O-1 and RSSs,the complex of RSSs with a fragment of NBD-O-1 can be generated,which can be easily ionized for MS detection in the negative mode.Therefore,the intracellular RSSs can be well detected upon the incubation of He La cells with the probe of NBD-O-1,exhibiting the total RSS levels by the FL imaging and further providing expression of each RSS by enhanced MS detection.Furthermore,the RSSs during ferroptosis in He La cells have been evaluated using the present strategy,demonstrating the potential for ferroptosis examinations.This work has made an unconventional application of a fluorescent probe to enhance the detection of multiple RSSs by MS,providing significant molecular information for addressing the ferroptosis mechanism.展开更多
Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused...Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.展开更多
The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensit...The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensity changes,which can compromise accuracy and repeatability.In this study,we report a novel fluorescent probe(R)-Z1 that achieves effective enantioselective recognition of chiral amino acids in water by altering emission wavelengths(>60 nm).This water-soluble probe(R)-Z1 exhibits cyan or yellow-green luminescence upon interaction with amino acid enantiomers,enabling reliable chiral detection of 14 natural amino acids.It also allows for the determination of enantiomeric excess through monitoring changes in luminescent color.Additionally,a logic operation with two inputs and three outputs was constructed based on these optical properties.Notably,amino acid enantiomers were successfully detected via dual-channel analysis at both the food and cellular levels.This study provides a new dynamic luminescence-based tool for the accurate sensing and detection of amino acid enantiomers.展开更多
To address the challenge of low survival rates and limited data collection efficiency in current virtual probe deployments,which results from anomaly detection mechanisms in location-based service(LBS)applications,thi...To address the challenge of low survival rates and limited data collection efficiency in current virtual probe deployments,which results from anomaly detection mechanisms in location-based service(LBS)applications,this paper proposes a novel virtual probe deployment method based on user behavioral feature analysis.The core idea is to circumvent LBS anomaly detection by mimicking real-user behavior patterns.First,we design an automated data extraction algorithm that recognizes graphical user interface(GUI)elements to collect spatio-temporal behavior data.Then,by analyzing the automatically collected user data,we identify normal users’spatio-temporal patterns and extract their features such as high-activity time windows and spatial clustering characteristics.Subsequently,an antidetection scheduling strategy is developed,integrating spatial clustering optimization,load-balanced allocation,and time window control to generate probe scheduling schemes.Additionally,a self-correction mechanism based on an exponential backoff strategy is implemented to rectify anomalous behaviors andmaintain system stability.Experiments in real-world environments demonstrate that the proposed method significantly outperforms baseline methods in terms of both probe ban rate and task completion rate,while maintaining high time efficiency.This study provides a more reliable and clandestine solution for geosocial data collection and lays the foundation for building more robust virtual probe systems.展开更多
Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the q...Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the quality of these medicinal materials and contributing to various health issues.Due to a lack of effective monitoring and imaging tools,the physiological effects of excessive SO_(2) residues in traditional Chinese medicine remain unclear.Therefore,developing a rapid and effective tool for detecting SO_(2) is crucial for understanding its metabolic pathways and effects in vivo.In this study,we developed a near infrared(NIR) and ratiometric fluorescent probe,NIR-RS,which exhibits high sensitivity,selectivity,and rapid response for SO_(2) detection.Notably,NIR-RS accurately quantifies SO_(2) contents in Pinelliae rhizoma(P.rhizoma) samples,with recovery rates from 98.46 % to 102.40 %,and relative standard deviations(RSDs)< 5.0 %.For bioimaging applications,NIR-RS has low cytotoxicity and good mitochondrial-targeting ability,making it suitable for imaging exogenous and endogenous SO_(2) in mitochondria.Additionally,NIR-RS was successfully applied to image SO_(2) content of P.rhizoma samples within cells,revealing that high SO_(2) residue elevated mitochondria adenosine triphosphate(ATP) content,these findings reveal that P.rhizoma with excessive SO_(2) can affect the organism's growth mechanisms through alterations in ATP pathways.In vivo,SO_(2) was found to predominantly accumulate in the liver following gavage with P.rhizoma solution,with accumulation levels increasing in proportion to SO_(2) residue concentration.High SO_(2) concentrations in P.rhizoma can cause pulmonary fibrosis and gastric mucosal damage.This work provides a valuable tool for regulating SO_(2) content in P.rhizoma and may help researcher better understand the metabolism of SO_(2) derivatives and explore their physiological roles in biological systems.展开更多
