Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.

Evidence of the predominance of passive symplastic phloem loading and sugar transport with leaf ageing in Camellia oleifera

Phloem loading and transport of sugar from leaves to sink tissues such as fruits are crucial for yield formation.Camellia oleifera is an evergreen horticultural crop with high value;however,its low production limits the development of the C.oleifera industry.In this study,using a combination of ultrastructural observation,fluorescence loss in photobleaching(FLIP)and inhibitor treatment,we revealed that C.oleifera leaves mainly adopt a symplastic loading route from mesophyll cells to the surrounding vascular bundle cells in minor veins.HPLC assays showed that sucrose is the main sugar transported and only a small amount of raffinose or stachyose was detected in petioles,supporting a passive symplastic loading route in C.oleifera leaves.Compared to leaves grown this year(LT),the carbohydrate synthesis capacity in leaves grown last year(LL)was decreased while LL retained more soluble sugar,suggesting a decrease in transport capacity with leaf ageing.TEM and tissue staining showed that a reduction in plasmodesmata density leads to a decline in the degree of cellular coupling and is responsible for the weakening transport capacity in older leaves.RNA-seq revealed several differentially expressed genes(DEGs)including CoPDCB1-1,CoSUT1 and CoSWEET12,which are likely involved in the regulation of phloem loading and sugar transport.An expression correlation network is constructed between PD-callose binding protein genes,sugar transporter genes and senescence-associated genes.Collectively,this study provides the evidence of the passive symplastic phloem loading pathway in C.oleifera leaves and constructs the correlation between sugar transport and leaf ageing.

Frontiers of CO_(2)Capture and Utilization(CCU)towards Carbon Neutrality

CO_(2)capture,utilization,and storage(CCUS)technology is a rare option for the large-scale use of fossil fuels in a low-carbon way,which will definitely play a part in the journey towards carbon neutrality.Within the CCUS nexus,CCU is especially interesting because these processes will establish a new“atmosphere-to-atmosphere”carbon cycle and thus indirectly offer huge potential in carbon reduction.This study focuses on the new positioning of CCUS in the carbon neutrality scenario and aims to identify potential cutting-edge/disruptive CCU technologies that may find important application opportunities during the decarbonization of the energy and industrial system.To this end,direct air capture(DAC),flexible metal-framework materials(MOFs)for CO_(2)capture,integrated CO_(2)capture and conversion(ICCC),and electrocatalytic CO_(2)reduction(ECR)were selected,and their general introduction,the importance to carbon neutrality,and most up-to-date research progress are summarized.

Expert consensus on interventional therapy for traumatic splenic bleeding

This study aims to introduce the diagnosis and treatment processes of traumatic splenic bleeding and explain its emergency,medical,interventional,and surgical treatments.Furthermore,this study aims to summarize the indications and contraindications of splenic artery embolization,interventional procedures,and precautions of complications.

Cloning and expression analysis of a homologous expansin gene EXP2 in Picea wilsonii

Expansins are cell-wall-loosening proteins that have multiple roles during plant development and stress- related processes. In this study, a novel expansin gene PwEXP2 was cloned by rapid amplification of cDNA ends based on the cDNA library of Picea wilsonii and EST fragment of PwEXP2. It was found that PwEXP2 coded 253 amino acids, and putative signal peptides exist at the N-terminal, followed by 8 cysteines, a HFD （His-Phe-Asp） conserved domain, and 4 tryptophan residues at the C-terminal. PwEXP2 was located in cytoplasm and nucleus when transformed in an onion epidermal cell. Quantitative real-time PCR assays showed that PwEXP2 was expressed in various tissues with a relatively high level in needles and low level in mature pollen. The expression level of PwEXP2 dramatically increased after seed germination. Gene expression profiles in abiotic stresses showed that PwEXP2 was induced by high temperature and osmotic stress but not involved in ABA-dependent signaling path- way. These results display the important roles of the PwEXP2 in plant development and multiple adversity stresses.

