Inflammation: Complexity and significance of cellular and molecular responses

Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.

Effects of glutamine supplementation on gut barrier,glutathione content and acute phase response in malnourished rats during inflammatory shock

AIM: To evaluate the effect of glutamine on intestinal mucosa integrity,glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP),jejunal APP mRNA levels,liver and jejunal glutathione concentrations were measured before and one,three and seven days after turpentine injection in 4 groups of control,protein-restricted,protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height,and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil,glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue,P < 0.05) in the jejunum,whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.

The relation between the response spectrum and the phase diference spectrum

The relation between the phase difference spectrum and the response spectrum is studied in this paper. It is found that the phase difference spectrum influences the response spectrum through affecting the response motion′s envelope function shape of a single degree of freedom system. Decreasing the variance of phase difference spectrum causes the increasing of response spectrum when its mean value curve keeps the same, otherwise the situation is opposite. As the increase of the tangent of the mean value curve, the response spectrum decreases, otherwise it increases. The damping plays an important role while the phase difference spectrum influences the response spectrum. The effect of the phase difference spectrum on the absolute acceleration response spectrum becomes more and more obvious with the increase of the damping. On the other hand, the increase of damping weakens the effect of the phase difference spectrum on the amplification factor spectrum.

Quantum Mechanics: Harmonic Wave-Packets, Localized by Resonant Response in Dispersion Dynamics

From a combination of Maxwell’s electromagnetism with Planck’s law and the de Broglie hypothesis, we arrive at quantized photonic wave groups whose constant phase velocity is equal to the speed of light c = ω/k and to their group velocity dω/dk. When we include special relativity expressed in simplest units, we find that, for particulate matter, the square of rest mass , i.e., angular frequency squared minus wave vector squared. This equation separates into a conservative part and a uniform responsive part. A wave function is derived in manifold rank 4, and from it are derived uncertainties and internal motion. The function solves four anomalies in quantum physics: the point particle with prescribed uncertainties;spooky action at a distance;time dependence that is consistent with the uncertainties;and resonant reduction of the wave packet by localization during measurement. A comparison between contradictory mathematical and physical theories leads to similar empirical conclusions because probability amplitudes express hidden variables. The comparison supplies orthodox postulates that are compared to physical principles that formalize the difference. The method is verified by dual harmonics found in quantized quasi-Bloch waves, where the quantum is physical;not axiomatic.

Phase composition,conductivity,and sensor properties of cerium-doped indium oxide

The hydrothermal synthesis of In_(2)O_(3)and CeO_(2)–In_(2)O_(3)is investigated as well as the properties of sensor layers based on these compounds.During the synthesis of In_(2)O_(3),intermediate products In(OH)_(3)and InOOH are formed,which are the precursors of stable cubic(c-In_(2)O_(3))and metastable rhombohedral(rh-In_(2)O_(3))phases,respectively.A transition from c-In_(2)O_(3)to rh-In_(2)O_(3)is observed with the addition of CeO_(2).The introduction of cerium into rh-In_(2)O_(3)results in a decrease in the sensor response to hydrogen,while it increases in composites based on c-In_(2)O_(3).The data on the sensor activity of the composites correlate with XPS results in which CeO_(2)causes a decrease in the concentrations of chemisorbed oxygen and oxygen vacancies in rh-In_(2)O_(3).The reverse situation is observed in composites based on c-In_(2)O_(3).Compared to In_(2)O_(3)and CeO_(2)–In_(2)O_(3)obtained by other methods,the synthesized composites demonstrate maximum response to H_(2)at low temperatures by 70–100℃,and have short response time(0.2–0.5 s),short recovery time(6–7 s),and long-term stability.A model is proposed for the dependence of sensitivity on the direction of electron transfer between In_(2)O_(3)and CeO_(2).