A series of computations is conducted for many multi-hole arrangements at several blowing ratios to further investigate the evolution of the film from multi-holes. The influence of multi-hole arrangement on effusion f...A series of computations is conducted for many multi-hole arrangements at several blowing ratios to further investigate the evolution of the film from multi-holes. The influence of multi-hole arrangement on effusion film cooling is analyzed and a preliminary relationship evaluating the film development from developing state to developed state is brought forward. Results show that the coolant jets from front rows of multi-holes merge rapidly and the strength of the kidney vortices due to mainstream-coolant jet interaction in the downstream region are mitigated under super-long-diamond arrangement where the streamwise hole-to-hole pitch is bigger than spanwise hole-to-hole pitch. The holes array arranged in super-long-diamond mode is not only in favor of obtaining developed film layer, but also improving averaged adiabatic film cooling effectiveness.展开更多
This study firstly defines a set of arrangement rule for perforated holes of multi-hole orifice(MO), and then presents three critical geometrical parameters including total number of performated hole, equivalent diame...This study firstly defines a set of arrangement rule for perforated holes of multi-hole orifice(MO), and then presents three critical geometrical parameters including total number of performated hole, equivalent diameter ratio and distribution density of perforated holes, which are to quantify MO structure. This paper built the throttling test apparatus for nice test MO plates, which were designed according to orthogonal theory. The experiments were conducted to investigate the effect of three critical geometerical parameters on the pressure loss coefficient of test MOs. Results show that equivalent diameter ratio is the dominant prameter affecting MO throttling characterstic.展开更多
In order to analyze the influence of the hole chamfer on the metering performances of a Multi-hole Orifice Flowmeter and optimize the related orifice structure,a multi-hole orifice flowmeter with DN80 and throttle rat...In order to analyze the influence of the hole chamfer on the metering performances of a Multi-hole Orifice Flowmeter and optimize the related orifice structure,a multi-hole orifice flowmeter with DN80 and throttle ratio of 0.45 was considered in the present study.The flow field characteristics were determined in the framework of a CFD technique.The results show that the multi-hole orifice flowmeter with filleting transition around the throttle orifice has higher accuracy in a wide range of the space of parameters,and is more suitable for accurate measurement of fluid in process control.展开更多
Conventional surface seismic exploration in areas with complex surfaces such as karst landforms has been faced with the problem of poor excitation and reception conditions.RVSP(reverse vertical seismic profile)seismic...Conventional surface seismic exploration in areas with complex surfaces such as karst landforms has been faced with the problem of poor excitation and reception conditions.RVSP(reverse vertical seismic profile)seismic exploration adopts a geometry in which the sources are downhole and receivers are on the ground which can reduce the influence of complex surfaces on seismic wave propagation(to some extent).Through numerical simulations and real data analysis,it was noted that in areas with complex surfaces and large numbers of underground karst caves,seismic waves generated in shallow boreholes are easily affected by various surface and multiple waves as well as by scattering from karst bodies.Therefore,the quality of the reflected seismic data is extremely low.Also,it is difficult to improve the signal to noise ratio(SNR)with conventional noise filtering methods.However,when the source depth is increased,the quality of the reflected waves can be improved.This is exactly what the RVSP method accomplishes.Besides,for the RVSP method,due to its particular geometry,the apparent velocities of the reflected waves and most interference waves are quite different,which can help to filter most noise to further improve the SNR of the reflected signals.In this study,a 3 D-RVSP exploration study using 8-hole joint acquisition was conducted in a typical karst landform.The results show that the 3 D-RVSP method can obtain higher quality seismic data for complex surface conditions that have large numbers of underground karst caves.Furthermore,multi-hole joint acquisition for 3 D-RVSP has higher data collection efficiency and better uniformity of underground coverage.Therefore,in this study,38 faults were accurately revealed and at high resolution based on the 3 D-RVSP imaging results.展开更多
Based on the elementary solutions and new integral equations,a new analytical-numerical method is proposed to calculate the interacting stresses of multiple circular holes in an infinite elastic plate under both remot...Based on the elementary solutions and new integral equations,a new analytical-numerical method is proposed to calculate the interacting stresses of multiple circular holes in an infinite elastic plate under both remote stresses and arbitrarily distributed stresses applied to the circular boundaries.The validity of this new analytical-numerical method is verified by the analytical solution of the bi-harmonic stress function method,the numerical solution of the finite element method,and the analytical-numerical solutions of the series expansion and Laurent series methods.Some numerical examples are presented to investigate the effects of the hole geometry parameters(radii and relative positions)and loading conditions(remote stresses and surface stresses)on the interacting tangential stresses and interacting stress concentration factors(SCFs).The results show that whether the interference effect is shielding(k<1)or amplifying(k>1)depends on the relative orientation of holes(α)and remote stresses(σ^∞x,σ^∞y).When the maximum principal stress is aligned with the connecting line of two-hole centers andσ^∞y<0.5σ^∞x,the plate containing two circular holes has greater stability than that containing one circular hole,and the smaller circular hole has greater stability than the bigger one.This new method not only has a simple formulation and high accuracy,but also has an advantage of wide applications over common analytical methods and analytical-numerical methods in calculating the interacting stresses of a multi-hole problem under both remote and arbitrary surface stresses.展开更多
