Lipocalin 2 (LCN2) confers acquired resistance to almonertinib in NSCLC through LCN2-MMP-9 signaling pathway.

Almonertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is highly selective for EGFR-activating mutations as well as the EGFR T790M mutation in patients with advanced non-small cell lung cancer (NSCLC). However, the development of resistance inevitably occurs and poses a major obstacle to the clinical efficacy of almonertinib. Therefore, a clear understanding of the mechanism is of great significance to overcome drug resistance to almonertinib in the future. In this study, NCI-H1975 cell lines resistant to almonertinib (NCI-H1975 AR) were developed by concentration-increasing induction and were employed for clarification of underlying mechanisms of acquired resistance. Through RNA-seq analysis, the HIF-1 and TGF-ß signaling pathways were significantly enriched by gene set enrichment analysis. Lipocalin-2 (LCN2), as the core node in these two signaling pathways, were found to be positively correlated to almonertinib-resistance in NSCLC cells. The function of LCN2 in the drug resistance of almonertinib was investigated through knockdown and overexpression assays in vitro and in vivo. Moreover, matrix metalloproteinases-9 (MMP-9) was further identified as a critical downstream effector of LCN2 signaling, which is regulated via the LCN2-MMP-9 axis. Pharmacological inhibition of MMP-9 could overcome resistance to almonertinib, as evidenced in both in vitro and in vivo models. Our findings suggest that LCN2 was a crucial regulator for conferring almonertinib-resistance in NSCLC and demonstrate the potential utility of targeting the LCN2-MMP-9 axis for clinical treatment of almonertinib-resistant lung adenocarcinoma.

Arenarialins A-F, Anti-inflammatory Meroterpenoids with Rearranged Skeletons from the Marine Sponge Dysidea arenaria.

Six new sesquiterpene quinone/hydroquinone meroterpenoids, arenarialins A-F (1-6), were isolated from the marine sponge Dysidea arenaria collected from the South China Sea. Their chemical structures and absolute configurations were determined by HRMS and NMR data analyses coupled with DP4+ and ECD calculations. Arenarialin A (1) features an unprecedented tetracyclic 6/6/5/6 carbon skeleton, whereas arenarialins B-D (2-4) possess two rare secomeroterpene scaffolds. Arenarialins A-F showed inhibitory activity on the production of inflammatory cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages with arenarialin D regulating the NF-κB/MAPK signaling pathway.

Enhanced Cycling and Structure Stability of an Electron Transfer-Accelerating Polymer Poly(3,4-ethylenedioxythiophene):Poly(styrenesulfonate)-Covered Mn-Based Layered Cathode with Ga3+ Doping for a Li-Ion Battery.

Mn-based cathode material Li1.20Mn0.52Ni0.20Co0.08O2 was proposed and ameliorated by surface-coating poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and doping Ga3+. X-ray diffraction and high-resolution transmission electron microscopy studies revealed that part of Ga3+ replacing the Ni site could reduce the Li+/Ni2+ mixing by forming a well-ordered layered structure and a homogeneous coating layer of PEDOT:PSS is covered on the surface of Li1.20Mn0.52Ni0.19Co0.08Ga0.01O2. The results of the electrochemical studies demonstrated the higher initial charging-discharging Coulombic efficiency, and outstanding rate capabilities and cyclic performance were obtained for the PEDOT:PSS-covered and Ga3+-doped samples. Especially, 2 wt % PEDOT:PSS-coated Li1.20Mn0.52Ni0.19Co0.08Ga0.01O2 delivered 38.3 mAh g-1, which is larger than the pristine cathode at a 5C high rate. Meanwhile, it could retain 189.6 mAh g-1 (90.3% of its initial discharge capacity at 45 °C) after 300 cycles with a 1C rate, while the pristine cathode only delivered 149.7 mAh g-1 with 80.7% cycling retention left. The results strongly suggested that such PEDOT:PSS-coated and Ga3+-doped Mn-based layered structure materials demonstrated high potential as a cathode candidate especially for high-energy applications.

