BACKGROUND Endoscopic retrograde appendicitis therapy(ERAT)offers an appendix-pre-serving approach;however,visual and specificity challenges persist.Conversely,endoscopic direct appendicitis therapy(EDAT)provides dire...BACKGROUND Endoscopic retrograde appendicitis therapy(ERAT)offers an appendix-pre-serving approach;however,visual and specificity challenges persist.Conversely,endoscopic direct appendicitis therapy(EDAT)provides direct visual observation with diagnostic and therapeutic capabilities.AIM To assess the efficacy and feasibility of EDAT and compare them with those of ERAT in uncomplicated appendicitis.METHODS In this retrospective cohort study,patients diagnosed with uncomplicated appendicitis and treated with ERAT or EDAT between January 2021 and November 2024 were reviewed.The primary outcome was intervention success.Secondary outcomes were guidewire use,stent placement,hospitalization duration,recurrence,and endoscopic direct-view features.Outcomes were compared between groups via appropriate statistical tests.RESULTS Of 170 patients,136 underwent EDAT and 34 ERAT.EDAT showed higher intervention success than ERAT(99.3%vs 82.4%,P<0.001),with less guidewire assistance and fewer stent placements(both P<0.001).Hospital stay was shorter with EDAT(P=0.039).The overall cumulative recurrence rates at 1 year were 10%in EDAT and 24%in ERAT;in the appendicolith subgroup,the recurrence rates were 5%and 14%in EDAT and ERAT,respectively.Findings were consistent in the propensity score-matched(PSM)cohort.CONCLUSION EDAT was demonstrated to be a more effective and feasible approach than ERAT,with a lower overall cumulative recurrence risk and within the appendicolith subgroup.Consistent results after PSM further supported the robustness of these findings.展开更多
Solar energy can be used to convert CO_(2)into valuable chemical compounds.However,the low activity of photocatalysts has hindered their development.By using defective g-C_(3)N_(4)/CeO_(2)heterojunctions,CO_(2)was suc...Solar energy can be used to convert CO_(2)into valuable chemical compounds.However,the low activity of photocatalysts has hindered their development.By using defective g-C_(3)N_(4)/CeO_(2)heterojunctions,CO_(2)was successfully photo-reduced with high performance under ambient water vapor conditions without adding additives.g-C_(3)N_(4)in this system has a significant impact on CO_(2)conversion efficiency,with 5 wt%g-C_(3)N_(4)/CeO_(2)exhibiting competitive performance,achieving 45.66 Lμmol/g CO in 6 h with nearly 100%selectivity.Photoactivity is attributed to the formation of g-C_(3)N_(4)/CeO_(2)heterojunctions,which provide excellent electron transport and electron—hole separation.Additionally,light enhances the CO_(2)adsorption capacity of the catalyst,thereby improving reaction prope rties.The photogenerated electro ns generated under light excitation can quickly gather at the surface and defective parts of the sample,facilitating effective CO_(2)adsorption and promoting the formation of *COOH,thus promoting the photoreduction process of CO_(2).Cycle tests also demonstrate long-term stability.Highly efficient charge separation and reduced free energy of CO_(2)reduction both promote CO_(2)conversion performance.This work can provide an important idea for designing CeO_(2)-based CO_(2)photocatalysts.展开更多
BACKGROUND This study analyzed the dental follicle and alveolar bone of two patients with tooth eruption disorders,aiming to provide some reference for exploring the etiology and selecting treatment plans of this dise...BACKGROUND This study analyzed the dental follicle and alveolar bone of two patients with tooth eruption disorders,aiming to provide some reference for exploring the etiology and selecting treatment plans of this disease from the perspective of the influence of extracellular matrix on osteoclasts differentiation in dental follicle.CASE SUMMARY Collect dental follicle and alveolar bone tissue from one patient with single tooth eruption disorder and one patient with full permanent tooth eruption disorder,respectively.Simultaneously collect the dental follicle and alveolar bone tissue of obstructed teeth that need to be extracted due to orthodontic treatment as the control group.Hematoxylin and eosin(HE)staining was used to observe the morphology of dental follicle cells.Immunohistochemical staining was used to observe the expression of periostin,receptor activator of nuclear factor kappa B ligand(RANKL),and osteoprotegerin(OPG)protein in dental follicle and alveolar bone tissue.And observe the eruption of teeth after removing resistance from the crown of the permanent tooth germ.CONCLUSION HE staining of two cases of dental follicle tissues showed that the volume of dental follicle cells decreased,the nuclei were condensed,and there seemed to be cellular fibrosis.The immunohistochemical staining showed that both the dental follicle and alveolar bone tissue exhibited increased expression of periostin,decreased expression of RANKL and OPG proteins,and decreased RANKL/OPG ratio.After removing resistance,the permanent tooth germ often appears to have normal eruption.Tooth eruption disorders may be accompanied by abnormal remodeling of periostin,which affects the differentiation function of osteoclasts in the dental follicle and leads to metabolic imbalance of alveolar bone,resulting in tooth eruption disorders.Whether it is a single or full permanent tooth eruption disorder,once the coronal resistance is removed,the teeth can often erupt normally.展开更多