Characterization and functional analysis of pollen-specific PwSWEET1 in Picea wilsonii

SWEET transporters play a pivotal role in sugar transport in plants.However,their functions in pollen tube growth,especially in coniferous species remain unknown.Here,we used RT-qPCR to reveal that a SWEET1 gene was specifically expressed in pollen and pollen tubes of Picea wilsonii.A pollen germination assay showed that PwSWEET1 was induced by H3BO3 but not by Ca^2+.In a sugar specificity experiment,sucrose(Suc)and glucose(Glc)were effective sugars for pollen germination and pollen tube growth.PwSWEET1 expression was induced most by Suc and Glc.Heterologous expression of PwSWEET1 in yeast showed that PwSWEET1 can restore the glucose absorption in yeast strain EBY.VW4000,which has a hexose absorption defect,and the absorption of glucose is pH-independent.This evidence supports the involvment of PwSWEET1 in boron-dependent glucose transport in pollen germination and pollen tube growth of Picea wilsonii.

Mechanism for the Self-Assembly of Hollow Micelles from Rod-Coil Block Copolymers

The mechanism for the self-assembly of hollow micelles from rod-coil diblock copolymers is proposed. In a coilselective solvent, the diblock copolymers self-assemble into a layered structure. It is assumed that the rigid rods form an elastic shell whose properties are dictated by a bending energy. For a hollow micelle, the coils outside the micelle form a brush, while the coils inside the micelle can be in two different states, a brush or an adsorption layer, corresponding to symmetric or asymmetric configurations, respectively. The total energy density of a hollow micelle is calculated by combining the interfacial energy, elastic bending energy and the stretching energy of the brushes. For the asymmetric configuration with a polymer brush on one side, the competition between the elastic bending energy and the brush stretching energy leads to a finite spontaneous curvature, stabilizing hollow spherical micelles. Comparison of the free energy density for different geometries demonstrates that transitions for the different geometry micelles are controlled by the degree of polymerization of the coils and the length of the rods. These results are in agreement with the experimental results.

Adsorption equilibrium, kinetics, and dynamic separation of Ca2+ and Mg2+ ions from phosphoric acid–nitric acid aqueous solution by strong acid cation resin

The separation of Ca2+and Mg2+ions from phosphoric acid-nitric acid aqueous solution is very significant for the neutralization process of nitrophosphate fertilizer.This paper studied the adsorption equilibrium,kinetics,and dynamic separation of Ca2+and Mg2+ions by strong acid cation resin,and the effects of phosphoric acid and nitric acid on the adsorption process were investigated.The results reveal that the adsorption process of Ca2+and Mg2+ions in pure water on resin is in good agreement with the Langmuir isotherm model and their maximal adsorption capacities are 1.86 mmol·g-1 and 1.83 mmol·g-1,respectively.The adsorption kinetics of Ca2+and Mg2+ions on resin fits better with the pseudo-first-order model,and the adsorption equilibrium in pure water is reached within 10 min contact time,while at the present of phosphoric acid,the adsorption rate of Ca2+and Mg2+ions on resin will go down.The dynamic separation experiments demonstrate that the designed column adsorption is able to undertake the separation of metal ions from the mix acids aqueous solution,but the dynamic operation should control the flow rate of mix acid solution.Besides nitric acid solution was proved to be effective to completely regenerate the spent resin and achieve the recyclable operation of separation process.

Engineered Fabrication of Enamel-Mimetic Materials

Tooth enamel,which is a biological tissue mainly composed of well-aligned hydroxyapatite nanocrystals and an interlaced protein matrix,has remarkable mechanical and aesthetic behaviors.Nevertheless,it is challenging to regenerate enamel naturally,and potential pulp involvement and tooth loss may occur.As the hardest biogenic composite material,enamel has long been regarded as a promising load-bearing material.Thus,understanding the enamel formation process and enamel structural motif mechanisms is important for the design and engineering of high-performance biomimetic composites with high strength and physical resilience.Extensive studies have been conducted on mimicking the microstructure and mechanical properties of tooth enamel,and various enamel-like material synthesis protocols have been developed.In light of the engineering fabrication of enamel-like materials,this review focuses on recent progress in synthetic strategies for enamel-mimetic materials and provides a discussion of the potential applications of these materials.