Joint polarization detection and degradation mechanisms for underwater image enhancement.

Light absorption and scattering exist in the underwater environment, which can lead to blurring, reduced brightness, and color distortion in underwater images. Polarized images have the advantages of eliminating underwater scattering interference, enhancing contrast, and detecting material information of the object in underwater detection. In this paper, from the perspective of polarization imaging, different concentrations (0.15 g/ml, 0.30 g/ml, and 0.50 g/ml), different wave bands (red, green, and blue), different materials (copper, wood, high-density PVC, aluminum, cloth, foam, cloth sheet, low-density PVC, rubber, and porcelain tile), and different depths (10 cm, 20 cm, 30 cm, and 40 cm) are set up in a chamber for the experimental environment. By combining the degradation mechanism of underwater images and the analysis of polarization detection results, it is proved that the degree of polarization images have greater advantages than degree of linear polarization images, degree of circular polarization images, S1, S2, and S3 images, and visible images underwater. Finally, a fusion algorithm of underwater visible images and polarization images based on compressed sensing is proposed to enhance underwater degraded images. To improve the quality of fused images, we introduce orthogonal matching pursuit (OMP) in the high-frequency part to improve image sparsity and consistency detection in the low-frequency part to improve the image mutation phenomenon. The fusion results show that the peak SNR values of the fusion result maps using OMP in this paper are improved by 32.19% and 22.14% on average over those using backpropagation and subspace pursuit methods. With different materials and concentrations, the underwater image enhancement algorithm proposed in this paper improves information entropy, average gradient, and standard deviation by 7.76%, 18.12%, and 40.8%, respectively, on average over previous algorithms. The image NIQE value shows that the image quality obtained by this paper's algorithm is improved by about 69.26% over the original S0 image.

Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. DATA SOURCES: We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. RESULTS: Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. CONCLUSIONS: HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.

ABT-263 enhanced bacterial phagocytosis of macrophages in aged mouse through Beclin-1-dependent autophagy.

BACKGROUND: Sepsis is a critical challenge for the older adults as the immune function is less responsive by aging. Although cell numbers seem preserved in the older adults, macrophages present age-related function decline, which including reduced chemokines, phagocytosis, and autophagy. ABT-263, an inhibitor of the anti-apoptotic protein Bcl-2, is reported had a senolytic effect which can selectively clear the senescent cells in vivo and rejuvenate the aged tissues. METHODS: We treated the aged (12-16 months) and young (4-6 months) C57BL/6 mouse with ABT-263, then gave the animals cecal slurry injection to induce sepsis to observe the effect of senolytic compound ABT-263 on the survival rate of sepsis. Additionally, we isolated peritoneal macrophages from the aged mouse to investigate the cell function and molecular mechanism. 3-methyladenine (3-MA), a phosphatidylinositol 3-kinases (PI3K) inhibitor, and rapamycin, an autophagy-enhancer, were used to block or mimic the autophagy, respectively. RT-PCR and Western Blot were used to detect autophagy related gene and protein changes in sepsis. EGFP-expressing E. coli was used as a marker to evaluate the phagocytic ability of macrophages. RESULTS: The results showed ABT-263 treatment improved the survival rate of sepsis in the aged mouse which related to autophagy, while blocking the autophagy can eliminate this effect. It is revealed that ABT-263 enhanced the phagocytic ability of the peritoneal macrophages by increasing the Trem-2 receptor. Additionally, ABT-263 blocked the binding of Bcl-2 to Beclin-1, thus induced Beclin-1-dependent autophagy. CONCLUSION: ABT-263 enhanced the macrophage function in aged mouse by increasing the Trem-2 receptors and inducing a beclin-1-dependent autophagy, consequently, protected the aged mouse from sepsis.

Tanshinone IIA regulates human AML cell proliferation, cell cycle, and apoptosis through miR-497-5p/AKT3 axis.