Phosphoric acid/phosphate solu-tions are commonly used as buffer solutions in the fundamental stud-ies in electrochemistry.Informa-tion on the nature of adsorbed(bi)phosphate as well as the do-main structures is of gr...Phosphoric acid/phosphate solu-tions are commonly used as buffer solutions in the fundamental stud-ies in electrochemistry.Informa-tion on the nature of adsorbed(bi)phosphate as well as the do-main structures is of great impor-tance in unveiling the impact on electrochemical processes occur-ring at electrode electrolyte interface.In this work,the pH effect on the adsorption of phosphate related species on Pd(111)electrode has been investigated by cyclic voltammetry over a broad pH range from 1 to 14.Af-ter carefully analyzing the related onset desorption potential of(bi)phosphate adsorbate to the thermodynamic equilibrium potential of the corresponding electrode reactions,three dif-ferent phosphate related adsorbates have been identified,which are highly pH-dependent.Our analysis reveals that the dominant phosphate anions in bulk solution undergo deprotona-tion upon adsorption.At pH<1.5,the main adsorbate on Pd(111)is;H_(2)PO_(4)^(λ_(1)^(-))in solutions with 1.5<pH<7,the main adsorbate changes into.HPO_(4)^(λ_2^(-))At higher pHs,PO_(4)^(λ_(3)^(-))on electrode surface dominates.The exact charging value ofλ_(i),which represents the true va-lence of the(bi)phosphate adsorbate,could be determined using theoretical calculations.In addition,our results can not rule out the possibility of co-adsorbed H_(3)PO_(4)molecules on Pd(111)at pH<1.5,which needs to be proved by infrared spectroscopy in the future.展开更多
Background : SOX6 has been shown to play a crucial role in the development of the cardiovascular system. However, its potential role in hypertension and vascular function remains unclear. Methods : In vascular smooth ...Background : SOX6 has been shown to play a crucial role in the development of the cardiovascular system. However, its potential role in hypertension and vascular function remains unclear. Methods : In vascular smooth muscle cells(VSMCs), we employed gain-and loss-offunction approaches combined with RNA sequencing, autophagy flux assessment, and phenotype characterization. Additionally, we established a mouse model with Sox6 overexpression via adeno-associated virus 2(AAV2) to validate the findings in vivo. Results : We validated the increased expression of SOX6 in hypertension both in vitro and in vivo. Genetic silencing of Sox6 in VSMCs attenuated the phenotypic switching induced by angiotensin Ⅱ. Conversely, in vivo overexpression of Sox6 led to a significant elevation in blood pressure and promoted vascular remodeling. Mechanistically, SOX6 was shown to regulate phenotypic switching via an autophagydependent pathway. Specifically, Sox6 overexpression augmented VSMC autophagy and facilitated phenotypic switching, whereas Sox6 knockdown yielded opposite outcomes. Modulation of autophagy using 3-MA or RAPA could effectively counteract the effect mediated by SOX6. Conclusions : Our findings revealed that SOX6 regulates VSMC plasticity and elevates blood pressure by activating autophagy. Therefore, SOX6 inhibition potentially represents a novel strategy for treating hypertension and vascular remodeling.展开更多
Lung cancer is the most prevalent and fatal cancer in China and even around the world, and many patients are found in the late stage of lung cancer. For the treatment of advanced lung cancer, in addition to traditiona...Lung cancer is the most prevalent and fatal cancer in China and even around the world, and many patients are found in the late stage of lung cancer. For the treatment of advanced lung cancer, in addition to traditional chemotherapy modalities, many emerging treatments are increasingly significant, such as immunotherapy, anti-angiogenic therapy, and targeted therapy. An increasing number of studies have now shown that anti-angiogenic therapy improves the immune microenvironment by enhancing tumor immunity through normalization of tumor vessels. Immunization combined with anti-angiogenic therapy can exert synergistic effects and improve the prognosis of patients. This article summarizes the extent of benefit, current clinical study data, and future prospects of immunotherapy combined with anti-angiogenic agents in the treatment of advanced NSCLC.展开更多
Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotect...Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.展开更多
The weldability of twin-induced plasticity(TWIP)steel with ultra-high strength via friction stir welding(FSW)technique was investigated,and microstructural evolution and deformation behavior of whole and micro-zones o...The weldability of twin-induced plasticity(TWIP)steel with ultra-high strength via friction stir welding(FSW)technique was investigated,and microstructural evolution and deformation behavior of whole and micro-zones of FSW TWIP joint were studied for the first time.The results showed that the content of recrystallized grains in the stir zone(SZ)increased from 10.5%of basal material(BM)to 14.2%,and that of heat affected zone(HAZ)increased to 78.6%.The percentage of annealing twins decreased from 26.8%in BM to 11%in SZ,while increased to 35%in HAZ.Compared with the BM,the ultimate tensile strength and yield strength of the FSW joint increased to 1036 and 550 MPa,respectively,reaching 106.7%and 110.9%of BM,respectively.The elongation of the entire joint was 50.5%,which was lower than that of BM due to the nonuniform deformation during the tensile test.The engineering strain was mainly concentrated in BM and SZ and transferred to each other during the tensile test,while the engineering strain in HAZ was always the lowest.Finally,the tensile fracture occurred in the SZ.The order of ultimate tensile strength of micro-zones in the FSW joint was as follows:HAZ>BM≈SZ.The order of yield strength was as follows:HAZ>BM>SZ.展开更多
A large-scale fine-grained Mg-Gd-Y-Zn-Zr alloy plate with high strength and ductility was successfully prepared by multi-pass friction stir processing(MFSP)technology in this work.The structure of grains and long peri...A large-scale fine-grained Mg-Gd-Y-Zn-Zr alloy plate with high strength and ductility was successfully prepared by multi-pass friction stir processing(MFSP)technology in this work.The structure of grains and long period stacking ordered(LPSO)phase were characterized,and the mechanical properties uniformity was investigated.Moreover,a quantitative relationship between the microstructure and tensile yield strength was established.The results showed that the grains in the processed zone(PZ)and interfacial zone(IZ)were refined from 50μm to 3μm and 4μm,respectively,and numerous original LPSO phases were broken.In IZ,some block-shaped 18R LPSO phases were transformed into needle-like 14H LPSO phases due to stacking faults and the short-range diffusion of solute atoms.The severe shear deformation in the form of kinetic energy caused profuse stacking fault to be generated and move rapidly,greatly increasing the transformation rate of LPSO phase.After MFSP,the ultimate tensile strength,yield strength and elongation to failure of the large-scale plate were 367 MPa,305 MPa and 18.0% respectively.Grain refinement and LPSO phase strengthening were the major strengthening mechanisms for the MFSP sample.In particularly,the strength of IZ was comparable to that of PZ because the strength contribution of the 14H LPSO phase offsets the lack of grain refinement strengthening in IZ.This result opposes the widely accepted notion that IZ is a weak region in MFSP-prepared large-scale fine-grained plate.展开更多