A throttling experiment for the multi-hole orifice （MO） using water was conducted based on the conclusion of key parameters affecting the MO throttling performance. Testing MOs and standard orifice plates （ SO ） w...A throttling experiment for the multi-hole orifice （MO） using water was conducted based on the conclusion of key parameters affecting the MO throttling performance. Testing MOs and standard orifice plates （ SO ） were designed for the throttling experiment to compare the throttling effect using the equivalent diameter ratio （RED） and diameter ratio （RD ） as key parameters, respectively. Meanwhile, effective metrical conditions were provided for experimental accuracy. The throttling model form was determined according to the theoretical throttling model of SO. Then the unknown parameters involved were identified by experimental data. A good concordance between the modeling computation and experimental results shows a validation of the MO throtting model.展开更多
A multi-hole vertical-cavity surface-emitting laser （VCSEL） operating in stable single mode with a low threshold current was produced by introducing multi-leaf scallop holes on the top distributed Bragg-refleetor of...A multi-hole vertical-cavity surface-emitting laser （VCSEL） operating in stable single mode with a low threshold current was produced by introducing multi-leaf scallop holes on the top distributed Bragg-refleetor of an oxidation- confined 850 nm VCSEL. The single-mode output power of 2.6 mW, threshold current of 0.6 mA, full width of half maximum lasing spectrum of less than 0.1 nm, side mode suppression ratio of 28.4 dB, and far-field divergence angle of about 10% are obtained. The effects of different hole depths on the optical characteristics are simulated and analysed, including far-field divergence, spectrum and lateral cavity mode. The single-mode performance of this multi-hole device is attributed to the large radiation loss from the inter hole spacing and the scattering loss at the bottom of the holes, particularly for higher order modes.展开更多
In the process of ion-adsorption rare earth ore leaching,the migration characteristics of the wetting front in multi-hole injection holes and the influence of wetting front intersection effect on the migration distanc...In the process of ion-adsorption rare earth ore leaching,the migration characteristics of the wetting front in multi-hole injection holes and the influence of wetting front intersection effect on the migration distance of wetting fronts are still unclear.Besides,wetting front migration distance and leaching time are usually required to optimize the leaching process.In this study,wetting front migration tests of ionadsorption rare earth ores during the multi-hole fluid injection(the spacing between injection holes was 10 cm,12 cm and 14 cm)and single-hole fluid injection were completed under the constant water head height.At the pre-intersection stage,the wetting front migration laws of ion-adsorption rare earth ores during the multi-hole fluid injection and single-hole fluid injection were identical.At the postintersection stage,the intersection accelerated the wetting front migration.By using the Darcy’s law,the intersection effect of wetting fronts during the multi-hole liquid injection was transformed into the water head height directly above the intersection.Finally,based on the Green-Ampt model,a wetting front migration model of ion-adsorption rare earth ores during the multi-hole unsaturated liquid injection was established.Error analysis results showed that the proposed model can accurately simulate the infiltration process under experimental conditions.The research results enrich the infiltration law and theory of ion-adsorption rare earth ores during the multi-hole liquid injection,and this study provides a scientific basis for optimizing the liquid injection well pattern parameters of ion-adsorption rare earth in situ leaching in the future.展开更多
BACKGROUND Uncovered stents used for malignant obstructions in the biliary tree, especially in the hilar area, are prone to obstruction by tumor ingrowths. In comparison, however, covered stents may block bile duct br...BACKGROUND Uncovered stents used for malignant obstructions in the biliary tree, especially in the hilar area, are prone to obstruction by tumor ingrowths. In comparison, however, covered stents may block bile duct branches and are at risk of migration. We have developed a multi-hole self-expandable metallic stent (MHSEMS), with a hole in each cell, to prevent the obstruction of bile duct branches. In addition, the holes may prevent migration due to small ingrowths by reducing the tension of the membrane. CASE SUMMARY MHSEMS were placed in five patients with a malignant obstruction and one with post-endoscopic sphincterotomy bleeding. Each MHSEMS was successfully deployed in all cases. Patients showed no complications. Two cases were reviewed. Case 1: A 74-year-old male presented with jaundice and was diagnosed with a sigmoid colon cancer and giant liver metastases in the right liver lobe. A MHSEMS was placed in the left bile duct. The jaundice improved and peroral cholangioscopy was performed. Case 2: A 90-year-old female was admitted to hospital for jaundice and diagnosed with cholangiocarcinoma. A MHSEMS was placed in the left bile duct but after 8 months the stent became obstructed by tumor ingrowth. We treated the patient by ablation therapy. A silicone cover separated the internal bile duct from the surrounding tissue, protecting the latter from thermal injury during treatment by endobiliary ablation of the reobstruction. CONCLUSION A MHSEMS is a new choice of stent for biliary tract diseases.展开更多