Dredging hand Yang meridians with deep tissue massage combined with neck movement in stiff-neck syndrome:A randomized controlled trial

Objective:The objective of this study is to observe the therapeutic effects of dredging hand Yang meridian with deep tissue massage combined with neck movement on stiff-neck syndrome.Materials and Methods:This is a randomized controlled trial.The consecutive patients with the stiff-neck syndrome were randomly allocated into the intervention group and patch group(1:1)according to the random number table.The intervention group was treated with dredging hand Yang meridian with deep tissue massage combined with neck movement once a day for 3 days,while the patch group therapy was treated with a 3-patch therapy and every patch included 24-h patch and 24-h patch-free.A needle electromyogram would be exerted if the patients were at their willingness in different stages.The pain of patients was assessed by Visual Analog Scale in the two groups at every 24 h time point.Results:Finally,212 patients completed the trial,106 in each group.The curative rate in the intervention group was higher than in the patch group(99.06%vs.84.91%,χ^(2)=0.890,P<0.01).Repeated measures of the general linear model showed a significant difference in pain score within the subject-factors(factor of time F=4548.577,P<0.001;factor of time-group F=490.034,P<0.001).There was a significant difference between groups regarding pain score(F=3016.315,P<0.001).Conclusion:Dredging hand Yang meridian with deep tissue massage combined with neck movement is better than patch therapy in stiff-neck syndrome,with a shorter duration and instant effects.

Effects of Different Farming Methods and Their Effects on Soil Physicochemical Properties of Guilin Maojian Tea Gardens

In order to further optimize the cultivation and agronomic technology of Guilin Maojian tea gardens, the effects, efficiencies and costs of different farming methods and their effects on the physiochemical properties of tea garden soil were studied through the modification of the test sites with the non-farming land as the control. The results showed that human farming, mini-tiller farming and crawler tractor farming could improve the physical and chemical properties of soil. After farming, the soil had good water retention but low moisture content compared to the control group, while the soil bulk density and hardness value were significantly lower than those of the control, and the porosity of soil was significantly higher than that of contrast. With the passage of time, soil bulk density and hardness value gradually increased after farming, while the porosity of soil decreased gradually. There were great differences in the effects, efficiencies and costs of different farming methods. Crawler tractor had the best and most stable farming effect, and the operation efficiency was 10 times that of human farming while the cost was only 0.39 times of human farming. Therefore, it was feasible to adopt mini-tiller or crawler tractor to carry out mechanical farming of Guilin Maojian tea garden, which provided theoretical references for the soil property improvement using mechanical farming and was favorable for promoting the popularization of farming machines and the acceleration of mechanization of tea gardens. But for tea plantations that are intended to be mechanized, apart from the mechanical and technical personnel to be configured in place, the site conditions, planting modes and mechanical way reservation of tea garden should be planned accordingly. It is recommended to select flat or gentle slope for reclamation, and preference is given to non-sexual tea tree varieties with big line spacing over 180 cm long. Moreover, the main road construction should be more than 3.0 m, and trunk road 2.0 m or above. And isolation ditch and drain should be set between the tea garden and the surrounding mountain forests and farmland.

Comparative transcriptome profiling reveals the defense pathways and mechanisms in the leaves and roots of blueberry to drought stress