The restoration mechanism of twin-induced plasticity(TWIP)steel during friction stir welding(FSW)changed with the degree of the deformation,and the microstructure evolution and dynamic recrystallization are complex an...The restoration mechanism of twin-induced plasticity(TWIP)steel during friction stir welding(FSW)changed with the degree of the deformation,and the microstructure evolution and dynamic recrystallization are complex and unclear.In this paper,the electron backscattered diffraction and transmission electron microscopy techniques were used to evaluate the dynamic grain structure of FSW joint of TWIP steel.The results showed that the dynamic recrystallization mechanisms in TWIP steel during FSW contained discontinuous dynamic recrystallization(DDRX)and continuous dynamic recrystallization(CDRX).The recrystallization mechanism transitioned from DDRX at the initial deformation stage to DDRX and CDRX at the middle deformation stage,eventually becoming primarily CDRX at the end deformation stage.Numerous annealing twin boundaries(ATBs)were formed within the joint,and the straight ATBs primarily resulted from grain growth accidents,while cluster-shaped ATBs were formed through re-excitations and decomposition of specific grain boundaries.展开更多
Although arbuscular mycorrhizal fungi(AMF)could play important roles in zinc(Zn)uptake in host plants,the effects of AMF on Zn uptake and transport in winter wheat during the whole growth stages remain unclear.A pot e...Although arbuscular mycorrhizal fungi(AMF)could play important roles in zinc(Zn)uptake in host plants,the effects of AMF on Zn uptake and transport in winter wheat during the whole growth stages remain unclear.A pot experiment was conducted to investigate the effects of Funneliformis mosseae(Fm)and Claroideoglomus etunicatum(Ce)on Zn absorption,transport,and accumulation in winter wheat growing in soils spiked with different Zn levels(0,2.5,and 25 mg kg^(-1)).The results showed that there was a significant correlation between mycorrhizal colonization rate and Zn absorption efficiency in winter wheat roots during the post-anthesis period,but there was no significant correlation during the pre-anthesis period.Arbuscular mycorrhizal fungi significantly increased Zn concentrations(0.56–1.58 times)in wheat grains under 0 mg kg^(-1)Zn level,but decreased Zn concentrations in wheat grains under 25 mg kg^(-1)Zn level.Additionally,at the filling and maturity stages,AMF increased Zn absorption rate and the contribution of root Zn uptake to grain Zn by 3–14 and 0.36–0.64 times,respectively,under 0 mg kg^(-1)Zn level and 0.21–1.02 and 0.27–0.37 times,respectively,under 2.5 mg kg^(-1)Zn level.However,AMF decreased root Zn absorption rate(0.32–0.61 times)and increased the contribution of Zn remobilization in vegetative tissues to grain Zn(1.69–2.01 times)under 25 mg kg^(-1)Zn level.This study would complement the mechanisms and effects of AMF on Zn absorption and transport in winter wheat and provide a potential method for the application of AMF to enrich wheat grain Zn.展开更多
Straw return in situ,a common agronomic measure in China,has been widely used not only to increase crop yields and improve soil nutrients but also to remove polycyclic aromatic hydrocarbons(PAHs)from agricultural soil...Straw return in situ,a common agronomic measure in China,has been widely used not only to increase crop yields and improve soil nutrients but also to remove polycyclic aromatic hydrocarbons(PAHs)from agricultural soils.Nevertheless,the safety risks of food crops(i.e.,human health risk of wheat grains)grown in PAHs-contaminated agricultural soils amended with crop straw remain uncertain.A pot experiment was conducted in a PAHs-contaminated agricultural soil cultivated with winter wheat under different ratios of corn straw addition(0%(control,CK),1%,2.5%,and 5%,weight/weight).Results showed that corn straw addition significantly(P<0.05)decreased PAH concentrations in rhizosphere soil,roots,straws,and grains by 48.32%–50.01%,11.85%–42.67%,9.78%–28.03%,and 14.16%–31.67%,respectively,compared with CK,whereas the transfer factors of PAHs from roots to straws were significantly(P<0.05)increased.A correlation heatmap showed that PAH concentrations in roots,straws,and grains were positively(P<0.01)correlated with those in rhizosphere soil.These indicated that corn straw decreased PAH accumulation in winter wheat due to the increase of PAH dissipation in the rhizosphere soil,although it enhanced PAH transfer in winter wheat.The incremental lifetime cancer risk(ILCR)model indicated that corn straw significantly(P<0.05)decreased the human health risk of winter wheat grains by 29.73%–45.05%.Overall,corn straw apparently reduced PAH accumulation in winter wheat,ecological risk,and human health risk via enhancing PAH dissipation in the rhizosphere soil.These findings provide an important scientific basis and theoretical guidance for agricultural safety production.展开更多