Diphylleia Grayi-Inspired Intelligent Temperature-Responsive Transparent Nanofiber Membranes

Nanofiber membranes(NFMs) have become attractive candidates for next-generation flexible transparent materials due to their exceptional flexibility and breathability. However, improving the transmittance of NFMs is a great challenge due to the enormous reflection and incredibly poor transmission generated by the nanofiber-air interface. In this research, we report a general strategy for the preparation of flexible temperature-responsive transparent(TRT) membranes,which achieves a rapid transformation of NFMs from opaque to highly transparent under a narrow temperature window. In this process, the phase change material eicosane is coated on the surface of the polyurethane nanofibers by electrospray technology. When the temperature rises to 37 ℃, eicosane rapidly completes the phase transition and establishes the light transmission path between the nanofibers, preventing light loss from reflection at the nanofiber-air interface. The resulting TRT membrane exhibits high transmittance(> 90%), and fast response(5 s). This study achieves the first TRT transition of NFMs, offering a general strategy for building highly transparent nanofiber materials, shaping the future of next-generation intelligent temperature monitoring, anti-counterfeiting measures, and other high-performance devices.

Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate(0.02 mg/kg) or free dexamethasone(0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide(LPS)(2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-a(TNF-a) and interleukin 6(IL-6) 2 h post-LPS and liver m RNAs and serum concentrations of the rat acute phase protein a-2-macroglobulin(a-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid effects.RESULTS: The conjugate halved the a-2-M liver m RNA(3.3 ± 0.6 vs 6.8 ± 1.1, P < 0.01) and serum protein(201 ± 48 μg/mL vs 389 ± 67 μg/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver m RNA or serum levels of a-2-M. Also, the conjugate reduced TNF-a(7208 ± 1977 pg/mL vs 21583 ± 7117 pg/mL, P = 0.03) and IL-6(15685 ± 3779 pg/mL vs 25715 ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight(421 ± 11 mg vs 465 ± 12 mg, P < 0.05) compared to controls, an effect not seen in any other group.CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo.

Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers:An open-label,non-randomized,phase II clinical trial

BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

Physical meaning and prediction efficiency of the load/unload response ratio of rocks in strain-weakening phase before failure

Rock experiment results indicate that the load/unload response ratio (LURR) of rocks expressed via strain energy may have singular or negative value after the stress in the rock reaches its maximum before rock failure or when the rock goes into the strain-weakening phase. The universality of this phenomenon is discussed. Expressed via strain or strain energy and the travel time of P wave, the variation form of the reciprocal of LURR during the process of rock failure preparation is derived. The results show that after a sharp decrease the reciprocal of LURR reaches its minimum when the main fracture of the rock is about to appear. This feature can be taken as an indication that the rock main fracture is impending.

Acute Phase Response of Rabbit to HgCl_2 and CdCl_2

A variety of changes occur in the rabbit under metal stress which include the appearance of the acute phase protein, C-reactive protein in the serum and significant reduction in the serum litres of albumin and acetylcholinesterase. The phospholipid profile is positively correlated with the higher degree of tissue necrosis encountered in mercury treated rabbit. Cadmium and mercury treatments evoke a similar response pattern in rabbit differing only in the degree of change.

Optimization of the Solid-phase Fermentation Medium of Metarhizium flavoviride by Response Surface Method

Rice flour, puparium of yellow mealworm, peanut shell and sunflower seed shell are made into the culture medium, and the optimal solid-phase fermen- tation formula for M. flavoviride is figured out. In the solid-phase fermentation, Design-Expert is applied to analyze the significance of all components on the sporu- lotion, and response surface method used to optimize the fermentation medium of M. flavoviride. The results show that puparlum of yellow mealworm is the most sig- nificant component for the sporulation; and the optimal medium formula for the fermentation of M. flavoviride： 0.25-g rice flour, 0. 14-g yellow mealworm pupari- urn, 1.00-g peanut shell, and 0.25-g sunflower seedshell. In this optimal medium, the sporulation achieves 100. 013 × 10^8 spores/mL fungal liquid, 31.7% higher than that of the initial design. Application of the optimal formula will reduce the production cost, obtain higher yield of spores, produce no pollution, and offer tech- nical support for the future large-scale production.

