A new framework for drug-disease association prediction combing light-gated message passing neural network and gated fusion mechanism.

With the development of research on the complex aetiology of many diseases, computational drug repositioning methodology has proven to be a shortcut to costly and inefficient traditional methods. Therefore, developing more promising computational methods is indispensable for finding new candidate diseases to treat with existing drugs. In this paper, a model integrating a new variant of message passing neural network and a novel-gated fusion mechanism called GLGMPNN is proposed for drug-disease association prediction. First, a light-gated message passing neural network (LGMPNN), including message passing, aggregation and updating, is proposed to separately extract multiple pieces of information from the similarity networks and the association network. Then, a gated fusion mechanism consisting of a forget gate and an output gate is applied to integrate the multiple pieces of information to extent. The forget gate calculated by the multiple embeddings is built to integrate the association information into the similarity information. Furthermore, the final node representations are controlled by the output gate, which fuses the topology information of the networks and the initial similarity information. Finally, a bilinear decoder is adopted to reconstruct an adjacency matrix for drug-disease associations. Evaluated by 10-fold cross-validations, GLGMPNN achieves excellent performance compared with the current models. The following studies show that our model can effectively discover novel drug-disease associations.

Polarimetric modeling and measurement approach for refractory material in the mid-wave infrared.

Passive polarimetric imaging has gained substantial attention over the past three decades in various applications in defense. The complexity of polarimetry modeling and measurement in the thermal infrared exceeds that of the visible and near-infrared due to the complementary polarization orientation of reflected and emitted radiance. This paper presents a comprehensive polarimetric radiance model and a degree of linear polarization (DOLP) model, both of which are specifically tailored for the infrared spectrum, accounting for both reflected and emitted radiance. Building on this foundation, we conduct an analysis and simulation of the DOLP's variation as the object temperature changes. This analysis enables the observation of relationships that can be strategically utilized in subsequent experiments focused on measuring polarized model parameters. To mitigate the influence of reflected radiance components, the samples are subjected to high temperatures. The observed Stokes images from the sample surfaces are normalized to eliminate the dependence of each Stokes image on temperature. This parameters acquisition measurement method is particularly well-suited for refractories. Finally, the efficacy of the polarized model parameters acquisition technique is demonstrated through experiments involving three distinct refractory materials in the MWIR.

Bi2S3 nanorods grown on multiwalled carbon nanotubes as highly active catalysts for CO2 electroreduction to formate.

Bi-based materials are promising electrocatalysts for CO2 reduction but one of the key technological hurdles is the design of stable, active and affordable Bi-based catalysts over a wide potential range. Herein, Bi2S3/CNTs nanocomposites are constructed by anchoring bismuth sulfide (Bi2S3) nanorods onto the multiwalled carbon nanotubes (CNTs) and utilizing them in electrocatalytic CO2 reduction. CNTs, as a support, not only guarantee the conductivity and dispersibility of Bi2S3 nanorods but also improve the electrolyte infiltration and optimize the electronic structure of the Bi2S3. As expected, the Bi2S3/CNTs nanocomposite exhibits a faradaic efficiency for HCOO- (FEHCOO-) of 99.3% with a current density of -20.3 mA cm-2 at -0.91 V vs. RHE. The FEHCOO- is stably maintained at over > 91% in a wide potential window from -0.71 V to -1.31 V. Theoretical calculation analyses reveal that the strong interaction between Bi2S3 and CNTs is conductive to decreasing the energy barrier of *OCHO, stabilizing the intermediate *OCHO, and inhibiting the hydrogen evolution reaction. The current study provides an insightful understanding of the mechanism of the CO2 electroreduction reaction, and paves a new way for developing superior and affordable electrocatalysts.

River water influenced by shale gas wastewater discharge for paddy irrigation has limited effects on soil properties and microbial communities.