The performance of massive MIMO systems relies heavily on the availability of Channel State Information at the Transmitter(CSIT).A large amount of work has been devoted to reducing the CSIT acquisition overhead at the...The performance of massive MIMO systems relies heavily on the availability of Channel State Information at the Transmitter(CSIT).A large amount of work has been devoted to reducing the CSIT acquisition overhead at the pilot training and/or CsI feedback stage.In fact,the downlink communication generally includes three stages,i.e.,pilot training,CsI feedback,and data transmission.These three stages are mutually related and jointly determine the overall system performance.Unfortunately,there exist few studies on the reduction of csIT acquisition overhead from the global point of view.In this paper,we integrate the Minimum Mean Square Error(MMSE)channel estimation,Random Vector Quantization(RVQ)based limited feedback and Maximal Ratio Combining(MRC)precoding into a unified framework for investigating the resource allocation problem.In particular,we first approximate the covariance matrix of the quantization error with a simple expression and derive an analytical expression of the received Signal-to-Noise Ratio(SNR)based on the deterministic equivalence theory.Then the three performance metrics(the spectral efficiency,energy efficiency,and total energy consumption)oriented problems are formulated analytically.With practical system requirements,these three metrics can be collaboratively optimized.Finally,we propose an optimization solver to derive the optimal partition of channel coherence time.Experiment results verify the benefits of the proposed resource allocation schemes under three different scenarios and illustrate the tradeoff of resource allocation between three stages.展开更多
Patients who undergo adrenalectomy for unilateral primary aldosteronism(PA)may still develop post-surgery hyper-tension;however,the clinical characteristics and etiology of patients developing recurrent hypertension a...Patients who undergo adrenalectomy for unilateral primary aldosteronism(PA)may still develop post-surgery hyper-tension;however,the clinical characteristics and etiology of patients developing recurrent hypertension after adrenal-ectomy are unclear.We analyzed the records of 43 patients with recurrent elevated blood pressure after adrenalectomy,who were treated at our center.Standard routine clinical screening workup was used to identify the cause of recurrent hypertension.Causes of recurrent hypertension after adrenalectomy included essential hypertension,primary aldoster-onism,obstructive sleep apnea,renal artery stenosis,and Takayasu arteritis.Before adrenalectomy,39.5%of patients were diagnosed with confirmed or suspected PA,primarily through CT imaging.Adrenal venous sampling(AVS)tests were not conducted on any patients,and 72.1%patients underwent partial adrenalectomy.Among all patients,elevated blood pressure was observed in 44.2%immediately post-operation,18.6%within 1 month,16.3%in 1–6 months,and 20.9%>6 months after operation.Most patients had hypertension of grade 2 and above.Standard endocrine functional assessment and AVS tests should be performed before adrenalectomy to ensure more accurate diagnosis and favora-ble post-operative outcomes.Additionally,individuals often develop essential hypertension regardless of past adrenal disease.展开更多
Human induced pluripotent stem （iPS） cells are similar to embryonic stem （ES） cells, and can proliferate intensively and differentiate into a variety of cell types. However, the hepatic differentiation of human iP...Human induced pluripotent stem （iPS） cells are similar to embryonic stem （ES） cells, and can proliferate intensively and differentiate into a variety of cell types. However, the hepatic differentiation of human iPS cells has not yet been reported. In this report, human iPS cells were induced to differentiate into hepatic cells by a stepwise protocol. The expression of liver cell markers and liver-related functions of the human iPS cell-derived cells were monitored and compared with that of differentiated human ES cells and primary human hepatocytes. Approximately 60% of the differentiated human iPS cells at day 7 expressed hepatic markers alpha fetoprotein and Alb. The differentiated cells at day 21 exhibited liver cell functions including albumin Asecretion, glycogen synthesis, urea production and inducible cytochrome P450 activity. The expression of hepatic markers and fiver-related functions of the iPS cellderived hepatic ceils were comparable to that of the human ES cell-derived hepatic cells. These results show that human iPS cells, which are similar to human ES cells, can be efficiently induced to differentiate into hepatocyte-like cells.展开更多
AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple org...AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple organs of SAP rats as well as the mechanisms involved. METHODS: Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats. The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathologicalscore of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-α contents in blood. The tissue microarray was used to detect the expression levels of NF-κB p65 protein in multiple organs. RESULTS: There was no marked difference between the model group and treatment group in the survival rate. The amylase content of the treatment group was significantly lower compared to the model group at 12 h (P < 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-α levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P < 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P < 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively). Regarding the changes in liver NF-κB expression, the model group significantly exceeded the sham operation group at 3 h (P < 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P < 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-κB expression level in the treatment group significantly exceeded the model group (P < 0.05, 2.00 vs 0.00) and the sham operation group (P < 0.01, 2.00 vs 0.00) at 12 h. No NF-κB expression in the lung was found in any group. CONCLUSION: Dexamethasone can lower the amylase, endotoxin and TNF-α levels as well as mortality of SAP rats. NF-κB plays an important role in multiple organ injury. Further studies should be conducted to determine whether dexamethasone can ameliorate the pathological changes of multiple organs by reducing the NF-κB expression in the liver and kidney. The advantages of tissue microarrays in pancreatitis pathological examination include time- and energy- saving, and are highly efficient and representative. The restriction of tissue microarrays on the representation of tissues to various extents due to small diameter may lead to the deviation of analysis.展开更多
基金Supported by Guangdong Province Clinical Teaching Base Teaching Reform Research Project,No.2021JD086.