Combining real accelerating genetic algorithm(RAGA) with the optimization design of multi-hole and varied diameter pipe, the authors solved the problem of optimizing multi-dimensional parameters at the same time. In w...Combining real accelerating genetic algorithm(RAGA) with the optimization design of multi-hole and varied diameter pipe, the authors solved the problem of optimizing multi-dimensional parameters at the same time. In which the advanced convergence and easily to run into partial optimization were avoid. Applied the RAGA to solving the problem in the optimization design of fixed piping sprinkler irrigation system. The optimized parameters, such as diameters and the length of pipe were calculated and the result was reasonable, which provides as a reference to readers who work at related research.展开更多
This article provides a short review on the importance of the detailed analysis of a Langmuir probe I-V trace in a multi-Maxwellian plasma,and discuss proper procedures analyzing Langmuir probe I-V traces in bi-Maxwel...This article provides a short review on the importance of the detailed analysis of a Langmuir probe I-V trace in a multi-Maxwellian plasma,and discuss proper procedures analyzing Langmuir probe I-V traces in bi-Maxwellian and triple-Maxwellian Electron Energy Distribution Function(EEDF)plasmas.Discus⁃sion and demonstration of procedures include the treatment of the ion saturation current,electron saturation cur⁃rent,space-charge effects on the I-V trace,and most importantly how to properly isolate and fit for each electron group present in an I-V trace reflecting a mult-Maxwellian EEDF,as well as how having a multi-Maxwellian EEDF affects the procedures of treating the ion and electron saturation currents.Shortcomings of common improp⁃er procedures are discussed and demonstrated with simulated I-V traces to show how these procedures gives false measurements.展开更多
文摘BACKGROUND Neoadjuvant therapy(NAT)for pancreatic cancer(PC)is becoming standardized,with neoadjuvant chemoradiotherapy(NACRT)showing proven effectiveness.However,the optimal endoscopic biliary drainage approach during NAT remains controversial.In this single-center retrospective case series,we report the use of a novel multi-hole self-expandable metallic stent(MH-SEMS)for preoperative biliary drainage during NACRT in patients with PC.AIM To assess the feasibility of endoscopic biliary drainage using MH-SEMS during NACRT in patients with malignant distal biliary obstruction secondary to resectable and borderline resectable PC.METHODS We included 14 patients—10 with resectable,2 with borderline resectable,and 2 with unresectable locally advanced disease—who had undergone surgery after biliary drainage using MH-SEMS(diameter:10 mm).Clinical and technical success was achieved in all patients,with a median interval of 105 days between stent placement and surgery.RESULTS A partial response was observed in five patients(35.7%),whereas nine patients(64.3%)exhibited stable disease.Only one patient(7.1%)developed moderate cholangitis from recurrent biliary obstruction caused by sludge 337 days after stent placement during systemic chemotherapy,requiring MH-SEMS replacement.Pathological examination of postoperative specimens revealed tumor shrinkage in many cases,and no stent migration was observed.Adverse events included mild pancreatitis in two patients(14.3%)and moderate pancreatitis in one patient(7.1%),as defined by the Tokyo Criteria 2024.CONCLUSION No cases of cholecystitis,liver abscess,or hemorrhage were reported.No disadvantages in surgical procedures or postoperative complications related to MH-SEMS placement were observed.
基金the PICTO project(RFCR-CT-2018-800711)funded by the European Research Fund for Coal and Steel(RFCS)and the Polish Ministry of Science and Higher Education(W93/FBWiS/2018).
文摘The research presented in this paper aimed to analyze the evolution of fractures in strata in relation to the progress of longwall mining.To achieve this objective,an introscopic probe equipped with a highresolution camera was developed,along with additional equipment that enables continuous recording of the internal surfaces of drainage boreholes exceeding 100 m in depth.The probe was utilized to test two methane drainage boreholes in the Z-3b longwall,which operates within the 501/3 coal seam of the Jankowice mine in Poland.Automatic image analysis methods were applied to evaluate the recorded images,based on a newly developed classificationsystem for fractures categorized by size and number.The results were compared with an analysis of changes in the methane capture rate from the drainage boreholes,which correlated with longwall mining progress.A strong correlation was observed between the number of fractures and the lithology of the strata layers.The largest number of fractures and their evolution were recorded in the coal layers,followed by the shale layers,while the sandstone layers exhibited the least number of fractures.Based on parallel measurements of the methane capture rate from the drainage boreholes during the progress of longwall mining,the extent of the strata's fracture zone was determined to range from 6 m to 36 m.Within the fracture zone,the strata are highly fractured,which leads to an increase in methane emissions through seepage and diffusion processes.
基金supported by the Starting growth Technological R&D Program(TIPS Program,RS-2024-00468327)funded by the Ministry of SMEs and Startups(MSS,Korea)in 2024 and National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(Nos.2023R1A2C300453411 and RS2024-00411069),Glocal University 30 project(Molecular Imaging Center,POSTECH).