The processes of hydraulic fracturing to extract shale gas generate a large amount of wastewater, and the potential impacts of wastewater discharge after treatment are concerning. In this field study, we investigated the effects of the irrigation of paddy fields for 2 consecutive years by river water that has been influenced by shale gas wastewater discharge on soil physicochemical properties, microbial community structure and function, and rice grain quality. The results showed that conductivity, chloride and sulfate ions in paddy soils downstream of the outfall showed an accumulative trend after two years of irrigation, but these changes occurred on a small scale (<500 m). Two-year irrigation did not cause the accumulation of trace metals (barium, cadmium, chromium, copper, lead, strontium, zinc, nickel, and uranium) in soil and rice grains. Among all soil parameters, the accumulation of chloride ions was the most pronounced, with concentrations in the paddy soil at the discharge site 13.3 times higher than at the upstream control site. The use of influenced river water for paddy irrigation positively increased the soil microbial diversity, but these changes occurred after two years of irrigation and did not occur after one year of irrigation. Overall, the use of river water affected by shale gas wastewater discharge for agricultural irrigation has limited effects on agroecosystems over a short period. Nevertheless, the possible negative effects of contaminant accumulation in soil and rice caused by longer-term irrigation should be seriously considered.

Efficient sulfur cycling improved the performance of flowback water treatment in a microbial fuel cell.

The sulfate-reducing mediate microbial fuel cell (MFC) shows advantages in treating recalcitrant flowback water (FW) from shale gas extraction, but the stability under fluctuant concentrations of sulfate in FW remains unknown. Herein, we investigated the impact of fluctuant sulfate concentrations on the performance of FW treatment in MFCs. Sulfate concentration showed a significant role in the MFC treating FW, with a COD removal of 69.8 ± 9.7% and a peak power density of 2164 ± 396 mW/m3 under 247.5 mg/L sulfate, but only 39.1% and 1216 mW/m3 under 50 mg/L sulfate. The fluctuation of sulfate in a short time allowed to a stable performance, but a longtime intermittent decrease of feeding sulfate concentration significantly inhibited power generation to no more than 512 mW/m3. The sulfur cycling between sulfate and sulfide existed in the system, but the cycling rate became much lower after the longtime intermittent decrease, with resulting to the decreased power generation. Abundant sulfur-oxidizing bacteria (SOB) of Desulfuromonadaceae and Helicobacteraceae in the MFC stably feeding with 247.5 mg/L sulfate supported a high sulfur cycling rate. With the cooperation of abundant sulfate-reducing bacteria (SRB) of Desulfovibrionaceae (capable of producing electricity) on the anode and Desulfobacteraceae in anolyte, this sulfur cycling endowed the MFC with high sulfate tolerance and critically contributed to recalcitrant organics removal and power generation. However, much less SOB of Helicobacteraceae and Campylobacteraceae on the anode with high S0 accumulation on the surface after the longtime intermittent decrease of sulfate likely led to the low sulfur cycling rate. With also less SRB of Marinilabiaceae (capable of producing electricity) and Synergistaceae in the system, this low sulfur cycling rate thus hampered power generation. This research provides an important reference for the bioelectrochemical treatment of wastewater containing recalcitrant organics and sulfate.

Watershed-scale assessment of surface water-related risks from shale gas development in mountainous areas, China.

Water risks are one of the key issues dominating environmental debates on shale gas development. Water withdrawals and wastewater discharges in shale gas fields of mountainous areas are more complicated than in plain areas due to different climatic, topographical and hydrological conditions, which would impact water resources. This research identifies the surface water-related risks from shale gas development in mountainous areas as water shortage and water pollution. Conceptions of accessibility for both water supply and water pollution are proposed to describe the vulnerability of water resources and the exposure to water pollution. Based on a risk probability model, a water risk assessment method for mountainous areas is constructed from the perspectives of dangers, exposures and vulnerabilities. Finally, the assessment method is applied in Chongqing, China. The results show that, from 2010 to 2020, the water consumption of shale gas development has a little impact on regional water resources in total, but more significant impacts are seen in a few areas, including the seasonal water-deficient areas in Western Chongqing, the urban and suburban areas with high pollutant loadings in Midwest Chongqing, and other areas with high pollutant accessibility and vulnerable water environments. The surface water-related risks of the shale gas development in Chongqing are principally composed of low and relatively low levels of risks, which cover 60% of the total area of Chongqing and display a spatial difference of west > northeast > southeast areas. Based on Monte Carlo method, the results of uncertainty analyses show the model is reliable. This research provides a reference for water comprehensive risk assessment of shale gas development in mountainous areas.

Inhibition of benzene, toluene, phenol and benzoate in single and combination on Anammox activity: implication to the denitrification-Anammox synergy.