文摘BACKGROUND Endoscopic retrograde appendicitis therapy(ERAT)offers an appendix-pre-serving approach;however,visual and specificity challenges persist.Conversely,endoscopic direct appendicitis therapy(EDAT)provides direct visual observation with diagnostic and therapeutic capabilities.AIM To assess the efficacy and feasibility of EDAT and compare them with those of ERAT in uncomplicated appendicitis.METHODS In this retrospective cohort study,patients diagnosed with uncomplicated appendicitis and treated with ERAT or EDAT between January 2021 and November 2024 were reviewed.The primary outcome was intervention success.Secondary outcomes were guidewire use,stent placement,hospitalization duration,recurrence,and endoscopic direct-view features.Outcomes were compared between groups via appropriate statistical tests.RESULTS Of 170 patients,136 underwent EDAT and 34 ERAT.EDAT showed higher intervention success than ERAT(99.3%vs 82.4%,P<0.001),with less guidewire assistance and fewer stent placements(both P<0.001).Hospital stay was shorter with EDAT(P=0.039).The overall cumulative recurrence rates at 1 year were 10%in EDAT and 24%in ERAT;in the appendicolith subgroup,the recurrence rates were 5%and 14%in EDAT and ERAT,respectively.Findings were consistent in the propensity score-matched(PSM)cohort.CONCLUSION EDAT was demonstrated to be a more effective and feasible approach than ERAT,with a lower overall cumulative recurrence risk and within the appendicolith subgroup.Consistent results after PSM further supported the robustness of these findings.
基金Project supported by the National Natural Science Foundation of China (52174279)China Postdoctoral Science Foundation(2023MD734182)Yunnan Province Major Science and Technology Special Plan(202302AG050005)。
文摘Solar energy can be used to convert CO_(2)into valuable chemical compounds.However,the low activity of photocatalysts has hindered their development.By using defective g-C_(3)N_(4)/CeO_(2)heterojunctions,CO_(2)was successfully photo-reduced with high performance under ambient water vapor conditions without adding additives.g-C_(3)N_(4)in this system has a significant impact on CO_(2)conversion efficiency,with 5 wt%g-C_(3)N_(4)/CeO_(2)exhibiting competitive performance,achieving 45.66 Lμmol/g CO in 6 h with nearly 100%selectivity.Photoactivity is attributed to the formation of g-C_(3)N_(4)/CeO_(2)heterojunctions,which provide excellent electron transport and electron—hole separation.Additionally,light enhances the CO_(2)adsorption capacity of the catalyst,thereby improving reaction prope rties.The photogenerated electro ns generated under light excitation can quickly gather at the surface and defective parts of the sample,facilitating effective CO_(2)adsorption and promoting the formation of *COOH,thus promoting the photoreduction process of CO_(2).Cycle tests also demonstrate long-term stability.Highly efficient charge separation and reduced free energy of CO_(2)reduction both promote CO_(2)conversion performance.This work can provide an important idea for designing CeO_(2)-based CO_(2)photocatalysts.
基金Supported by The Xuzhou Medical University Affiliated Hospital Development Fund Support Project,No.XYFM202457the 521 Scientific Research Project of Lianyungang City,No.LYG 06521202362.
文摘BACKGROUND This study analyzed the dental follicle and alveolar bone of two patients with tooth eruption disorders,aiming to provide some reference for exploring the etiology and selecting treatment plans of this disease from the perspective of the influence of extracellular matrix on osteoclasts differentiation in dental follicle.CASE SUMMARY Collect dental follicle and alveolar bone tissue from one patient with single tooth eruption disorder and one patient with full permanent tooth eruption disorder,respectively.Simultaneously collect the dental follicle and alveolar bone tissue of obstructed teeth that need to be extracted due to orthodontic treatment as the control group.Hematoxylin and eosin(HE)staining was used to observe the morphology of dental follicle cells.Immunohistochemical staining was used to observe the expression of periostin,receptor activator of nuclear factor kappa B ligand(RANKL),and osteoprotegerin(OPG)protein in dental follicle and alveolar bone tissue.And observe the eruption of teeth after removing resistance from the crown of the permanent tooth germ.CONCLUSION HE staining of two cases of dental follicle tissues showed that the volume of dental follicle cells decreased,the nuclei were condensed,and there seemed to be cellular fibrosis.The immunohistochemical staining showed that both the dental follicle and alveolar bone tissue exhibited increased expression of periostin,decreased expression of RANKL and OPG proteins,and decreased RANKL/OPG ratio.After removing resistance,the permanent tooth germ often appears to have normal eruption.Tooth eruption disorders may be accompanied by abnormal remodeling of periostin,which affects the differentiation function of osteoclasts in the dental follicle and leads to metabolic imbalance of alveolar bone,resulting in tooth eruption disorders.Whether it is a single or full permanent tooth eruption disorder,once the coronal resistance is removed,the teeth can often erupt normally.
基金supported by the National Natural Science Foundation of China(No.22172151)。
文摘Phosphoric acid/phosphate solu-tions are commonly used as buffer solutions in the fundamental stud-ies in electrochemistry.Informa-tion on the nature of adsorbed(bi)phosphate as well as the do-main structures is of great impor-tance in unveiling the impact on electrochemical processes occur-ring at electrode electrolyte interface.In this work,the pH effect on the adsorption of phosphate related species on Pd(111)electrode has been investigated by cyclic voltammetry over a broad pH range from 1 to 14.Af-ter carefully analyzing the related onset desorption potential of(bi)phosphate adsorbate to the thermodynamic equilibrium potential of the corresponding electrode reactions,three dif-ferent phosphate related adsorbates have been identified,which are highly pH-dependent.Our analysis reveals that the dominant phosphate anions in bulk solution undergo deprotona-tion upon adsorption.At pH<1.5,the main adsorbate on Pd(111)is;H_(2)PO_(4)^(λ_(1)^(-))in solutions with 1.5<pH<7,the main adsorbate changes into.HPO_(4)^(λ_2^(-))At higher pHs,PO_(4)^(λ_(3)^(-))on electrode surface dominates.The exact charging value ofλ_(i),which represents the true va-lence of the(bi)phosphate adsorbate,could be determined using theoretical calculations.In addition,our results can not rule out the possibility of co-adsorbed H_(3)PO_(4)molecules on Pd(111)at pH<1.5,which needs to be proved by infrared spectroscopy in the future.