Blueberry is an important horticultural plant that is very susceptible to drought.However,the molecular regulation mechanisms of blueberry tolerance to drought remain elusive.In this study,the transcriptome profile of blueberry by RNA-seq under different degrees of drought treatment were conducted and drought-related genes and pathways were screened using weighted gene co-expression network analysis(WGCNA)and Venn analysis.Interestingly,the leaves and roots of blueberry exhibited different expression patterns under drought treatment and differentially expressed genes(DEGs),GO terms and KEGG pathways were more enriched in leaves than in roots.The majority of DEGs were associated with signal transduction,transcriptional regulation,and metabolism.Eight key pathways and eight DEGs were shared both in leaves and roots.Notably,the pathway with the most core genes in leaves is the plant hormone signal transduction pathway,and in roots are the MAPK signaling pathway,reactive oxygen species metabolism and the key genes such as VcXTH3,VcPP2C51,and VcPNC1 were identified.For transcription factors,VcABR1,VcABF2,VcMYB108 and VcMYB93 are likely involved in drought response.In the metabolism category,VcCYP75A1 was likely involved in anthocyanin biosynthesis,and VcPNC1 in the monoterpenoid biosynthesis pathway.The eight DEGs markedly induced under drought exhibited differential expression in leaves and roots.Correspondingly,physiological assays showed that POD activity,ABA content,and anthocyanin biosynthesis in leaves and roots were significantly increased.Collectively,our study revealed the synergistic and distinct defense pathways and mechanisms in leaves and roots of blueberry and explored the potential regulatory network in blueberry response to drought stress.

A motion characteristics modeled angular position sensor by nonlinear transfer of differential capacitance for miniaturized scanning mirrors

In this paper,an angular position sensor(APS)designed for a resonant miniaturized scanning mirror(M-SM)is presented.The APS operates based on the principle of differential variable capacitance,significantly expanding the detectable bandwidth from a few hertz to several kilohertz.By modeling the motion characteristics,the sampling rates of the biaxial scanning angles are 1473.6 times and 539.4 times higher than those of conventional sensors.Initially,the motion characteristics model is presented as a simple harmonic motion,converting sampled capacitance into continuous capacitance.Subsequently,the nonparallel state of the M-SM and sensor is transformed into a parallel state through the space coordinate system transformation.Furthermore,a 2D nonlinear angle transfer function is developed to convert the differential capacitance into an angle,thereby mitigating the nonlinear errors resulting from large angles.Achieving an accuracy better than 0.014°,the measuring range expands from±0.5729°(±10 mrad)to±5.026°(±87 mrad).Additionally,the capturing mode and tracking mode are proposed to monitor real-time angular changes of the M-SM with an accuracy of 0.017°.High-precision APSs have enhanced beam pointing accuracy and resolution and can thereby be used to advance the development of laser components,including light detection and ranging(LiDAR).

Sarcopenia and sarcopenic obesity in patients awaiting liver transplantation

To the Editor,Sarcopenia includes the presence of both low skeletal muscle mass and low skeletal muscle function(strength and/or physical performance).A consensus definition of sarcopenia in cirrhosis patients is the phenotypic manifestation of the loss of muscle mass.1 On the basis of body composition analyses,sarcopenic obesity(SO)is defined as a combination of obesity and sarcopenia.2 Sarcopenia and SO have been detected associating with poor prognosis,including frailty,poor survival,infec-tion,and a greater length of hospital stay,physical impairment,and mortality.

NF-κB signaling in inflammation

The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses.NF-κB induces the expression of various pro-inflammatory genes,including those encoding cytokines and chemokines,and also participates in inflammasome regulation.In addition,NF-κB plays a critical role in regulating the survival,activation and differentiation of innate immune cells and inflammatory T cells.Consequently,deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases.In this review,we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.

Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver

Obesity is a major risk factor for cancers including hepatocellular carcinoma(HCC)that develops from a background of non-alcoholic fatty liver disease(NAFLD).Hypercholesterolemia is a common comorbidity of obesity.Although cholesterol biosynthesis mainly occurs in the liver,its role in HCC development of obese people remains obscure.Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models,we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T(NKT)cell-mediated antitumor immunosurveillance.Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients.Notably,cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development.Moreover,suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin(mTOR)inhibitor vistusertib preceded tumor regression,which was abolished by NKT inactivation but not CD8^(+)T cell depletion.Mechanistically,sterol regulatory element-binding protein 2(SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells,which were supported by findings in people with obesity,NAFLD and NAFLD-HCC.This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment,providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic.