A previous study demonstrated that denitrification synergized with Anammox could accelerate the anaerobic degradation of benzene. The inhibitory effects of benzene, toluene, phenol and benzoate in single and combination on Anammox activity were investigated by short-term batch tests. The results indicated that the inhibition of single compounds on Anammox could be well fitted with the extended non-competitive and Luong inhibition kinetic models. The inhibitions of the individual compound were in order as follows: benzene > toluene > phenol > benzoate. The joint inhibitions of bi-component mixtures of benzene with toluene, benzene with phenol and benzene with benzoate on Anammox activity were additive; the joint inhibition of a tri-component mixture (benzene, toluene and phenol) was partly additive; and the joint inhibition of a multicomponent mixture (benzene, toluene, phenol and benzoate) was synergistic. The effect of benzoate on the denitrification-Anammox synergy for benzene degradation was evaluated using a long-term test. Although the average rate of benzene degradation decreased by 13% with the addition of 10 mg L-1 benzoate, the average rate of NO3- and NH4+ increased by approximately 1- and 0.56-fold, respectively, suggesting that benzoate favors the stability of the denitrification-Anammox synergy. The carboxylation of benzene would be a more favorable pathway for the anaerobic degradation of benzene under denitrification synergized with Anammox.

Denitrification synergized with ANAMMOX for the anaerobic degradation of benzene: performance and microbial community structure.

To evaluate the effect of anaerobic ammonium oxidation (ANAMMOX) on benzene degradation under denitrification, a sequencing batch reactor (SBR) under denitrification synergized with ANAMMOX (SBR-DenAna) for benzene degradation was established by inoculating anaerobic ammonium-oxidizing bacteria (AnAOB) into a SBR under denitrification reactor (SBR-Den) for benzene degradation. The average rate of benzene degradation and the maximum first-order kinetic constant in SBR-DenAna were 2.34- and 1.41-fold those in SBR-Den, respectively, indicating that ANAMMOX improved the degradation of benzene under denitrification synergized with ANAMMOX. However, the average rate of benzene degradation decreased by 35% in the denitrification-ANAMMOX synergistic reactor when 10 mg N L-1 NO2- was added; the rate recovered once NO2- was depleted, indicating that ANAMMOX might detoxify NO2-. Results from high-throughput sequencing analysis revealed that Azoarcus within the family Rhodocyclaceae might be associated with benzene degradation in the two SBRs. AnAOB affiliated with the family Candidatus Brocadiaceae were just detected in SBR-DenAna.

A novel anti-p21Ras scFv antibody reacting specifically with human tumour cell lines and primary tumour tissues.

BACKGROUND: The ras genes play an important role in the development and progression of human tumours. Neutralizing Ras proteins in the cytoplasm could be an effective approach to blocking ras signalling. In this study, we prepared anti-p21Ras single chain fragment variable antibody (scFv) and investigated its immunoreactivity with human tumours. METHODS: The coding sequences of H-ras, K-ras, and N-ras were separately ligated into the vector pET-28a(+). Then, recombinant expressing plasmids were induced by IPTG for p21Ras expression in E. coli. Hybridoma cell lines producing anti-p21Ras monoclonal antibodies were isolated using wildtype p21Ras proteins as immunogens. Anti-p21Ras scFv antibody was prepared from the hybridoma by the phage scFv display method. The immunoreactivity of the anti-p21Ras monoclonal antibody and the scFv antibody was identified by ELISA and immunocytochemistry. RESULTS: We prokaryotically expressed wildtype H-p21Ras, K-p21Ras and N-p21Ras and generated the hybridoma cell line KGH-R1, producing anti-p21Ras monoclonal antibodies. It was demonstrated that KGH-R1 monoclonal antibody could recognize wildtype and mutated H-p21Ras, K-p21Ras and N-p21Ras in human tumour cell lines. In all 14 types of primary human cancer tissues tested, the monoclonal antibody presented strong immunoreactivity but showed weak or negative immunoreactivity in the corresponding normal tissues. Subsequently, we prepared anti-p21Ras scFv from hybridoma KGH-R1, which showed the same immunoreactivity as the original monoclonal antibody. Sequence analysis demonstrated that the nucleotides and amino acids of the scFv exhibited an approximately 50 % difference from the anti-p21Ras scFv reported previously. CONCLUSIONS: This study presents a novel anti-p21Ras scFv antibody. Our data suggest that the scFv may be useful for ras signalling blockage and may be a potential therapeutic antibody for ras-derived tumours.

The kinetics for ammonium and nitrite oxidation under the effect of hydroxylamine.

