Permafrost carbon cycle and its dynamics on the Tibetan Plateau.

Our knowledge on permafrost carbon (C) cycle is crucial for understanding its feedback to climate warming and developing nature-based solutions for mitigating climate change. To understand the characteristics of permafrost C cycle on the Tibetan Plateau, the largest alpine permafrost region around the world, we summarized recent advances including the stocks and fluxes of permafrost C and their responses to thawing, and depicted permafrost C dynamics within this century. We find that this alpine permafrost region stores approximately 14.1 Pg (1 Pg=1015 g) of soil organic C (SOC) in the top 3 m. Both substantial gaseous emissions and lateral C transport occur across this permafrost region. Moreover, the mobilization of frozen C is expedited by permafrost thaw, especially by the formation of thermokarst landscapes, which could release significant amounts of C into the atmosphere and surrounding water bodies. This alpine permafrost region nevertheless remains an important C sink, and its capacity to sequester C will continue to increase by 2100. For future perspectives, we would suggest developing long-term in situ observation networks of C stocks and fluxes with improved temporal and spatial coverage, and exploring the mechanisms underlying the response of ecosystem C cycle to permafrost thaw. In addition, it is essential to improve the projection of permafrost C dynamics through in-depth model-data fusion on the Tibetan Plateau.

Metagenomic insights into microbial community structure and metabolism in alpine permafrost on the Tibetan Plateau.

Permafrost, characterized by its frozen soil, serves as a unique habitat for diverse microorganisms. Understanding these microbial communities is crucial for predicting the response of permafrost ecosystems to climate change. However, large-scale evidence regarding stratigraphic variations in microbial profiles remains limited. Here, we analyze microbial community structure and functional potential based on 16S rRNA gene amplicon sequencing and metagenomic data obtained from an ∼1000 km permafrost transect on the Tibetan Plateau. We find that microbial alpha diversity declines but beta diversity increases down the soil profile. Microbial assemblages are primarily governed by dispersal limitation and drift, with the importance of drift decreasing but that of dispersal limitation increasing with soil depth. Moreover, genes related to reduction reactions (e.g., ferric iron reduction, dissimilatory nitrate reduction, and denitrification) are enriched in the subsurface and permafrost layers. In addition, microbial groups involved in alternative electron accepting processes are more diverse and contribute highly to community-level metabolic profiles in the subsurface and permafrost layers, likely reflecting the lower redox potential and more complicated trophic strategies for microorganisms in deeper soils. Overall, these findings provide comprehensive insights into large-scale stratigraphic profiles of microbial community structure and functional potentials in permafrost regions.

Selective activation of photoactivatable fluorescent protein based on binary holography.

The ability to deliver laser doses to different target locations with high spatial and temporal resolution has been a long-sought goal in photo-stimulation and optogenetics research via, for example, photoactivatable proteins. These light-sensitive proteins undergo conformational changes upon photoactivation, serving functions such as triggering fluorescence, modulating ion channel activities, or initiating biochemical reactions within cells. Conventionally, photo-stimulation on light-sensitive proteins is performed by serially scanning a laser focus or via 2D projection, which is limited by relatively low spatiotemporal resolution. In this work, we present a programmable two-photon stimulation method based on a digital micromirror device (DMD) and binary holography to perform the activation of photoactivatable green fluorescent protein (PAGFP) in live cells. This method achieved grayscale and 3D selective PAGFP activation with subcellular resolution. In the experiments, we demonstrated the 3D activation capability and investigated the diffusion dynamics of activated PAGFP on the cell membrane. A regional difference in cell membrane diffusivity was observed, indicating the great potential of our approach in interrogating the spatiotemporal dynamics of cellular processes inside living cells.

Up-regulating GABA transporter-3 in the zona incerta prevents surgery-induced memory impairment in mice.

Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions.

MiR-625-5p is a potential therapeutic target in sepsis by regulating CXCL16/CXCR6 axis and endothelial barrier.