Photocatalytic and Luminescent Properties of SrMoO_4 Phosphors Prepared via Hydrothermal Method with Different Stirring Speeds

To probe the potential utilities in the photocatalyst and luminescent materials, a series of SrMoO4 samples have been prepared via the hydrothermal preparation with different stirring speeds. These SrMoO4 samples were characterized using X-ray diffraction analysis, scanning electron microscopy, UV-diffuse reflection spectroscopy （UV-vis）. It has been found that the lattice parameters and [MOO4] tetrahedmn distortion of SrMoO4 samples are increased with the increased stirring speed in the process of bydrothermal preparation. By changing the stirring speeds, spindle and succulent-like morphologies have been obtained. UV-vis results show that the band gaps of SrMoO4 samples are sensitive to the stirring speed. As for the luminescent and photocatalytic properties, our experimental results clearly suggest that, compared with those samples without stirring, the luminescent and photocatalytic activities are enhanced with stirring in the hydrothermal preparation. The photodegradation of methyl blue （MB） over SrMoO4 system increases from 30% to 50%; with stirring, which may be related to small band gaps and porous surfaces. Our results indicate that stirring may he one important technique to improve the photocatalytic properties, especially in the process of hydrothermal method.

Facile fabrication of a biocompatible composite gel with sustained release of aspirin for bone regeneration

Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery.However,most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements.In the present study,we prepared a semi-interpenetrating network composite gel(CG)by incorporating short chain chitosan(CS)into a covalent tetra-armed poly(ethylene glycol)network.In addition to satisfying physicochemical,mechanics,biocompatibility,and cell affinity requirements,this CG easily encapsulated acetylsalicylic acid(ASA)via electrostatic interactions and chain entanglement,achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell(PDLSC)proliferation and osteogenic differentiation.In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model.This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1,which upregulated M2 macrophage recruitment and polarization in situ,indicating its appealing potential in bone tissue engineering.

Local conformation transitions of linear DNA induced by cisplatin

Cisplatin is the most successful anti-tumor drug,and its pharmacological property is generally considered to derive from the modification of DNA molecules.Structural modifications of short DNA induced by cisplatin have already been investigated.However,the conformation transitions induced by cisplatin are not clear.In the present letter,we have studied the effect of low-concentration cisplatin on DNA conformation by using AFM imaging.We observed formations of micro-rod structures of linear DNA induced by cisplatin.A method is presented to quantitatively analyze the occurrence of micro-rod structures.We found that the formation of micro-rod structures depends on the DNA sequence.Based on the results,we proposed a physical mechanism to explain the local conformation transitions of DNA molecules under the influence of cisplatin.

Lymphatic endothelial cells regulate B-cell homing to lymph nodes via a NIK-dependent mechanism

B cells home to the lymph nodes(LNs)via high endothelial venules(HEVs)under the guidance of chemokines,particularly CXCL13.However,as CXCL13 is not directly made in HEVs,the molecular mechanism mediating B-cell homing to LNs has remained unclear.We show here that nuclear factor(NF)-κB-inducing kinase(NIK),a kinase mediating activation of the noncanonical NF-κB pathway,functions in lymphatic endothelial cells(LECs)to regulate B-cell homing to LNs.LEC-conditional deletion of NIK in mice did not affect the integrity or global function of lymphatic vessels but caused a severe reduction in the frequency of B cells in LNs.The LEC-specific NIK deficiency did not affect the survival of B cells or the frequency of B cells in the spleen.B-cell adoptive transfer studies revealed that the LEC-specific NIK deletion impairs the ability of LNs to recruit B cells.We further show that NIK mediates expression of the chemokines CXCL13 and CCL19 in LECs.Although CCL19 is also expressed in blood endothelial cells(BECs),CXCL13 is not produced in BECs.These results suggest that NIK regulates naive B-cell homing to LNs via mediating production of the B-cell homing chemokine CXCL13 in LECs.