基金Beijing Nova Program,Grant/Award Number:20230484842National Natural Science Foundation of China,Grant/Award Number:82470461。
文摘Background : SOX6 has been shown to play a crucial role in the development of the cardiovascular system. However, its potential role in hypertension and vascular function remains unclear. Methods : In vascular smooth muscle cells(VSMCs), we employed gain-and loss-offunction approaches combined with RNA sequencing, autophagy flux assessment, and phenotype characterization. Additionally, we established a mouse model with Sox6 overexpression via adeno-associated virus 2(AAV2) to validate the findings in vivo. Results : We validated the increased expression of SOX6 in hypertension both in vitro and in vivo. Genetic silencing of Sox6 in VSMCs attenuated the phenotypic switching induced by angiotensin Ⅱ. Conversely, in vivo overexpression of Sox6 led to a significant elevation in blood pressure and promoted vascular remodeling. Mechanistically, SOX6 was shown to regulate phenotypic switching via an autophagydependent pathway. Specifically, Sox6 overexpression augmented VSMC autophagy and facilitated phenotypic switching, whereas Sox6 knockdown yielded opposite outcomes. Modulation of autophagy using 3-MA or RAPA could effectively counteract the effect mediated by SOX6. Conclusions : Our findings revealed that SOX6 regulates VSMC plasticity and elevates blood pressure by activating autophagy. Therefore, SOX6 inhibition potentially represents a novel strategy for treating hypertension and vascular remodeling.
文摘Lung cancer is the most prevalent and fatal cancer in China and even around the world, and many patients are found in the late stage of lung cancer. For the treatment of advanced lung cancer, in addition to traditional chemotherapy modalities, many emerging treatments are increasingly significant, such as immunotherapy, anti-angiogenic therapy, and targeted therapy. An increasing number of studies have now shown that anti-angiogenic therapy improves the immune microenvironment by enhancing tumor immunity through normalization of tumor vessels. Immunization combined with anti-angiogenic therapy can exert synergistic effects and improve the prognosis of patients. This article summarizes the extent of benefit, current clinical study data, and future prospects of immunotherapy combined with anti-angiogenic agents in the treatment of advanced NSCLC.
文摘Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.
基金the National Natural Science Foundation of China(Nos.52034005,52227807,52104383,and 51974220)China’s National Defense Science and Technology(173 Program)(No.2021-JCJQ-JJ-0190)+2 种基金the Shaanxi Province National Science Fund for Distinguished Young Schol-ars(No.2022JC-24)the Key Research and Development Pro-gram of Shaanxi Province(No.2020ZDLGY13-06)the Scientific Re-search Program for Youth Innovation Team Construction of Shaanxi Provincial Department of Education(No.21JP058)。
文摘The weldability of twin-induced plasticity(TWIP)steel with ultra-high strength via friction stir welding(FSW)technique was investigated,and microstructural evolution and deformation behavior of whole and micro-zones of FSW TWIP joint were studied for the first time.The results showed that the content of recrystallized grains in the stir zone(SZ)increased from 10.5%of basal material(BM)to 14.2%,and that of heat affected zone(HAZ)increased to 78.6%.The percentage of annealing twins decreased from 26.8%in BM to 11%in SZ,while increased to 35%in HAZ.Compared with the BM,the ultimate tensile strength and yield strength of the FSW joint increased to 1036 and 550 MPa,respectively,reaching 106.7%and 110.9%of BM,respectively.The elongation of the entire joint was 50.5%,which was lower than that of BM due to the nonuniform deformation during the tensile test.The engineering strain was mainly concentrated in BM and SZ and transferred to each other during the tensile test,while the engineering strain in HAZ was always the lowest.Finally,the tensile fracture occurred in the SZ.The order of ultimate tensile strength of micro-zones in the FSW joint was as follows:HAZ>BM≈SZ.The order of yield strength was as follows:HAZ>BM>SZ.
基金supported by the National Key Research and Development Program of China(2021YFB3501002)State Key Program of National Natural Science Foundation of China(5203405)+3 种基金National Natural Science Foundation of China(51974220,52104383)National Key Research and Development Program of China(2021YFB3700902)Key Research and Development Program of Shaanxi Province(2020ZDLGY13-06,2017ZDXM-GY-037)Shaanxi Province National Science Fund for Distinguished Young Scholars(2022JC-24)。
文摘A large-scale fine-grained Mg-Gd-Y-Zn-Zr alloy plate with high strength and ductility was successfully prepared by multi-pass friction stir processing(MFSP)technology in this work.The structure of grains and long period stacking ordered(LPSO)phase were characterized,and the mechanical properties uniformity was investigated.Moreover,a quantitative relationship between the microstructure and tensile yield strength was established.The results showed that the grains in the processed zone(PZ)and interfacial zone(IZ)were refined from 50μm to 3μm and 4μm,respectively,and numerous original LPSO phases were broken.In IZ,some block-shaped 18R LPSO phases were transformed into needle-like 14H LPSO phases due to stacking faults and the short-range diffusion of solute atoms.The severe shear deformation in the form of kinetic energy caused profuse stacking fault to be generated and move rapidly,greatly increasing the transformation rate of LPSO phase.After MFSP,the ultimate tensile strength,yield strength and elongation to failure of the large-scale plate were 367 MPa,305 MPa and 18.0% respectively.Grain refinement and LPSO phase strengthening were the major strengthening mechanisms for the MFSP sample.In particularly,the strength of IZ was comparable to that of PZ because the strength contribution of the 14H LPSO phase offsets the lack of grain refinement strengthening in IZ.This result opposes the widely accepted notion that IZ is a weak region in MFSP-prepared large-scale fine-grained plate.