BACKGROUND: The roots of Salvia miltiorrhiza are used in traditional Chinese medicine (TCM) and have high medicinal value. Tanshinone IIA (Tan IIA) is the active ingredient of Salvia miltiorrhiza which can inhibit the growth of acute leukemia cell lines in vitro, although the mechanism remains unclear. METHODS: CCK-8 assays and BrdU stain were used to evaluate cell proliferation ability. Western blot analysis was used to detect protein expression. miR-497-5p expression level was detected by using qRT-PCR, and Annexin V-FITC/propidium iodide (PI) was used to detect cell apoptosis. RESULTS: Here we reported that Tan IIA could inhibit cell proliferation, induce cell cycle arrest, and promote cell apoptosis in acute myeloid leukemia (AML) cells. Thus, Tan IIA had the anti-cancer activity in AML cell lines, which was likely mediated by up-regulation of miR-497-5p expression. Our data further showed that in AML cells, the same effects were observed with overexpression of miR-497-5p by a miR-497-5p mimic. We demonstrated that Tan IIA could inhibit the expression of AKT3 by up-regulating the expression of miR-497-5p. We subsequently identified that AKT3 was the direct target of miR-497-5p, and that treatment with Tan IIA obviously reversed the effect of treatment with an miR-497-5p inhibitor under harsh conditions. In turn, PCNA expression was increased and cleaved Caspase-3 was suppressed, which contributed to the growth of AML cells. CONCLUSIONS: Our results showed that Tan IIA could inhibit cell proliferation in AML cells through miR-497-5p-mediated AKT3 downregulation pathway.

Identification of HSP90 as a direct target of artemisinin for its anti-inflammatory activity via quantitative chemical proteomics.

The anti-malarial drug artemisinin (ART) possesses potent anti-inflammatory activity, yet its underlying mechanism of action has remained elusive. Here we employed quantitative chemical proteomics to in situ profile the cellular targets of ART and identified heat shock protein 90 (HSP90) as a direct target. Further study revealed that ART suppressed the production of nitric oxide (NO) in macrophages via inhibiting the interaction between HSP90 and inducible NO synthase (iNOS).

[Research advances in endogenous neural stem cells promoting neural repair after ischemic stroke].

Neural stem cell therapy, as a new therapeutic method for neural diseases, has aroused a wide concern for over 20 years since neural stem cells were first found in 1992. Ischemic stroke is highly concerned because of its high incidence, mortality and disability rates. Because the brain has a limited ability to repair itself, to improve neural function and promote neural regeneration may help to prevent occurrence and development of neurological diseases. It is noteworthy that some stroke patients showed an ability to repair brain several months after the stroke happened, suggesting an existence of endogenous nerve repair in these patients. The research advances in functions of endogenous neural stem cells in neural regeneration and the related regulators after ischemic stroke are summarized in this review to provide new views of the mechanism of neural functional recovery after ischemic stroke.

Third-Order Nonlinear Optical Properties of InN Thin Films Under 532 nm Nanosecond Laser Pulses.

In order to investigate the third-order nonlinear optical properties of InN thin film, the sample was deposited on sapphire substrates by reactive RF magnetron sputtering. The prepared samples with a hexagonal wurtzite structure were confirmed by both X-ray diffraction (XRD) and scanning electron microscope (SEM). The optical absorption spectrum of the prepared samples was measured by a double beam UV/Visible spectrophotometer. The results show that the optical bandgap of deposited thin film is 2.06 eV. The third-order nonlinear optical coefficients of the film were measured by using the open and closed aperture transmission Z-scan (TZ-scan) technique under nanosecond laser pulses with a wavelength of 532 nm. The test results show that the prepared InN thin film performs strong saturation absorption, and the InN thin film with positive nonlinear refractive index coefficient is the self-focusing material under the conditions of the nanosecond laser pulses with the photon energy larger than the bandgap of prepared samples.