BACKGROUND: MicroRNA plays an important role in the progression of sepsis. We found a significant increase of in miR-625-5p expression in the blood of patients with sepsis, and lipopolysaccharide (LPS)-stimulated EA.hy926 cells. To date, little is known about the specific biological function of miR-625-5p in sepsis. METHODS: Changes in miR-625-5p expression were verified through quantitative real-time polymerase chain reaction in 45 patients with sepsis or septic shock and 30 healthy subjects. In vitro, EA.hy926 cells were treated with LPS. Transendothelial electrical resistance assay and FITC-dextran were used in evaluating endothelial barrier function. RESULTS: Herein, patients with sepsis or septic shock had significantly higher miR-625-5p expression levels, chemokine (C-X-C motif) ligand 16 (CXCL16) levels, and glycocalyx components than the healthy controls, and miR-625-5p level was positively correlated with disease. Kaplan-Meier analysis demonstrated a strong association between miR-625-5p level and 28-day mortality. Furthermore, the miR-625-5p inhibitor significantly alleviated LPS-induced endothelial barrier injury in vitro. Then, miR-625-5p positively regulated CXCL16 and down-regulated miR-625-5p attenuated CXCL16 transcription and expression in EA.hy926 cells. CXCL16 knockout significantly alleviated vascular barrier dysfunction in the LPS-induced EA.hy926 cells. sCXCL16 treatment in EA.hy926 cells significantly increased endothelial hyperpermeability by disrupting endothelial glycocalyx, tight junction proteins, and adherens junction proteins through the modulation of C-X-C chemokine receptor type 6 (CXCR6). CONCLUSIONS: Increase in miR-625-5p level may be an effective biomarker for predicting 28-day mortality in patients with sepsis/septic shock. miR-625-5p is a critical pathogenic factor for endothelial barrier dysfunction in LPS-induced EA.hy926 cells because it activates the CXCL16/CXCR6 axis.

EEF1D stabilized by SRSF9 promotes colorectal cancer via enhancing the proliferation and metastasis.

Colorectal cancer (CRC) is the third most common cancer and causes high mortality worldwide. Although CRC has been studied widely, the molecular mechanism is not completely known. Eukaryotic translation elongation factor 1 delta (EEF1D) participates in the progression of various tumors, however, the effect of EEF1D on CRC remains unclear. Here, we aimed to identify the potential mechanism of EEF1D in CRC. The expression levels of EEF1D were assessed in CRC samples. Functional analysis of EEF1D in CRC was detected in vitro and in vivo. The regulatory mechanism of EEF1D was identified with RNA immunoprecipitation, RNA pull-down assay, and proteomics analysis. Our findings confirmed that EEF1D was upregulated in human CRC tissues. Functionally, EEF1D overexpression accelerated cell proliferation and metastasis, whereas EEF1D knockdown inhibited cell proliferation and metastasis both in vitro and in vivo CRC models. Furthermore, we showed that EEF1D was upregulated by SRSF9 via binding to 3'UTR of EEF1D mRNA. EEF1D knockdown reversed the malignant phenotype induced by SRSF9 overexpression. These findings demonstrated that EEF1D promotes CRC progression, and EEF1D may be a molecular target against CRC.

Associations of incident female breast cancer with long-term exposure to PM2.5 and its constituents: Findings from a prospective cohort study in Beijing, China.

This study aimed to investigate the association between long-term exposure to fine particulate matter (PM2.5) and its constituents (black carbon (BC), ammonium (NH4+), nitrate (NO3-), organic matter (OM), inorganic sulfate (SO42-)) and incident female breast cancer in Beijing, China. Data from a prospective cohort comprising 85,504 women enrolled in the National Urban Cancer Screening Program in Beijing (2013-2019) and the Tracking Air Pollution in China dataset are used. Monthly exposures were aggregated to calculate 5-year average concentrations to indicate long-term exposure. Cox models and mixture exposure models (weighted quantile sum, quantile-based g-computation, and explanatory machine learning model) were employed to analyze the associations. Findings indicated increased levels of PM2.5 and its constituents were associated with higher breast cancer risk, with hazard ratios per 1-µg/m3 increase of 1.02 (95% confidence interval (CI): 1.01, 1.03), 1.39 (95% CI: 1.16, 1.65), 1.28 (95% CI: 1.12, 1.46), 1.15 (95% CI: 1.05, 1.24), 1.05 (95% CI: 1.02, 1.08), and 1.15 (95% CI: 1.07, 1.23) for PM2.5, BC, NH4+, NO3-, OM, and SO42-, respectively. Exposure-response curves demonstrated a monotonic risk increase without an evident threshold. Mixture exposure models highlighted BC and SO42- as key factors, underscoring the importance of reducing emissions of these pollutants.