基金supported by the National Natural Science Foundation of China(Nos.52034005,52227807,52104383,and 52222410)the Shaanxi Province National Science Fund for Distinguished Young Scholars(2022JC-24)+1 种基金the Key Research and Development Program of Shaanxi Province(2020ZDLGY13-06 and 2022JBGS2-01)the Scientific Research Program for Youth Innovation Team Construction of Shaanxi Provincial Department of Education(No.21JP058).
文摘The restoration mechanism of twin-induced plasticity(TWIP)steel during friction stir welding(FSW)changed with the degree of the deformation,and the microstructure evolution and dynamic recrystallization are complex and unclear.In this paper,the electron backscattered diffraction and transmission electron microscopy techniques were used to evaluate the dynamic grain structure of FSW joint of TWIP steel.The results showed that the dynamic recrystallization mechanisms in TWIP steel during FSW contained discontinuous dynamic recrystallization(DDRX)and continuous dynamic recrystallization(CDRX).The recrystallization mechanism transitioned from DDRX at the initial deformation stage to DDRX and CDRX at the middle deformation stage,eventually becoming primarily CDRX at the end deformation stage.Numerous annealing twin boundaries(ATBs)were formed within the joint,and the straight ATBs primarily resulted from grain growth accidents,while cluster-shaped ATBs were formed through re-excitations and decomposition of specific grain boundaries.
基金The financial support from the Natural Science Basic Research Program of Shaanxi,China(No.2023-JC-ZD17)the National Natural Science Foundation of China(Nos.42077345 and 41571456)the Project of Innovative Experimental Plan for College Students of Northwest A&F University,China(No.202310712128)。
文摘Although arbuscular mycorrhizal fungi(AMF)could play important roles in zinc(Zn)uptake in host plants,the effects of AMF on Zn uptake and transport in winter wheat during the whole growth stages remain unclear.A pot experiment was conducted to investigate the effects of Funneliformis mosseae(Fm)and Claroideoglomus etunicatum(Ce)on Zn absorption,transport,and accumulation in winter wheat growing in soils spiked with different Zn levels(0,2.5,and 25 mg kg^(-1)).The results showed that there was a significant correlation between mycorrhizal colonization rate and Zn absorption efficiency in winter wheat roots during the post-anthesis period,but there was no significant correlation during the pre-anthesis period.Arbuscular mycorrhizal fungi significantly increased Zn concentrations(0.56–1.58 times)in wheat grains under 0 mg kg^(-1)Zn level,but decreased Zn concentrations in wheat grains under 25 mg kg^(-1)Zn level.Additionally,at the filling and maturity stages,AMF increased Zn absorption rate and the contribution of root Zn uptake to grain Zn by 3–14 and 0.36–0.64 times,respectively,under 0 mg kg^(-1)Zn level and 0.21–1.02 and 0.27–0.37 times,respectively,under 2.5 mg kg^(-1)Zn level.However,AMF decreased root Zn absorption rate(0.32–0.61 times)and increased the contribution of Zn remobilization in vegetative tissues to grain Zn(1.69–2.01 times)under 25 mg kg^(-1)Zn level.This study would complement the mechanisms and effects of AMF on Zn absorption and transport in winter wheat and provide a potential method for the application of AMF to enrich wheat grain Zn.
基金supported by the National Natural Science Foundation of China(Nos.41571456 and 42077325)the Natural Science Basic Research Program of Shaanxi,China(No.2023-JC-ZD-17).
文摘Straw return in situ,a common agronomic measure in China,has been widely used not only to increase crop yields and improve soil nutrients but also to remove polycyclic aromatic hydrocarbons(PAHs)from agricultural soils.Nevertheless,the safety risks of food crops(i.e.,human health risk of wheat grains)grown in PAHs-contaminated agricultural soils amended with crop straw remain uncertain.A pot experiment was conducted in a PAHs-contaminated agricultural soil cultivated with winter wheat under different ratios of corn straw addition(0%(control,CK),1%,2.5%,and 5%,weight/weight).Results showed that corn straw addition significantly(P<0.05)decreased PAH concentrations in rhizosphere soil,roots,straws,and grains by 48.32%–50.01%,11.85%–42.67%,9.78%–28.03%,and 14.16%–31.67%,respectively,compared with CK,whereas the transfer factors of PAHs from roots to straws were significantly(P<0.05)increased.A correlation heatmap showed that PAH concentrations in roots,straws,and grains were positively(P<0.01)correlated with those in rhizosphere soil.These indicated that corn straw decreased PAH accumulation in winter wheat due to the increase of PAH dissipation in the rhizosphere soil,although it enhanced PAH transfer in winter wheat.The incremental lifetime cancer risk(ILCR)model indicated that corn straw significantly(P<0.05)decreased the human health risk of winter wheat grains by 29.73%–45.05%.Overall,corn straw apparently reduced PAH accumulation in winter wheat,ecological risk,and human health risk via enhancing PAH dissipation in the rhizosphere soil.These findings provide an important scientific basis and theoretical guidance for agricultural safety production.
基金supported by the foundation of National Key Laboratory of Electromagnetic Environment(Grant No.JCKY2020210C 614240304)Natural Science Foundation of ZheJiang province(LQY20F010001)+1 种基金the National Natural Science Foundation of China under grant numbers 82004499State Key Laboratory of Millimeter Waves under grant numbers K202012.