Enhancement in Tonically Active Glutamatergic Inputs to the Rostral Ventrolateral Medulla Contributes to Neuropathic Pain-Induced High Blood Pressure.

Neuropathic pain increases the risk of cardiovascular diseases including hypertension with the characteristic of sympathetic overactivity. The enhanced tonically active glutamatergic input to the rostral ventrolateral medulla (RVLM) contributes to sympathetic overactivity and blood pressure (BP) in cardiovascular diseases. We hypothesize that neuropathic pain enhances tonically active glutamatergic inputs to the RVLM, which contributes to high level of BP and sympathetic outflow. Animal model with the trigeminal neuropathic pain was induced by the infraorbital nerve-chronic constriction injury (ION-CCI). A significant increase in BP and renal sympathetic nerve activity (RSNA) was found in rats with ION-CCI (BP, n = 5, RSNA, n = 7, p < 0.05). The concentration of glutamate in the RVLM was significantly increased in the ION-CCI group (n = 4, p < 0.05). Blockade of glutamate receptors by injection of kynurenic acid into the RVLM significantly decreased BP and RSNA in the ION-CCI group (n = 5, p < 0.05). In two major sources (the paraventricular nucleus and periaqueductal gray) for glutamatergic inputs to the RVLM, the ION-CCI group (n = 5, p < 0.05) showed an increase in glutamate content and expression of glutaminase 2, vesicular glutamate transporter 2 proteins, and c-fos. Our results suggest that enhancement in tonically active glutamatergic inputs to the RVLM contributes to neuropathic pain-induced high blood pressure.

Effect of Organic Matter on Sorption of Zn on Soil: Elucidation by Wien Effect Measurements and EXAFS Spectroscopy.

Soil organic matter (SOM) is the major factor affecting sequestration of heavy metals in soil. The mean free binding energy and the mean free adsorption energy and speciation of Zn in soil, as affected by SOM, were determined by employing Wien effect measurements. The presence of SOM markedly decreased the Zn binding energy in soils in the following order: Top (5.86 kJ mol(-1)) < Bottom (8.66 kJ mol(-1)) < Top OM-free (9.44 kJ mol(-1)) ≈ Bottom OM-free (9.50 kJ mol(-1)). The SOM also significantly decreased the adsorption energy of Zn on black soil particles by reducing nonspecific adsorption of Zn on their surfaces. The speciation of Zn in soils was elucidated by extended X-ray absorption fine structure spectroscopy and microfocus X-ray fluorescence. The results obtained by linear combination fitting of EXAFS spectra revealed that the main forms of Zn in soil were outer-sphere Zn, Zn-illite, Zn-kaolinite, and HA-Zn. As the SOM content increased, the proportion of HA-Zn among the total immobilized Zn increased, and the proportion of nonspecific adsorbed Zn decreased. The present results implied that SOM is an important controlling factor for the environmental behavior of Zn in soils.

Silybin nanoparticles for liver cancer: development, optimization and in vitro - in vivo evaluation.

PURPOSE: Hepatocellular carcinoma (HCC) is a most common liver malignancy. The objective of this study was to prepare silybin nanoparticles (NPs) and optimize the prepared nanoparticles using central composite rotatable design-response surface methodology. METHODS: HCC was induced in rats by supplementing 100 mg/L of diethylnitrosamine (DENA) in drinking water for 8 weeks. Saline, silybin 30 mg/kg body weight and nanoformulation of silybin equivalent to silybin dose were administered orally to 3 groups of 6 animals each. Anticancer activity was evaluated by counting the liver nodules, and H & E staining analysis of tissue sections. RESULTS: The results showed that silybin NPs under optimized conditions gave rise to the entrapment efficiency (EE) of 88%, drug loading (DL) of 15%, mean diameter of 216 nm of the NPs prepared and zeta potential value of -15 mV. In rats treated with silybin NPs, the number of neoplastic nodules was significantly lower, the animals did not exhibit decrease in mean body weight, the number of liver nodules was reduced by >93% with significantly high localization in the liver. CONCLUSION: Orally administered silybin NPs showed improved efficacy and safety compared to silybin for the treatment of HCC in rats.