The relationship between accommodative and binocular function with myopia progression in myopic children undergoing orthokeratology.

PURPOSE: To determine the relationship between changes in accommodative and binocular function with myopia progression in myopic children over a two-year follow-up period, and to determine when changes in visual functions stabilized after switching from spectacles to orthokeratology (Ortho-K). METHODS: This prospective, self-controlled study followed thirty-six participants (aged 8-14 years) for two years after they switched from spectacles to Ortho-K. Accommodative and binocular function were assessed prior to and 1, 3, 6, 12, 18 and 24 months after commencing Ortho-K. Measurements included accommodative amplitude, accommodative response, accommodative facility, accommodative convergence/accommodation (AC/A), ocular alignment, positive relative accommodation (PRA), negative relative accommodation (NRA), horizontal vergence range, reading ability and stereoacuity. Myopia progression was quantified by the change in axial length. RESULTS: Ocular alignment, monocular and binocular accommodative facility, and PRA stabilized after 1 month. The distance blur point in the convergence range, the distance break and recovery point in the divergence range, accommodative amplitude, calculated AC/A, stereoacuity and reading ability stabilized within 6 months. After two years of Ortho-K, NRA significantly increased (p = 0.044), while it showed no significant difference after one-year of lens wear (p = 0.49). The distance break point in the convergence range showed no significant difference (p = 0.20), but significantly decreased after one-year (p = 0.005). There were no significant correlations between the change in axial length with changes in accommodative or binocular function (p > 0.05). CONCLUSION: Accommodative and binocular function changed significantly after switching from spectacles to Ortho-K and most of the parameters stabilized within the first 6 months. There was no association between the change in accommodative or binocular function and myopia progression.

Higher disease burden and lower utilization in mongolian with breast cancer: a 9-year retrospective cohort study of 18.19 million adults in China.

BACKGROUND: Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. We aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female breast cancer patients in China. MATERIALS AND METHODS: Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. RESULTS: A total of 34,878 female patients (mean [SD] age, 52.34 [10.93] years) were included among 18.19 million Chinese, and 4,315 [12.03%] participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100,000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of breast cancer annually per capita was significantly lower for Mongolian than Han in FBC ($1,948.43 [590.11-4 776.42] vs. $2,227.35 [686.65-5,929.59], P<0.001). Mongolian females showed higher all-cause mortality (30.92, [95% CI: 28.15-33.89] vs. 27.78, [95% CI: 26.77-28.83] per 1,000, P=0.036) and breast cancer-specific mortality (18.78, [95% CI: 16.64-21.13] vs. 15.22, [95% CI: 14.47-16.00] per 1,000, P=0.002) than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality (HR, 1.21, [95% CI, 1.09-1.34]; P<0.001) and breast cancer-specific mortality (HR, 1.31, [95% CI, 1.14-1.49]; P<0.001). CONCLUSION: The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.

Using an ER-specific optogenetic mechanostimulator to understand the mechanosensitivity of the endoplasmic reticulum.

The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner. This ER Ca2+ release can be repeatedly stimulated and tuned by varying the intensity and duration of force application. Moreover, ER-specific mechanostimulation inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase the levels of binding-immunoglobulin protein (BiP) expression and phosphorylated eIF2α, two markers for ER stress. Our results provide direct evidence for ER mechanosensitivity and tight mechanoregulation of ER functions, placing ER as an important player on the intricate map of cellular mechanotransduction.

Corrective mechanisms of motion extrapolation.