The kinetics for ammonium (NH4(+)) oxidation and nitrite (NO2(-)) oxidation under the effect of hydroxylamine (NH2OH) were studied by respirometry using the nitrifying sludge from a laboratory-scale sequencing batch reactor. Modified models were used to estimate kinetics parameters of ammonia and nitrite oxidation under the effect of hydroxylamine. An inhibition effect of hydroxylamine on the ammonia oxidation was observed under different hydroxylamine concentration levels. The self-inhibition coefficient of hydroxylamine oxidation and noncompetitive inhibition coefficient of hydroxylamine for nitrite oxidation was estimated by simulating exogenous oxygen-uptake rate profiles, respectively. The inhibitive effect of NH2OH on nitrite-oxidizing bacteria was stronger than on ammonia-oxidizing bacteria. This work could provide fundamental data for the kinetic investigation of the nitrification process.

Shortcut nitrification-denitrification in a sequencing batch reactor by controlling aeration duration based on hydrogen ion production rate online monitoring.

The hydrogen ion production rate (HPR) and the pH of the aeration phase in a sequencing batch reactor (SBR) were simultaneously measured by a novel respirometric-titrimetric instrument. The results showed that HPR could indicate the end of ammonia oxidation with a greater accuracy and sensitivity than pH. An SBR was used to treat synthetic wastewater containing 360 mg/L chemical oxygen demand (COD) and 40 mg/L NH(4+)-N at 20 degrees C with dissolved oxygen (DO) lower than 2.0 mg/L. Controlling the aeration duration based on HPR online monitoring, shortcut nitrification-denitrification was successfully performed for approximately two months with a stable nitrite accumulation rate (NAR) above 88%, and the COD and NH(4+)-N removal ratios were both higher than 90%. Based on the HPR online monitoring data, the estimated NH(4+)-N concentrations in nitrification were closely related to the measured concentrations, with a correlation coefficient of 0.9722, and the estimated values were lower than the measured values mainly because of the titration delay at the beginning of the aeration phase.

Carboxyl and polyamine groups functionalized polyacrylonitrile fibers for efficient recovery of copper ions from solution.

Heavy metals (e.g., Cu) in wastewater are attractive resources for diverse applications, and adsorption is a promising route to recovery of heavy metals from wastewater. However, high-performance adsorbents with high adsorption capacity, speed, and stability remain challenging. Herein, chelating fibers were prepared by chemically grafting amine and carboxyl groups onto the polyacrylonitrile fiber surface and used in the wastewater's adsorption of Cu2+. The adsorption behavior of Cu2+ on the fibers was systematically investigated, and the post-adsorption fibers were comprehensively characterized to uncover the adsorption mechanism. The results show that chelated fiber has a 136.3 mg/g maximum capacity for Cu2+ adsorption at pH = 5, and the whole adsorption process could reach equilibrium in about 60 min. The adsorption process corresponds to the quasi-secondary kinetic and Langmuir models. The results of adsorption, FTIR, and XPS tests indicate that the synergistic coordination of -COOH and -NH2 plays a leading role in the rapid capture of Cu2+. In addition, introducing hydrophilic groups facilitates the rapid contact and interaction of the fibers with Cu2+ in the solution. After being used five times, the fiber's adsorption capacity remains at over 90% of its original level.

Air-plant interaction and air-soil exchange of polycyclic aromatic hydrocarbons in a large human-influenced reservoir in southwest China.

The Three Gorges Reservoir (TGR) is totally manmade, strongly influenced by anthropogenic activity, and lies on the upper reaches of Yangtze River. The periodic storage and discharge of water from the Three Gorges Dam could have altered the original air-plant/soil interactions of contaminants in TGR. Herein, paired atmospheric gas-particle, air-plant, and air-soil samples were collected to investigate the air-plant interaction and air-soil exchange of 16 USEPA priority polycyclic aromatic hydrocarbons (PAHs). The air-plant interaction based on McLachlan's framework to our datasets suggests that PAHs were absorbed via gaseous deposition that was restricted by the plant-gas dynamic equilibrium. The equilibrium indicates a dynamic balance between the gaseous phase and plant surface in PAH absorption. The main limiting factor influencing the PAH uptake was the plant species rather than the atmospheric PAH concentration. The air-soil exchange of PAHs exhibited a net volatilization flux of 16.71 ng/m2/d from the soil to the air based on annual average. There was more volatilization and less deposition in summer and more deposition and less volatilization in autumn and winter. The soil serves as a secondary source of atmospheric PAHs. As the first attempt on probing the multi-interface geochemical process of PAHs, this study highlights the influence of manual water level manipulation from the TGD and environmental factors (such as temperature, humidity, and soil properties) on the regional fate of PAHs in the TGR.