Synthesis, antitumor activity, and mechanism of action of 6-acrylic phenethyl ester-2-pyranone derivatives.

Based on the scaffolds of caffeic acid phenethyl ester (CAPE) as well as bioactive lactone-containing compounds, 6-acrylic phenethyl ester-2-pyranone derivatives were synthesized and evaluated against five tumor cell lines (HeLa, C6, MCF-7, A549, and HSC-2). Most of the new derivatives exhibited moderate to potent cytotoxic activity. Moreover, HeLa cell lines showed higher sensitivity to these compounds. In particular, compound showed potent cytotoxic activity (IC50 = 0.50-3.45 µM) against the five cell lines. Further investigation on the mechanism of action showed that induced apoptosis, arrested the cell cycle at G2/M phases in HeLa cells, and inhibited migration through disruption of the actin cytoskeleton. In addition, ADMET properties were also calculated in silico, and compound showed good ADMET properties with good absorption, low hepatotoxicity, and good solubility, and thus, could easily be bound to carrier proteins, without inhibition of CYP2D6. A structure-activity relationship (SAR) analysis indicated that compounds with ortho-substitution on the benzene ring exhibited obviously increased cytotoxic potency. This study indicated that compound is a promising compound as an antitumor agent.

[Association study of CNR1, GAD1 and BDNF polymorphisms with male heroin dependence in the Dai population in Yunnan].

In order to analyze the association of CNR1(Cannabinoid receptor 1), GAD1(Glutamate decarboxylase 1), and BDNF(Brain-derived neurotrophic factor) polymorphisms with male heroin dependence in the Dai population in Yunnan Province, an eight-SNP co-amplification protocol was established to genotype on the SNaPshot platform. A case-control study was performed with 8 SNPs from CNR1, GAD1, and BDNF genes in 165 heroin-dependent males and 170 healthy males of the Dai population. Statistical analyses were conducted with SPSS17.0, Haploview4.2, PHASE2.1, and MDR software. We found that: (1) the genotype frequency of rs13306221 was significant in the case group (P<0.025); (2) the A allelic frequency of rs6265 was significantly higher in the case group; (3) the haplotypes of T-A-C, C-C-C, C-C-T, and T-C-C based on rs1978340-rs3791878-rs11542313 and haplotype A-G based on rs6265-rs13306221 were significant (P<0.05); (4) the haplotype frequencies of T-A-C, C-C-T, and A-G were significantly higher in the case group. These results indicate that the linkage between rs1978340 and rs3791878 in GAD1 has a strong association with heroin dependence. Furthermore, polymorphisms in CNR1 (rs1049353), GAD1 (rs1978340 and rs11542313), and BDNF (rs6265 and rs13306221) were associated with heroin dependence in the Yunnan Dai population, and individuals with the rs6265 A allele were more likely to be heroin dependent.

Involvement and repair of epithelial barrier dysfunction in allergic diseases.

The epithelial barrier serves as a critical defense mechanism separating the human body from the external environment, fulfilling both physical and immune functions. This barrier plays a pivotal role in shielding the body from environmental risk factors such as allergens, pathogens, and pollutants. However, since the 19th century, the escalating threats posed by environmental pollution, global warming, heightened usage of industrial chemical products, and alterations in biodiversity have contributed to a noteworthy surge in allergic disease incidences. Notably, allergic diseases frequently exhibit dysfunction in the epithelial barrier. The proposed epithelial barrier hypothesis introduces a novel avenue for the prevention and treatment of allergic diseases. Despite increased attention to the role of barrier dysfunction in allergic disease development, numerous questions persist regarding the mechanisms underlying the disruption of normal barrier function. Consequently, this review aims to provide a comprehensive overview of the epithelial barrier's role in allergic diseases, encompassing influencing factors, assessment techniques, and repair methodologies. By doing so, it seeks to present innovative strategies for the prevention and treatment of allergic diseases.