Transmission and processing of sensory information in the visual system takes time. For motion perception, our brain can overcome this intrinsic neural delay through extrapolation mechanisms and accurately predict the current position of a continuously moving object. But how does the system behave when the motion abruptly changes and the prediction becomes wrong? Here we address this question by studying the perceived position of a moving object with various abrupt motion changes by human observers. We developed a task in which a bar is monotonously moving horizontally, and then motion suddenly stops, reverses, or disappears-then-reverses around two vertical stationary reference lines. Our results showed that participants overestimated the position of the stopping bar but did not perceive an overshoot in the motion reversal condition. When a temporal gap was added at the reverse point, the perceptual overshoot of the end point scaled with the gap durations. Our model suggests that the overestimation of the object position when it disappears is not linear as a function of its speeds but gradually fades out. These results can thus be reconciled in a single process where there is an interplay of the cortical motion prediction mechanisms and the late sensory transient visual inputs.

Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment.

Amultifunctional liposomal polydopamine nanoparticle (MPM@Lipo) was designed in this study, to combine chemotherapy, photothermal therapy (PTT) and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis (RA) treatment. MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia, thus contributing to the repolarization of M1 macrophages into M2 phenotype. Furthermore, MPM@Lipo could accumulate at inflammatory joints, inhibit the production of inflammatory factors, and protect cartilage in vivo, effectively alleviating RA progression in a rat adjuvant-induced arthritis model. Moreover, upon laser irradiation, MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen, resulting in excellent RA treatment effects. Overall, the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

Binocular function in the aging visual system: fusion, suppression, and stereoacuity.

Introduction: Changes in vision that occur in normal healthy aging can be seen in fundamental measures of monocular vision. However, the nature of the changes in binocular vision with age remain unclear. Methods: A total of 28 older (53-66 years) and 28 younger adults (20-31 years) were enrolled in this study. We performed a battery of tests to assess differences in monocular contrast thresholds and various binocular visual functions including dichoptic masking weight and strength, the binocular balance point for fused stimuli, and stereoacuity in the aging and control groups. Results: Aging significantly increased monocular contrast thresholds (p < 0.001). Although this suggests that aging reduces the effective "input gain" to vision, we also found a significantly elevated contribution of those weaker signals to interocular suppression (p < 0.001). Consequently, there was no significant net difference in the strength of interocular suppression (p = 0.065). We did not find a significant difference of absolute balance point between the two groups (p = 0.090). Lastly, the mean stereoacuity was worse in the older group compared to the younger group (p = 0.002). Discussion: Our findings confirm previous results showing differences in contrast sensitivity and stereoacuity with aging. Furthermore, we find a change in interocular suppression that is a possible consequence of the change in contrast sensitivity. It is suggestive of a cortical system that maintains a homeostatic balance in interocular suppression across the lifespan.

Carbon Nanofibrous Aerogels Derived from Electrospun Polyimide for Multifunctional Piezoresistive Sensors.

The fabrication of carbon aerogels with ultralow density, high electrical conductivity, and ultraelasticity still remains substantial challenges. This study utilizes electrospun polyimide aerogel as the source to fabricate flexible carbon nanofibrous aerogel (PI-CNA) capable of multifunctional applications. The lightweight PI-CNA based piezoresistive sensor shows a wide linear range (0-217 kPa), rapid response/recovery time, and fatigue resistance (12,000 cycles). More importantly, the superior pressure sensing enables the PI-CNA for all-range healthcare sensing, including pulse monitoring, physiological activity detection, speech recognition, and gait recognition. Moreover, the EMI SE and the A coefficient of the PI-CNA reach 45 dB and 0.62, respectively, indicating the outstanding absorption dominated EMI shielding effects due to the multiple reflections and absorption. Furthermore, PI-CNA exhibits satisfying Joule heating performance up to 120 °C with rapid response time (10-30 s) under low supply voltages (1.5-5 V) and possesses sufficient heating reliability and repeatability in long-term repeated heating/cooling cycles. The fabricated PI-CNA shows significant potential applications in wearable technologies, energy conversion, electronic skin, and artificial intelligence.