文摘The performance of massive MIMO systems relies heavily on the availability of Channel State Information at the Transmitter(CSIT).A large amount of work has been devoted to reducing the CSIT acquisition overhead at the pilot training and/or CsI feedback stage.In fact,the downlink communication generally includes three stages,i.e.,pilot training,CsI feedback,and data transmission.These three stages are mutually related and jointly determine the overall system performance.Unfortunately,there exist few studies on the reduction of csIT acquisition overhead from the global point of view.In this paper,we integrate the Minimum Mean Square Error(MMSE)channel estimation,Random Vector Quantization(RVQ)based limited feedback and Maximal Ratio Combining(MRC)precoding into a unified framework for investigating the resource allocation problem.In particular,we first approximate the covariance matrix of the quantization error with a simple expression and derive an analytical expression of the received Signal-to-Noise Ratio(SNR)based on the deterministic equivalence theory.Then the three performance metrics(the spectral efficiency,energy efficiency,and total energy consumption)oriented problems are formulated analytically.With practical system requirements,these three metrics can be collaboratively optimized.Finally,we propose an optimization solver to derive the optimal partition of channel coherence time.Experiment results verify the benefits of the proposed resource allocation schemes under three different scenarios and illustrate the tradeoff of resource allocation between three stages.
基金funding agency in the public,commercial,or notforprofit sectors.
文摘Patients who undergo adrenalectomy for unilateral primary aldosteronism(PA)may still develop post-surgery hyper-tension;however,the clinical characteristics and etiology of patients developing recurrent hypertension after adrenal-ectomy are unclear.We analyzed the records of 43 patients with recurrent elevated blood pressure after adrenalectomy,who were treated at our center.Standard routine clinical screening workup was used to identify the cause of recurrent hypertension.Causes of recurrent hypertension after adrenalectomy included essential hypertension,primary aldoster-onism,obstructive sleep apnea,renal artery stenosis,and Takayasu arteritis.Before adrenalectomy,39.5%of patients were diagnosed with confirmed or suspected PA,primarily through CT imaging.Adrenal venous sampling(AVS)tests were not conducted on any patients,and 72.1%patients underwent partial adrenalectomy.Among all patients,elevated blood pressure was observed in 44.2%immediately post-operation,18.6%within 1 month,16.3%in 1–6 months,and 20.9%>6 months after operation.Most patients had hypertension of grade 2 and above.Standard endocrine functional assessment and AVS tests should be performed before adrenalectomy to ensure more accurate diagnosis and favora-ble post-operative outcomes.Additionally,individuals often develop essential hypertension regardless of past adrenal disease.
基金We thank Dr Zicai Liang and Huang Huang （Institute of Molecular Medicine, Peking University） for their kind help with BioTek Multi-Detection Microplate Reader and Yizhe Zhang for technical support on real-time PCR. We also thank Chengyan Wang, Pengbo Zhang, Pingping Hou, Haisong Liu, Chun Liu and other colleagues in our laboratory for technical assistance and advice in carrying out these experiments. This study was supported by a Bill ＆ Melinda Gates Foundation Grant （37871）, a Ministry of Education grant （705001）, the National Basic Research Program of China （973 program, 2009CB522502, 2009CB941200 and 2007CB947901）, National Natural Science Foundation of China for Creative Research Groups （30421004）, the Chinese Science and Technology Key Project （2008zx10002-014, 2008zx10002- 011 and 2009ZX 10004-403） and a 111 Project to Deng H.
文摘Human induced pluripotent stem （iPS） cells are similar to embryonic stem （ES） cells, and can proliferate intensively and differentiate into a variety of cell types. However, the hepatic differentiation of human iPS cells has not yet been reported. In this report, human iPS cells were induced to differentiate into hepatic cells by a stepwise protocol. The expression of liver cell markers and liver-related functions of the human iPS cell-derived cells were monitored and compared with that of differentiated human ES cells and primary human hepatocytes. Approximately 60% of the differentiated human iPS cells at day 7 expressed hepatic markers alpha fetoprotein and Alb. The differentiated cells at day 21 exhibited liver cell functions including albumin Asecretion, glycogen synthesis, urea production and inducible cytochrome P450 activity. The expression of hepatic markers and fiver-related functions of the iPS cellderived hepatic ceils were comparable to that of the human ES cell-derived hepatic cells. These results show that human iPS cells, which are similar to human ES cells, can be efficiently induced to differentiate into hepatocyte-like cells.
基金Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province, NO. 2003C130 and NO. 2004C142 Foundation Project for Medical Science and Technology of Zhejiang province, No. 2003B134+3 种基金 Grave Foundation Project for Technological and Development of Hangzhou, No. 2003123B19 Intensive Foundation Project for Technology of Hangzhou, NO. 2004Z006 Foundation Project for Medical Science and Technology of Hangzhou, No. 2003A004 and Foundation Project for Technology of Hangzhou, No. 2005224
文摘AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple organs of SAP rats as well as the mechanisms involved. METHODS: Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats. The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathologicalscore of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-α contents in blood. The tissue microarray was used to detect the expression levels of NF-κB p65 protein in multiple organs. RESULTS: There was no marked difference between the model group and treatment group in the survival rate. The amylase content of the treatment group was significantly lower compared to the model group at 12 h (P < 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-α levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P < 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P < 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively). Regarding the changes in liver NF-κB expression, the model group significantly exceeded the sham operation group at 3 h (P < 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P < 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-κB expression level in the treatment group significantly exceeded the model group (P < 0.05, 2.00 vs 0.00) and the sham operation group (P < 0.01, 2.00 vs 0.00) at 12 h. No NF-κB expression in the lung was found in any group. CONCLUSION: Dexamethasone can lower the amylase, endotoxin and TNF-α levels as well as mortality of SAP rats. NF-κB plays an important role in multiple organ injury. Further studies should be conducted to determine whether dexamethasone can ameliorate the pathological changes of multiple organs by reducing the NF-κB expression in the liver and kidney. The advantages of tissue microarrays in pancreatitis pathological examination include time- and energy- saving, and are highly efficient and representative. The restriction of tissue microarrays on the representation of tissues to various extents due to small diameter may lead to the deviation of analysis.