ILC2s: Unraveling the innate immune orchestrators in allergic inflammation.

The prevalence rate of allergic diseases including asthma, atopic rhinitis (AR) and atopic dermatitis (AD) has been significantly increasing in recent decades due to environmental changes and social developments. With the study of innate lymphoid cells, the crucial role played by type 2 innate lymphoid cells (ILC2s) have been progressively unveiled in allergic diseases. ILC2s, which are a subset of innate lymphocytes initiate allergic responses. They respond swiftly during the onset of allergic reactions and produce type 2 cytokines, working in conjunction with T helper type 2 (Th2) cells to induce and sustain type 2 immune responses. The role of ILC2s represents an intriguing frontier in immunology; however, the intricate immune mechanisms of ILC2s in allergic responses remain relatively poorly understood. To gain a comphrehensive understanding of the research progress of ILC2, we summarize recent advances in ILC2s biology in pathologic allergic inflammation to inspire novel approaches for managing allergic diseases.

Safety and efficacy of endovascular treatment for acute ischemic stroke of large-vessel occlusion beyond the time window based on imaging evaluation.

PURPOSE: Endovascular treatment (EVT) of acute ischemic stroke caused by large-vessel occlusion (AIS-LVO) over 24 h of onset remains controversial. This study was to explore the safety and efficacy of EVT for patients with AIS-LVO between 24 and 72 h of symptom onset after rigorous imaging evaluation. METHODS: Patients with AIS-LVO treated with EVT were retrospectively enrolled and divided into two groups according to the time from symptom onset to groin puncture: 64 in the over-time group (>24 h) and 257 in the within-time group (≤24 h). Outcomes included 3-month modified Rankin Scale (mRS) score, functional independence (defined as mRS 0-2), successful cerebral reperfusion, symptomatic intracranial hemorrhage (sICH), and 3-month mortality. RESULTS: Patients in the over-time group had no significant differences in the functional independence (40.6% vs 42.5%, odds ratio or OR 0.91, 95% confidence interval or CI 0.52-1.60, p = 0.753), successful reperfusion (96.7% vs 95.8%, OR 0.76, 95% CI 0.36-1.59, p = 0.467), sICH (8.3% vs 6.7%, OR 1.20, 95% CI 0.42-3.38, p = 0.735), 3-month mortality (13.3% vs 10.8%, OR 1.17, 95% CI 0.51-2.70, p = 0.716) compared with patients in the within-time group. After matching adjustment, the results did not change significantly. CONCLUSIONS: The safety and effectiveness of EVT treatment for selected AIS-LVO patients with symptom onset of 24-72 h are not inferior to those treated within 6-24 h of onset, especially in a short term based on the pre-treatment advanced neuroimaging computed tomography perfusion even though further investigations are necessary to prove this finding.

Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV) with an average fatality rate of 12%. The clinical factors for death in SFTS patients remain unclear. METHODS: Clinical features and laboratory parameters were dynamically collected for 11 fatal and 48 non-fatal SFTS cases. Univariate logistic regression was used to evaluate the risk factors associated with death. RESULTS: Dynamic tracking of laboratory parameters revealed that during the initial fever stage, the viral load was comparable for the patients who survived as well as the ones that died. Then in the second stage when multi-organ dysfunction occurred, from 7-13 days after disease onset, the viral load decreased in survivors but it remained high in the patients that died. The key risk factors that contributed to patient death were elevated serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase fraction, as well as the appearance of CNS (central nervous system) symptoms, hemorrhagic manifestation, disseminated intravascular coagulation, and multi-organ failure. All clinical markers reverted to normal in the convalescent stage for SFTS patients who survived. CONCLUSIONS: We identified a period of 7-13 days after the onset of illness as the critical stage in SFTS progression. A sustained serum viral load may indicate that disease conditions will worsen and lead to death.