文摘Cell-selective fluorescent probes have emerged as essential tools for live-cell imaging,enabling the differentiation of specific cell types within complex biological systems.Unlike traditional antibody-based methods that target extracellular proteins,small-molecule probes can access intracellular environments and exploit diverse biochemical features for selective retention or activation.This perspective categorizes the mechanisms of cell selectivity into five principal strategies:Protein-oriented,carbohydrate-oriented,lipid-oriented,gating-oriented,and metabolism-oriented live-cell distinctions.Each class capitalizes on a unique cellular trait ranging from protein expression and membrane composition to transporter activity and metabolic enzyme presence.We discuss representative examples of each mechanism,outline a decision-tree workflow for elucidating a new probe's mode of action,and highlight how understanding these mechanisms is critical for both basic biological research and therapeutic probe design.Looking ahead,the development of such mechanism-informed cell-specific probes holds promise for advancing precision cell targeting in biomedical applications.
基金supported by the National Natural Science Foundation of China (Nos.22177025,21807021,22177026)the Science Fund for Creative Research Groups of the Natural Science Foundation of Hebei Province (No.B2021201038)+1 种基金the Foundation of Hebei University (No.050001-513300201004)the Director’s Foundation of the Key Laboratory of Medicinal Chemistry and Molecular Diagnosis,Ministry of Education,Hebei University (No.MCMDZR2024003)。
文摘Schizophrenia(SCZ) is a severe mental disorder with an unclear pathogenesis.Increasing evidence suggests that oxidative stress(OS) may contribute to the neuropathological processes underlying SCZ.Biothiols,key endogenous antioxidants,have been proposed as potential biomarkers for the disease.However,due to the presence of the blood-brain barrier(BBB),fluorescent probes are rarely used to image biothiols in the brain of SCZ models.In this study,a series of fluorescent probes for biothiols were developed using dicyanoisophorone derivatives as fluorophores known for their excellent optical properties,and carboxylic esters as recognition units.A parallel synthesis and rapid screening strategy was employed to construct and optimize these probes.By introducing trifluoromethyl and benzothiazole groups into the fluorophore,the emission wavelength was successfully shifted into the near-infrared region.Additionally,various trifluoromethyl-substituted aromatic and nitrogen heterocyclic compounds were incorporated to optimize the carboxylic esters,thereby improving the probes' reactivity and lipophilicity.Systematic evaluation of the physicochemical characteristics,and optical performance led to the identification of DCIBT-11 as the most promising candidate.DCI-BT-11 demonstrated excellent BBB permeability and a good response to biothiols both in vitro and in vivo.Notably,DCI-BT-11 was used for the first time to visualize biothiol flux and assess the therapeutic effects of the antioxidant N-acetylcysteine(NAC) in the brains of SCZ mouse models,offering new insights into the role of OS in the pathogenesis and treatment of SCZ.
基金supported by the National Key Research and Development Program of China (No.2024YFA1509600)National Natural Science Foundation of China (Nos.22474010 and 22274012)the Fundamental Research Funds for the Central Universities (No.2233300007)。
文摘Ferroptosis has exhibited great potential in therapies and intracellular reducing agents of sulfur species(RSSs) in the thiol-dependent redox systems are crucial in ferroptosis.This makes the simultaneous detection of multiple RSSs significant for evaluating ferroptosis therapy.However,the traditional techniques,including fluorescent(FL) imaging and electrospray ionization-based mass spectrometry(MS) detection,cannot achieve the discrimination of different RSSs.Herein,simultaneous MS detection of multiple RSSs,including cysteine(Cys),homocysteine(Hcy),glutathione(GSH) and hydrogen sulfide(H_(2)S),was obtained upon enhancing ionization efficiency by a fluorescent probe(NBD-O-1).Based on the interaction between NBD-O-1 and RSSs,the complex of RSSs with a fragment of NBD-O-1 can be generated,which can be easily ionized for MS detection in the negative mode.Therefore,the intracellular RSSs can be well detected upon the incubation of He La cells with the probe of NBD-O-1,exhibiting the total RSS levels by the FL imaging and further providing expression of each RSS by enhanced MS detection.Furthermore,the RSSs during ferroptosis in He La cells have been evaluated using the present strategy,demonstrating the potential for ferroptosis examinations.This work has made an unconventional application of a fluorescent probe to enhance the detection of multiple RSSs by MS,providing significant molecular information for addressing the ferroptosis mechanism.
基金supported by the following grants:National Natural Science Foundation of China(Grant Nos.92354305 and 32271428),National Key R&D Program of China(Grant No.2022YFC3401100)Young Talent Program of Hubei Provincial Health Commission(WJ2025Q037)+1 种基金Interdisciplinary Research Program of HUST(Grant No.2023JCY5045)Director Fund of WNLO.
文摘Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.