The role of TNC in atherosclerosis and drug development opportunities.

Tenascin C (TNC), a rich glycoprotein of the extracellular matrix, exhibits a pro-atherosclerosis or anti-atherosclerosis effect depending on its location. TNC, especially its C domain/isoform (TNC-C), is strongly overexpressed in atherosclerotic plaque active areas but virtually undetectable in most normal adult tissues, suggesting that TNC is a promising delivery vector target for atherosclerosis-targeted drugs. Many delivery vectors were investigated by recognizing TNC-C, including G11, G11-iRGD, TN11, PL1, and PL3. F16 and FNLM were also investigated by recognizing TNC-A1 and TNC, respectively. Notably, iRGD was undergoing clinical trials. PL1 not only recognizes TNC-C but also the extra domain-B (EDB) of fibronectin (FN), which is also a promising delivery vector for atherosclerosis-targeted drugs, and several conjugate agents are undergoing clinical trials. The F16-conjugate agent F16IL2 is undergoing clinical trials. Therefore, G11-iRGD, PL1, and F16 have great development value. Furthermore, ATN-RNA and IMA950 were investigated in clinical trials as therapeutic drugs and vaccines by targeting TNC, respectively. Therefore, targeting TNC could greatly improve the success rate of atherosclerosis-targeted drugs and/or specific drug development. This review discussed the role of TNC in atherosclerosis, atherosclerosis-targeted drug delivery vectors, and agent development to provide knowledge for drug development targeting TNC.

An EGSB-SBR based process for coupling methanogenesis and shortcut nitrogen removal.

An integrated process consisting of an anaerobic/anoxic expanded granular sludge bed (EGSB) reactor and an aerobic sequencing batch reactor (SBR) was developed by a mode of sequencing batch operation, in which methanogenesis, denitrification and anammox were coupled in EGSB with methanogenesis first, then denitrification and anammox simultaneously, and partial nitrification occurred in SBR for providing nitrite to EGSB. This process extended the application of the anammox process to the treatment of wastewater containing high concentrations of chemical oxygen demand (COD) and ammonium. When the volumetric exchange ratio between EGSB and SBR was controlled at 57% with the influent pH at 6-8, 74.38-83.65% of NH(4)(+)-N, 72.68-83.12% of total nitrogen (TN) and 88.34-98.86% of COD were removed in a range of 200-4,500 mg/L COD and 40-90 mg/L NH(4)(+)-N respectively. TN removal by anammox and shortcut denitrification was 26.35-58.64 and 0-32.80% of the removed nitrogen, respectively. The results showed that the contribution of anammox gradually decreased with an increase in the C/N ratio of influent, whereas the reverse was true for shortcut denitrification. The COD removal by methanogenesis was 70.89-98.79% of the removed COD, and increased with increasing C/N ratio.

Microbial electrosynthesis of acetate from CO2 under hypersaline conditions.

Microbial electrosynthesis (MES) enables the bioproduction of multicarbon compounds from CO2 using electricity as the driver. Although high salinity can improve the energetic performance of bioelectrochemical systems, acetogenic processes under elevated salinity are poorly known. Here MES under 35-60 g L-1 salinity was evaluated. Acetate production in two-chamber MES systems at 35 g L-1 salinity (seawater composition) gradually decreased within 60 days, both under -1.2 V cathode potential (vs. Ag/AgCl) and -1.56 A m-2 reductive current. Carbonate precipitation on cathodes (mostly CaCO3) likely declined the production through inhibiting CO2 supply, the direct electrode contact for acetogens and H2 production. Upon decreasing Ca2+ and Mg2+ levels in three-chamber reactors, acetate was stably produced over 137 days along with a low cathode apparent resistance at 1.9 ± 0.6 mΩ m2 and an average production rate at 3.80 ± 0.21 g m-2 d-1. Increasing the salinity step-wise from 35 to 60 g L-1 gave the most efficient acetate production at 40 g L-1 salinity with average rates of acetate production and CO2 consumption at 4.56 ± 3.09 and 7.02 ± 4.75 g m-2 d-1, respectively. The instantaneous coulombic efficiency for VFA averaged 55.1 ± 31.4%. Acetate production dropped at higher salinity likely due to the inhibited CO2 dissolution and acetogenic metabolism. Acetobacterium up to 78% was enriched on cathodes as the main acetogen at 35 g L-1. Under high-salinity selection, 96.5% Acetobacterium dominated on the cathode along with 34.0% Sphaerochaeta in catholyte. This research provides a first proof of concept that MES starting from CO2 reduction can be achieved at elevated salinity.