Elastic strain response in the modified phase-field-crystal model

To understand and develop new nanostructure materials with specific mechanical properties, a good knowledge of the elastic strain response is mandatory. Here we investigate the linear elasticity response in the modified phase-field-crystal（MPFC） model. The results show that two different propagation modes control the elastic interaction length and time, which determine whether the density waves can propagate or not. By quantitatively calculating the strain field, we find that the strain distribution is indeed extremely uniform in case of elasticity. Further, we present a detailed theoretical analysis for the orientation dependence and temperature dependence of shear modulus. The simulation results show that the shear modulus reveals strong anisotropy and the one-mode analysis provides a good guideline for determining elastic shear constants until the system temperature falls below a certain value.

Investigation of Mode and Modulation Responses in Semiconductor PS-DFB Lasers:Use of a Vector-Newton Method

A numerical model for steady state analysis and analytical expressions for the AM and FM modulation responses of DFB lasers are presented.The small signal modulation responses of 3 phase shift(PS) DFB is investigated for the first time.A new method(Vector Newton method) to obtain multiple longitudinal mode of DFB lasers is used.It is demonstrated that this method is suitable for obtaining multiple solution of high nonlinear equations.Longitudinal photon density distribution and multiple longitudinal mode of 3PS DFB and simple DFB lasers are analyzed.The results show that modulation response characteristics of 3PS DFB laser is as good as that of DFB,and PS can weaken the longitudinal spatial hole burning (LHSB) effect and is in favor of single longitudinal mode operating of lasers.

The optical nonreciprocal response based on a four-mode optomechanical system

We propose a scheme for realizing the optical nonreciprocal response based a four-mode optomechanical system,consisting of two charged mechanical modes and two linearly coupled optical modes. Two charged mechanical modes are coupled by Coulomb interaction, and two optical modes are coupled to one of mechanical modes by radiation pressure. We numerically evaluate the transmission probability of the probe field to obtain the optimum optical nonreciprocal response parameters. Also, we show that the optical nonreciprocal response is caused by the quantum interference between the optomechanical couplings and the linearly coupled interaction that breaks the time-reversal symmetry.

Hepatocellular carcinoma Liver Imaging Reporting and Data Systems treatment response assessment: Lessons learned and future directions

Hepatocellular carcinoma(HCC)is a leading cause of morbidity and mortality worldwide,with rising clinical and economic burden as incidence increases.There are a multitude of evolving treatment options,including locoregional therapies which can be used alone,in combination with each other,or in combination with systemic therapy.These treatment options have shown to be effective in achieving remission,controlling tumor progression,improving disease free and overall survival in patients who cannot undergo resection and providing a bridge to transplant by debulking tumor burden to downstage patients.Following locoregional therapy(LRT),it is crucial to provide treatment response assessment to guide management and liver transplant candidacy.Therefore,Liver Imaging Reporting and Data Systems(LI-RADS)Treatment Response Algorithm(TRA)was created to provide a standardized assessment of HCC following LRT.LIRADS TRA provides a step by step approach to evaluate each lesion independently for accurate tumor assessment.In this review,we provide an overview of different locoregional therapies for HCC,describe the expected post treatment imaging appearance following treatment,and review the LI-RADS TRA with guidance for its application in clinical practice.Unique to other publications,we will also review emerging literature supporting the use of LI-RADS for assessment of HCC treatment response after LRT.

Microstructural characteristics and paint-bake response of Al-Mg-Si-Cu alloy

The microstructural characteristics and paint-bake response of 6022 alloy with 0.3% Cu(mass fraction)were studied using optical microscope,scanning electron microscope(SEM),transmission electron microscope(TEM)and tensile tester.The results indicate that the phase constituents in the as-cast microstructure are Mg2Si,Si,Al5Cu2Mg8Si6,Al5FeSi,α-Al(MnCrFe)Si and CuAl2.During the following homogenization,CuAl2,Al5Cu2Mg8Si6 and Mg2Si phases are almost completely dissolved,and Al5FeSi transforms to α-Al(MnCrFe)Si particles.After rolling,the phase constituents in the alloy change less except the precipitation of Mg2Si particles,and the precipitation behavior of Mg2Si strongly depends on the thermomechanical conditions.Cu addition significantly increases the paint-bake response of 6022 alloy by facilitating the formation of β-" phase.Therefore,the tensile strength of 6022 alloy with 0.3% Cu is higher than that of 6022 alloy without Cu after paint-bake cycle.