基金the financial support from the National Natural Science Foundation of China(Nos.22377097,22307036,22074114)Natural Science Foundation of Hubei Province of China(Nos.2020CFB623,2021CFB556)Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education(No.LCX202305)。
文摘The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensity changes,which can compromise accuracy and repeatability.In this study,we report a novel fluorescent probe(R)-Z1 that achieves effective enantioselective recognition of chiral amino acids in water by altering emission wavelengths(>60 nm).This water-soluble probe(R)-Z1 exhibits cyan or yellow-green luminescence upon interaction with amino acid enantiomers,enabling reliable chiral detection of 14 natural amino acids.It also allows for the determination of enantiomeric excess through monitoring changes in luminescent color.Additionally,a logic operation with two inputs and three outputs was constructed based on these optical properties.Notably,amino acid enantiomers were successfully detected via dual-channel analysis at both the food and cellular levels.This study provides a new dynamic luminescence-based tool for the accurate sensing and detection of amino acid enantiomers.
基金supported by theNationalNatural Science Foundation of China(No.U23A20305)National Key Research and Development Program of China(No.2022YFB3102900)+1 种基金Innovation Scientists and Technicians Troop Construction Projects of Henan Province,China(No.254000510007)Key Research and Development Project of Henan Province(No.221111321200).
文摘To address the challenge of low survival rates and limited data collection efficiency in current virtual probe deployments,which results from anomaly detection mechanisms in location-based service(LBS)applications,this paper proposes a novel virtual probe deployment method based on user behavioral feature analysis.The core idea is to circumvent LBS anomaly detection by mimicking real-user behavior patterns.First,we design an automated data extraction algorithm that recognizes graphical user interface(GUI)elements to collect spatio-temporal behavior data.Then,by analyzing the automatically collected user data,we identify normal users’spatio-temporal patterns and extract their features such as high-activity time windows and spatial clustering characteristics.Subsequently,an antidetection scheduling strategy is developed,integrating spatial clustering optimization,load-balanced allocation,and time window control to generate probe scheduling schemes.Additionally,a self-correction mechanism based on an exponential backoff strategy is implemented to rectify anomalous behaviors andmaintain system stability.Experiments in real-world environments demonstrate that the proposed method significantly outperforms baseline methods in terms of both probe ban rate and task completion rate,while maintaining high time efficiency.This study provides a more reliable and clandestine solution for geosocial data collection and lays the foundation for building more robust virtual probe systems.
基金supported by the Natural Science Foundation of Hubei Province (Nos.2023AFB376 and 2024AFD287)National Key Research and Development Program (No.2023YFC3503804)the National Natural Science Foundation of China (No.22077044)。
文摘Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the quality of these medicinal materials and contributing to various health issues.Due to a lack of effective monitoring and imaging tools,the physiological effects of excessive SO_(2) residues in traditional Chinese medicine remain unclear.Therefore,developing a rapid and effective tool for detecting SO_(2) is crucial for understanding its metabolic pathways and effects in vivo.In this study,we developed a near infrared(NIR) and ratiometric fluorescent probe,NIR-RS,which exhibits high sensitivity,selectivity,and rapid response for SO_(2) detection.Notably,NIR-RS accurately quantifies SO_(2) contents in Pinelliae rhizoma(P.rhizoma) samples,with recovery rates from 98.46 % to 102.40 %,and relative standard deviations(RSDs)< 5.0 %.For bioimaging applications,NIR-RS has low cytotoxicity and good mitochondrial-targeting ability,making it suitable for imaging exogenous and endogenous SO_(2) in mitochondria.Additionally,NIR-RS was successfully applied to image SO_(2) content of P.rhizoma samples within cells,revealing that high SO_(2) residue elevated mitochondria adenosine triphosphate(ATP) content,these findings reveal that P.rhizoma with excessive SO_(2) can affect the organism's growth mechanisms through alterations in ATP pathways.In vivo,SO_(2) was found to predominantly accumulate in the liver following gavage with P.rhizoma solution,with accumulation levels increasing in proportion to SO_(2) residue concentration.High SO_(2) concentrations in P.rhizoma can cause pulmonary fibrosis and gastric mucosal damage.This work provides a valuable tool for regulating SO_(2) content in P.rhizoma and may help researcher better understand the metabolism of SO_(2) derivatives and explore their physiological roles in biological systems.
基金National Natural Science Foundation of China (50876041)
文摘A series of computations is conducted for many multi-hole arrangements at several blowing ratios to further investigate the evolution of the film from multi-holes. The influence of multi-hole arrangement on effusion film cooling is analyzed and a preliminary relationship evaluating the film development from developing state to developed state is brought forward. Results show that the coolant jets from front rows of multi-holes merge rapidly and the strength of the kidney vortices due to mainstream-coolant jet interaction in the downstream region are mitigated under super-long-diamond arrangement where the streamwise hole-to-hole pitch is bigger than spanwise hole-to-hole pitch. The holes array arranged in super-long-diamond mode is not only in favor of obtaining developed film layer, but also improving averaged adiabatic film cooling effectiveness.
基金Sponsored by National Natural Science Foundation of China (Grant No50578049)
文摘This study firstly defines a set of arrangement rule for perforated holes of multi-hole orifice(MO), and then presents three critical geometrical parameters including total number of performated hole, equivalent diameter ratio and distribution density of perforated holes, which are to quantify MO structure. This paper built the throttling test apparatus for nice test MO plates, which were designed according to orthogonal theory. The experiments were conducted to investigate the effect of three critical geometerical parameters on the pressure loss coefficient of test MOs. Results show that equivalent diameter ratio is the dominant prameter affecting MO throttling characterstic.