Corneal regeneration strategies: From stem cell therapy to tissue engineered stem cell scaffolds.

Corneal epithelial defects and excessive wound healing might lead to severe complications. As stem cells can self-renew infinitely, they are a promising solution for regenerating the corneal epithelium and treating severe corneal epithelial injury. The chemical and biophysical properties of biological scaffolds, such as the amniotic membrane, fibrin, and hydrogels, can provide the necessary signals for stem cell proliferation and differentiation. Multiple researchers have conducted investigations on these scaffolds and evaluated them as potential therapeutic interventions for corneal disorders. These studies have identified various inherent benefits and drawbacks associated with these scaffolds. In this study, we provided a comprehensive overview of the history and use of various stem cells in corneal repair. We mainly discussed biological scaffolds that are used in stem cell transplantation and innovative materials that are under investigation.

Nitrogen transformation promotes the anaerobic degradation of PAHs in water level fluctuation zone of the Three Gorges Reservoir in Yangtze River, China: Evidences derived from in-situ experiment.

Polycyclic aromatic hydrocarbons (PAHs) pose a great threat to human health and ecological system safety. The interception of nitrogen is common found in the riparian zone. However, there is no evidence on how nitrogen addition affects the anaerobic degradation of PAHs in soil of the water-level-fluctuation zone (WLFZ) of the Three Gorges Reservoir (TGR) in Yangtze River, China. Here, we investigated the PAHs degradation rate, the variation of key functional genes and microbial communities after nitrogen addition in soil that experienced a flooding period of water-level-fluctuation. The results revealed that the ∑16PAHs were decreased 16.19 %-36.65 % and more 3-5-rings PAHs were biodegraded with nitrogen addition in WLFZ. The most genes involved in PAHs-anaerobic degradation and denitrification were up-regulated by nitrate addition, and phyla Firmicutes, Actinobacteria and Proteobacteria were more advantages in nitrogen addition groups. The Tax4Fun based genome function analysis revealed that the microbial activity of PAHs-degradation increased with nitrate addition. The co-occurrence network analysis indicated that nitrogen addition accelerated the metabolism of nitrogen and PAHs. It is the first time to provide the direct experimental evidences that nitrogen transformation in the WLFZ soil promotes anaerobic PAHs degradation. This work is of importance to understand the effect of nitrogen intercepted in the WLFZ soil of TGR in Yangtze River, China.

Non-Negative Low-Rank Representation With Similarity Correction for Cell Type Identification in scRNA-Seq Data.

Single-cell RNA sequencing (scRNA-Seq) technology has emerged as a powerful tool to investigate cellular heterogeneity within tissues, organs, and organisms. One fundamental question pertaining to single-cell gene expression data analysis revolves around the identification of cell types, which constitutes a critical step within the data processing workflow. However, existing methods for cell type identification through learning low-dimensional latent embeddings often overlook the intercellular structural relationships. In this paper, we present a novel non-negative low-rank similarity correction model (NLRSIM) that leverages subspace clustering to preserve the global structure among cells. This model introduces a novel manifold learning process to address the issue of imbalanced neighbourhood spatial density in cells, thereby effectively preserving local geometric structures. This procedure utilizes a position-sensitive hashing algorithm to construct the graph structure of the data. The experimental results demonstrate that the NLRSIM surpasses other advanced models in terms of clustering effects and visualization experiments. The validated effectiveness of gene expression information after calibration by the NLRSIM model has been duly ascertained in the realm of relevant biological studies. The NLRSIM model offers unprecedented insights into gene expression, states, and structures at the individual cellular level, thereby contributing novel perspectives to the field.

WITHDRAWN: HCST Expression Distinguishes Immune-hot and Immune-cold Subtypes in Pancreatic Ductal Adenocarcinoma

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.