ROBUST SMITH PREDICTIVE CONTROLLER FOR PROCESS WITH INVERSE RESPONSE

Smith predictor known as the time delay compensator was extended to control the process with inverse response.Modern robust control theory was employed to design the robust controller,which has only one parameter to be determined with compromise among the rise time,undershoot,robustness and capability to reject disturbance of the closed loop system.The former two specifications can be assessed quantitatively and the latter two qualitatively.Examples show that the proposed method has significant improvements and wide applicable ranges for inverse response process.

The Effect of Cardiovascular Responses after Aerobic Exercise in Menstrual Cycle

Purpose: We investigated the effect of menstrual cycle on the cardiovascular responses during recovery period from exercise. 10 healthy women were participated in the early follicular phase (EP: low estrogen and low progesterone: 1 - 4 days) and the late follicular phase (LP: high estrogen and low progesterone: 10 - 13 days) during menstrual cycle. Methods: All subjects completed a graded cycling exercise testing to determine the relative exercise intensity. All subjects were assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), and total vascular conductance (TVC) at resting and during recovery period from moderated cycling exercise during EP and LP. Results: During EP, compared with LP, resting SBP and MAP were higher and TVC was lower (p p Conclusions: This study could be increased the peripheral vasoconstriction in low estrogen levels. And during early follicular phase with low estrogen level, it may maintain an increased blood pressure during recovery period following cycling. We suggest that the timing of the menstrual cycle should be considered when measuring blood pressure during clinical exercise testing.

Effect of Lipopolysaccharide-Induced Immune Responses on Pregnancy Loss in Ewes

An acute phase response induced by Gram-negative bacteria can reduce pregnancy rate. Early pregnant ewes were used to monitor effects of lipopolysaccharide (LPS), an endotoxin in the outer cell membrane of Gram-negative bacteria, on acute phase/innate immunity response. In Exp. 1, mixed breed ewes were assigned to receive either LPS or LPS and flunixin meglumine, an inhibitor of prostaglandin synthetase, intravenously on day 5 after mating. In Exp. 2, mixed breed ewes were assigned to receive an intravenous injection on day 5 after mating of either saline, LPS, recombinant human tumor necrosis factor (TNF)-α or LPS after pretreatment with dexamethasone. Pregnancy was diagnosed ultrasonographically on d 25, and live births were recorded at parturition. Challenge with LPS induced acute phase responses (fever, mucosal responses, lethargy and increased serum TNF, haptoglobin and?serum amyloid A) and decreased pregnancy rates. Predictably, flunixin meglumine attenuated fever but did not increase pregnancy rate in LPS-treated ewes. Similarly, exogenous TNF alone induced mucosal and serum amyloid A responses but did not affect pregnancy. Pre-treatment with dexamethasone blocked fever and mucosal and lethargic responses and attenuated increases in TNF and haptoglobin but did not ameliorate LPS-induced pregnancy loss. In summary, acute challenge with LPS mimics bacterial-induced pregnancy losses in early pregnant ewes. Although pretreatment with dexamethasone decreased clinical signs and some innate immune responses, neither it nor flunixin meglumine prevented LPS-induced pregnancy loss. That exogenous TNF alone did not promote pregnancy loss indicates that other cytokines also contribute to LPS-induced embryonic loss.

Toward phase 4 trials in heart failure: A social and corporate responsibility of the medical profession

Congestive heart failure(CHF) is a chronic condition, requiring polypharmacy, allied health supports and regular monitoring. All these factors are needed to ensure compliance and to deliver the positive outcomes demonstrated from randomized controlled trials. Unfortunately many centers around the world are unable to match trial level support. The outcomes for many communities are thus unclear. Research design factors in post-marketing surveillance to address this issue. Phase 4 studies is the name given to trials designed to obtain such community level data and thus address issues of external validity. CHF phase 4 studies are relatively underutilized. We feel the onus for this research lies with the health profession. In this commentary we provide arguments as to why phase 4 studies should be viewed as a social and corporate responsibility of health professional that care for clients with CHF.