基金supports of Hebei province high-tech industry multiplier project(No.16211702D)Chengde science and technology&development project(No.20152013).
文摘In order to analyze the influence of the hole chamfer on the metering performances of a Multi-hole Orifice Flowmeter and optimize the related orifice structure,a multi-hole orifice flowmeter with DN80 and throttle ratio of 0.45 was considered in the present study.The flow field characteristics were determined in the framework of a CFD technique.The results show that the multi-hole orifice flowmeter with filleting transition around the throttle orifice has higher accuracy in a wide range of the space of parameters,and is more suitable for accurate measurement of fluid in process control.
基金funded jointly by National Key Research and Development Program of China(2017YFC0804105)Fundamental Research Funds for the Central Universities of China(2015XKMS036)+1 种基金Natural Science Foundation of Jiangsu Province(BK20160245)a Project Funded by Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Conventional surface seismic exploration in areas with complex surfaces such as karst landforms has been faced with the problem of poor excitation and reception conditions.RVSP(reverse vertical seismic profile)seismic exploration adopts a geometry in which the sources are downhole and receivers are on the ground which can reduce the influence of complex surfaces on seismic wave propagation(to some extent).Through numerical simulations and real data analysis,it was noted that in areas with complex surfaces and large numbers of underground karst caves,seismic waves generated in shallow boreholes are easily affected by various surface and multiple waves as well as by scattering from karst bodies.Therefore,the quality of the reflected seismic data is extremely low.Also,it is difficult to improve the signal to noise ratio(SNR)with conventional noise filtering methods.However,when the source depth is increased,the quality of the reflected waves can be improved.This is exactly what the RVSP method accomplishes.Besides,for the RVSP method,due to its particular geometry,the apparent velocities of the reflected waves and most interference waves are quite different,which can help to filter most noise to further improve the SNR of the reflected signals.In this study,a 3 D-RVSP exploration study using 8-hole joint acquisition was conducted in a typical karst landform.The results show that the 3 D-RVSP method can obtain higher quality seismic data for complex surface conditions that have large numbers of underground karst caves.Furthermore,multi-hole joint acquisition for 3 D-RVSP has higher data collection efficiency and better uniformity of underground coverage.Therefore,in this study,38 faults were accurately revealed and at high resolution based on the 3 D-RVSP imaging results.
基金Project supported by the National Natural Science Foundation of China(Nos.51474251,51874351,and 11502226)the Natural Science Foundation of Hunan Province of China(No.2019JJ50625)and the Key Research and Development Plan of Hunan Province of China(No.2017WK2032)。
文摘Based on the elementary solutions and new integral equations,a new analytical-numerical method is proposed to calculate the interacting stresses of multiple circular holes in an infinite elastic plate under both remote stresses and arbitrarily distributed stresses applied to the circular boundaries.The validity of this new analytical-numerical method is verified by the analytical solution of the bi-harmonic stress function method,the numerical solution of the finite element method,and the analytical-numerical solutions of the series expansion and Laurent series methods.Some numerical examples are presented to investigate the effects of the hole geometry parameters(radii and relative positions)and loading conditions(remote stresses and surface stresses)on the interacting tangential stresses and interacting stress concentration factors(SCFs).The results show that whether the interference effect is shielding(k<1)or amplifying(k>1)depends on the relative orientation of holes(α)and remote stresses(σ^∞x,σ^∞y).When the maximum principal stress is aligned with the connecting line of two-hole centers andσ^∞y<0.5σ^∞x,the plate containing two circular holes has greater stability than that containing one circular hole,and the smaller circular hole has greater stability than the bigger one.This new method not only has a simple formulation and high accuracy,but also has an advantage of wide applications over common analytical methods and analytical-numerical methods in calculating the interacting stresses of a multi-hole problem under both remote and arbitrary surface stresses.
基金the National Natural Science Foundation of China(Grant No.50578049)
文摘A throttling experiment for the multi-hole orifice （MO） using water was conducted based on the conclusion of key parameters affecting the MO throttling performance. Testing MOs and standard orifice plates （ SO ） were designed for the throttling experiment to compare the throttling effect using the equivalent diameter ratio （RED） and diameter ratio （RD ） as key parameters, respectively. Meanwhile, effective metrical conditions were provided for experimental accuracy. The throttling model form was determined according to the theoretical throttling model of SO. Then the unknown parameters involved were identified by experimental data. A good concordance between the modeling computation and experimental results shows a validation of the MO throtting model.