Force-induced tail-autotomy mitochondrial fission and biogenesis of matrix-excluded mitochondrial-derived vesicles for quality control.

Mitochondria constantly fuse and divide for mitochondrial inheritance and functions. Here, we identified a distinct type of naturally occurring fission, tail-autotomy fission, wherein a tail-like thin tubule protrudes from the mitochondrial body and disconnects, resembling autotomy. Next, utilizing an optogenetic mitochondria-specific mechanostimulator, we revealed that mechanical tensile force drives tail-autotomy fission. This force-induced fission involves DRP1/MFF and endoplasmic reticulum tubule wrapping. It redistributes mitochondrial DNA, producing mitochondrial fragments with or without mitochondrial DNA for different fates. Moreover, tensile force can decouple outer and inner mitochondrial membranes, pulling out matrix-excluded tubule segments. Subsequent tail-autotomy fission separates the matrix-excluded tubule segments into matrix-excluded mitochondrial-derived vesicles (MDVs) which recruit Parkin and LC3B, indicating the unique role of tail-autotomy fission in segregating only outer membrane components for mitophagy. Sustained force promotes fission and MDV biogenesis more effectively than transient one. Our results uncover a mechanistically and functionally distinct type of fission and unveil the role of tensile forces in modulating fission and MDV biogenesis for quality control, underscoring the heterogeneity of fission and mechanoregulation of mitochondrial dynamics.

Role of corticosteroids in the treatment of critically ill sepsis patients: a meta-analysis review.

OBJECTIVE: It was to systematically evaluate the effect of corticosteroids on 28d all-cause mortality (ACM), in-hospital death rate, and ICU death rate in critically ill sepsis patients. METHODS: PubMed, Embase, and Medline databases were used to screen the published literatures on the therapeutic effect of corticosteroids in the treatment of critically ill sepsis patients. After evaluating the quality of the included literatures, RevMan 5.3 software was used for meta-analysis. 4524 literatures regarding the application of corticosteroids to treat critically ill sepsis patients were preliminarily searched. After screening was carried out, 9 literatures were finally included. 2,850 patients were treated with corticosteroids and 2867 patients were treated with placebo. RESULTS: The meta-analysis of the effect of corticosteroids versus placebo on 28dACM showed [OR = 0.87, 95% CI 0.78-0.98, Z = 2.22, P = 0.03], P < 0.05; the meta-analysis of the outcome of corticosteroids versus placebo on ICU death rate showed [OR = 0.77, 95% CI 0.63-0.94, Z = 2.60, P = 0.009], P < 0.05; and the meta-analysis of the effect of corticosteroids versus placebo on in-hospital death rate showed [OR = 0.80, 95% CI 0.66-0.96, Z = 2.34, P = 0.002], P < 0.05. CONCLUSION: In summary, corticosteroids can reduce the death rate of critically ill sepsis patients to a certain extent and have good clinical application value.

Glutamatergic Projection from the Ventral Tegmental Area to the Zona Incerta Regulates Fear Response.

Innate defensive behavior is important for animal survival. The Vglut2+ neurons in the ventral tegmental area (VTA) have been demonstrated to play important roles in innate defensive behaviors, but the neural circuit mechanism is still unclear. Here, we find that VTA - zona incerta (ZI) glutamatergic projection is involved in regulating innate fear responses. Combining calcium signal recording and chemogentics, we find that VTA-Vglut2+ neurons respond to foot shock stimulus. Inhibition of VTA-Vglut2+ neurons reduces foot shock-evoked freezing, while chemogentic activation of these neurons results in an enhanced fear response. Using viral tracing and immunofluorescence, we show that VTA - Vglut2+ neurons send direct excitatory outputs to the ZI. Moreover, we find that the activity of VTAVglut2 - ZI projection is pivotal in modulating fear response. Together, our study reveals a new VTA - ZI glutamatergic circuit in mediating innate fear response and provides a potential target for treating post-traumatic stress disorder.

Ecological evolution of algae in connected reservoirs under the influence of water transfer: Algal density, community structure, and assembly processes.