基金Project supported by the National High Technology Research and Development Program of China (Grant No. 2008AA03Z402)the National Natural Science Foundation of China (Grant No. 61076044)the Natural Science Foundation of Beijing,China(Grant Nos. 4092007 and 4102003)
文摘A multi-hole vertical-cavity surface-emitting laser （VCSEL） operating in stable single mode with a low threshold current was produced by introducing multi-leaf scallop holes on the top distributed Bragg-refleetor of an oxidation- confined 850 nm VCSEL. The single-mode output power of 2.6 mW, threshold current of 0.6 mA, full width of half maximum lasing spectrum of less than 0.1 nm, side mode suppression ratio of 28.4 dB, and far-field divergence angle of about 10% are obtained. The effects of different hole depths on the optical characteristics are simulated and analysed, including far-field divergence, spectrum and lateral cavity mode. The single-mode performance of this multi-hole device is attributed to the large radiation loss from the inter hole spacing and the scattering loss at the bottom of the holes, particularly for higher order modes.
基金This research was funded by the National Natural Science Foundation of China(Grant No.52174113)the Young Jinggang Scholars Award Program in Jiangxi Province,China(Grant No.QNJG2018051)the“Thousand Talents”of Jiangxi Province,China(Grant No.jxsq2019201043).
文摘In the process of ion-adsorption rare earth ore leaching,the migration characteristics of the wetting front in multi-hole injection holes and the influence of wetting front intersection effect on the migration distance of wetting fronts are still unclear.Besides,wetting front migration distance and leaching time are usually required to optimize the leaching process.In this study,wetting front migration tests of ionadsorption rare earth ores during the multi-hole fluid injection(the spacing between injection holes was 10 cm,12 cm and 14 cm)and single-hole fluid injection were completed under the constant water head height.At the pre-intersection stage,the wetting front migration laws of ion-adsorption rare earth ores during the multi-hole fluid injection and single-hole fluid injection were identical.At the postintersection stage,the intersection accelerated the wetting front migration.By using the Darcy’s law,the intersection effect of wetting fronts during the multi-hole liquid injection was transformed into the water head height directly above the intersection.Finally,based on the Green-Ampt model,a wetting front migration model of ion-adsorption rare earth ores during the multi-hole unsaturated liquid injection was established.Error analysis results showed that the proposed model can accurately simulate the infiltration process under experimental conditions.The research results enrich the infiltration law and theory of ion-adsorption rare earth ores during the multi-hole liquid injection,and this study provides a scientific basis for optimizing the liquid injection well pattern parameters of ion-adsorption rare earth in situ leaching in the future.
文摘BACKGROUND Uncovered stents used for malignant obstructions in the biliary tree, especially in the hilar area, are prone to obstruction by tumor ingrowths. In comparison, however, covered stents may block bile duct branches and are at risk of migration. We have developed a multi-hole self-expandable metallic stent (MHSEMS), with a hole in each cell, to prevent the obstruction of bile duct branches. In addition, the holes may prevent migration due to small ingrowths by reducing the tension of the membrane. CASE SUMMARY MHSEMS were placed in five patients with a malignant obstruction and one with post-endoscopic sphincterotomy bleeding. Each MHSEMS was successfully deployed in all cases. Patients showed no complications. Two cases were reviewed. Case 1: A 74-year-old male presented with jaundice and was diagnosed with a sigmoid colon cancer and giant liver metastases in the right liver lobe. A MHSEMS was placed in the left bile duct. The jaundice improved and peroral cholangioscopy was performed. Case 2: A 90-year-old female was admitted to hospital for jaundice and diagnosed with cholangiocarcinoma. A MHSEMS was placed in the left bile duct but after 8 months the stent became obstructed by tumor ingrowth. We treated the patient by ablation therapy. A silicone cover separated the internal bile duct from the surrounding tissue, protecting the latter from thermal injury during treatment by endobiliary ablation of the reobstruction. CONCLUSION A MHSEMS is a new choice of stent for biliary tract diseases.
文摘Combining real accelerating genetic algorithm(RAGA) with the optimization design of multi-hole and varied diameter pipe, the authors solved the problem of optimizing multi-dimensional parameters at the same time. In which the advanced convergence and easily to run into partial optimization were avoid. Applied the RAGA to solving the problem in the optimization design of fixed piping sprinkler irrigation system. The optimized parameters, such as diameters and the length of pipe were calculated and the result was reasonable, which provides as a reference to readers who work at related research.
文摘This article provides a short review on the importance of the detailed analysis of a Langmuir probe I-V trace in a multi-Maxwellian plasma,and discuss proper procedures analyzing Langmuir probe I-V traces in bi-Maxwellian and triple-Maxwellian Electron Energy Distribution Function(EEDF)plasmas.Discus⁃sion and demonstration of procedures include the treatment of the ion saturation current,electron saturation cur⁃rent,space-charge effects on the I-V trace,and most importantly how to properly isolate and fit for each electron group present in an I-V trace reflecting a mult-Maxwellian EEDF,as well as how having a multi-Maxwellian EEDF affects the procedures of treating the ion and electron saturation currents.Shortcomings of common improp⁃er procedures are discussed and demonstrated with simulated I-V traces to show how these procedures gives false measurements.