Reservoir connectivity provides a solution for regional water shortages. Understanding the water quality of reservoirs and the response of algal communities to water transfer could provide the basis for a long-term evolutionary model of reservoirs. In this study, a water-algal community model was established to study the effects of water transfer on water quality and algal communities in reservoirs. The results showed that water transfer significantly decreased total nitrogen and nitrate concentrations. However, the water transfer resulted in an increase in the CODMn concentration and conductivity in the receiving reservoir. Additionally, the algal density and chlorophyll-a (chl-a) concentration showed an increase with water transfer. Bacillariophyta, Cyanophyta, and Chlorophyta were the dominant algal phyllum in all three reservoirs. Water transfer induced the evolution of the algal community by driving changes in the chemical parameters of the receiving reservoir and led to more complex relationships within the algal community. The effects of stochastic processes on algal communities were also enhanced in the receiving reservoirs. These results provide specific information for water quality safety management and eutrophication prevention in connected reservoirs.

Ultrasensitive Optical Detection and Elimination of Residual Microtumors with a Postoperative Implantable Hydrogel Sensor for Preventing Cancer Recurrence.

In vivo optical imaging of trace biomarkers in residual microtumors holds significant promise for cancer prognosis but poses a formidable challenge. Here, a novel hydrogel sensor is designed for ultrasensitive and specific imaging of the elusive biomarker. This hydrogel sensor seamlessly integrates a molecular beacon nanoprobe with fibroblasts, offering both high tissue retention capability and an impressive signal-to-noise ratio for imaging. Signal amplification is accomplished through exonuclease I-mediated biomarker recycling. The resulting hydrogel sensor sensitively detects the biomarker carcinoembryonic antigen with a detection limit of 1.8 pg mL-1 in test tubes. Moreover, it successfully identifies residual cancer nodules with a median diameter of less than 2 mm in mice bearing partially removed primary triple-negative breast carcinomas (4T1). Notably, this hydrogel sensor is proven effective for the sensitive diagnosis of invasive tumors in post-surgical mice with infiltrating 4T1 cells, leveraging the role of fibroblasts in locally enriching tumor cells. Furthermore, the residual microtumor is rapidly photothermal ablation by polydopamine-based nanoprobe under the guidance of visualization, achieving ≈100% suppression of tumor recurrence and lung metastasis. This work offers a promising alternative strategy for visually detecting residual microtumors, potentially enhancing the prognosis of cancer patients following surgical interventions.

Correlation of IVIM/DKI Parameters with Hypoxia Biomarkers in Fibrosarcoma Murine Models: Direct Control of MRI and Pathological Sections.

RATIONALE AND OBJECTIVES: To investigate whether intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters correlate with hypoxia biomarkers, namely hypoxia inducible factor-1ɑ (HIF-1ɑ), carbonic anhydrase IX (CAIX), and pimonidazole (PIMO), in fibrosarcoma (FS) murine models. MATERIALS AND METHODS: A model of 30 FS nude mice was established. All mice underwent magnetic resonance imaging (MRI) scans after which the IVIM (standard apparent diffusion coefficient [standard ADC], pure diffusion coefficient [D], pseudo-diffusion coefficient [D*], and perfusion fraction [f]) and DKI parameters (mean diffusion [MD], mean kurtosis [MK]) were obtained. Based on an MRI-pathology controlled method, correlations between each MRI parameter and hypoxia biomarkers were assessed by Pearson or Spearman tests. An independent sample t-test or Wilcoxon's rank sum test, and receiver operating characteristic curves were used to identify whether MRI parameters could differentiate between high and low expressions of hypoxia biomarkers. RESULTS: The IVIM/DKI parameters showed varying degrees of correlation with HIF-1α, CAIX, and PIMO expression. Among them, the D, f, and MK values could confirm HIF-1α expression, while D, f, and MK values could assess CAIX expression. Finally, standard D and MK values could evaluate PIMO expression levels. CONCLUSION: IVIM and DKI parameters can be used to reflect hypoxic biomarkers of FS and have the potential to detect tumor hypoxia.